Professional Documents
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Nutrition Therapy For Chronic Kidney Disease-CRC Press (2012)
Nutrition Therapy For Chronic Kidney Disease-CRC Press (2012)
Therapy for
Chronic Kidney
Disease
Nutrition
Therapy for
Chronic Kidney
Disease
Edited by Lynn K. Thomas
Jennifer Bohnstadt Othersen
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Chapter 11 Nutrition for Children and Adolescents with Chronic Kidney Disease.................... 149
Peggy Solan
vii
viii Contents
Chapter 14 Chronic Kidney Disease and Mineral and Bone Disorder Management.................. 185
C.J. Parris and Beth Parris
Lynn K. Thomas
University of South Carolina School of Medicine
Columbia, South Carolina
Jennifer Othersen
WJB Dorn VA Medical Center
Columbia, South Carolina
ix
Editors
Dr. Lynn K. Thomas is the assistant dean for preclinical curriculum in the Office of Medical
Education and a clinical associate professor in the Department of Family and Preventive Medicine,
University of South Carolina School of Medicine. She also serves as the director of the Nutrition
Vertical Curriculum for the School of Medicine. She holds an associate degree in secondary educa-
tion from Shawnee State University; dual bachelors degrees in English and Dietetics plus a masters
degree in Home Economics/Nutrition from Marshall University; and a doctorate in Public Health
with an emphasis on nutrition education, from the University of South Carolina. She is a registered
dietitian, licensed in South Carolina, and a certified nutrition support clinician. Dr. Thomas has over
25 years of experience as a nutrition support and renal dietitian. She publishes in both the nutri-
tion and the education fields. In addition, she is a member of numerous professional organizations
including the American Dietetic Association, American Society of Parenteral and Enteral Nutrition,
and the National Kidney Foundation Council on Renal Nutrition.
Dr. Jennifer Othersen is the chief of the Division of Nephrology at the WJB Dorn VA Medical
Center in Columbia, South Carolina. She is also a DVAMC assistant professor of clinical inter-
nal medicine at the University of South Carolina. She earned a BS in biology at Francis Marion
University followed by a second BS in chemistry at the University of South Carolina. She holds an
MD from the Medical University of South Carolina where she also received her training in internal
medicine and nephrology. She is board certified in internal medicine and nephrology. She is active
in clinical research and is a principal investigator on several research studies currently being con-
ducted at the WJB Dorn VA Medical Center.
xi
Contributors
Nicole Armellino-Nitti Pranay Kathuria
Loyola University Medical Center Department of Medicine
Maywood, Illinois Division of Nephrology and Hypertension
School of Community Medicine
Malcolm L. Buford University of Oklahoma-Tulsa
Department of Medicine Tulsa, Oklahoma
Division of Nephrology and Hypertension
School of Community Medicine Anand Khurana
University of Oklahoma-Tulsa Department of Medicine
Tulsa, Oklahoma Division of Nephrology and Hypertension
School of Community Medicine
Tai-Gen Cui University of Oklahoma-Tulsa
Department of Nephrology Tulsa, Oklahoma
Beijing Chaoyang Hospital
Capital Medical University Fran Kittell
Beijing, China American Family Childrens Hospital
University of WisconsinMadison
Taixing Cui Madison, Wisconsin
Department of Cell Biology and Anatomy
University of South Carolina School of Jeannine C. Lawrence
Medicine College of Human Environmental Sciences
Columbia, South Carolina Department of Human Nutrition and
Hospitality Management
Charles J. Foulks University of Alabama
Department of Medicine Tuscaloosa, Alabama
Division of Nephrology and Hypertension
School of Community Medicine Emily Dill McDonald
University of Oklahoma-Tulsa WJB Dorn VA Medical Center
Tulsa, Oklahoma Columbia, South Carolina
xiii
xiv Contributors
CONTENTS
1.1 The Past..................................................................................................................................... 1
1.2 Early Understanding of Kidneys...............................................................................................3
1.3 More Discoveries.......................................................................................................................6
1.4 Urine..........................................................................................................................................8
1.5 Dialysis...................................................................................................................................... 9
1.6 Nutrition................................................................................................................................... 10
1.6.1 Diet and AKF.............................................................................................................. 11
1.6.2 Diet and Stage 4 CKD................................................................................................. 11
1.6.3 Diet and Stage 5 CKD................................................................................................. 12
1.6.3.1 Hemodialysis................................................................................................. 12
1.6.3.2 Peritoneal Dialysis........................................................................................ 12
1.7 Socialized Medicine................................................................................................................ 12
1.8 Summary................................................................................................................................. 12
References......................................................................................................................................... 12
1
2 Nutrition Therapy for Chronic Kidney Disease
FIGURE 1.1 Hippocrates (460377 BCE). (Courtesy of the National Library of Medicine.)
FIGURE 1.2 Early Greek medical practice. (Courtesy of the National Library of Medicine.)
Brief History of Kidney Disease 3
TABLE 1.1
Humors
Empedocless Hippocratess Hippocratess Hippocratess
Characteristics Elements Humors Seasons Organs
Bad temper Fire Yellow bile Summer Liver
Despondent Earth Black bile Autumn Brain/lungs
Calm Water Phlegm Winter Gall bladder
Hopeful Air Blood Spring Spleen
the belief that every living being contained certain mixtures of four humors (yellow bile, black
bile, phlegm, and blood). This belief was based on another popular theory, Essentialism, postu-
lated by Empedocles (495435 BCE), which described four material elements (air, earth, water, and
fire). The four material elements were controlled by forces called love and strife. The forces would
continuously act on the elements, which would be either held together by love or driven apart by
strife. The goal was to have both the elements and the forces in balance (Empedocles, 2010; Kirk
et al., 1983).
Hippocrates associated his idea of humoralism with the four elements and the four seasons
(Hippocratic Seasonal Diseases, 2010). He then related Empedocless balance theory to the humors.
A person in good health was considered eucrasic. An ill person was someone with an imbalance
of humors or dyscrasic. Hippocrates also linked the humors to body organs (Table 1.1). The use of
this system for diagnosis led the physicians to look for symptoms, or what is now known as doing
a clinical observation (Hippocratic Method and the Four Humors in Medicine, 2010). An example
is as follows: a fever was thought to be caused by too much blood in the body. This clinical obser-
vation led to the practice of bleeding the patient (Cataldi, 1998; Diamandopoulos et al., 2009;
Figures1.3 through 1.6).
Around the same time that Hippocrates was establishing scientific methods and describing
diseases, the Medical School of Knidos, Asia Minor, was concerning itself with the classification
of diseases by symptoms. In a book attributed to the school, About Inner Sufferings, four renal
diseases were classified first. Two descriptions that are considered accurate even today include
those of nephrolithiasis with renal colic and renal tuberculosis. The symptoms of the third disease
resemble those of possible renal vein thrombosis or bilateral papillary necrosis. The fourth dis-
ease corresponds to chronic suppurative renal infection or sexually transmitted urethritis (Dardioti
etal., 1997).
FIGURE 1.3 Black bile humor. (Courtesy of the National Library of Medicine.)
FIGURE 1.6 Yellow bile humor. (Courtesy of the National Library of Medicine.)
6 Nutrition Therapy for Chronic Kidney Disease
FIGURE 1.7 Claudius Galen (129214 CE). (Courtesy of the National Library of Medicine.)
the kidneys filtered urine. He instead determined that the kidneys attracted the depleted liquid
or urine (Galen, Translated by May, 1968; Figure 1.7).
For centuries, the gross anatomy of the kidneys was well documented. Leonardo da Vinci (1452
1519 CE) portrayed the anatomical features of the kidneys more accurately and artistically than
anyone before him. Unfortunately, he did not provide any new knowledge about the urinary system.
There continued to be little understanding of the functionality of the kidneys until the publication of
Opuscula Anatomica (1564 CE) by Bartolomeo Eustachio (Figure 1.8). He illustrated the kidneys in
47 copper-plated engravings and first described renal collecting ducts. Eustachio proposed that the
tiny ducts moved the urine from the kidney to the renal pelvis. He also described the adrenal glands
and the differing locations of the left and the right kidney (Mezzogiorno, 1999).
In 1662, Lorenzo Bellini (16431704 CE) suggested that small, intertwined masses in the kidney
were responsible for keeping urine separated from the blood. In 1666, at the University of Messina,
Sicily, Marcello Malpighi, a professor of medicine and founder of microscopic anatomy discipline,
was finally able to describe kidney histology and give physicians the first insight into the mecha-
nism of urine formation. He described the actual structure of the kidney, including the glomerulus
and the renal pyramids. Professor Malpighi utilized a microscope, made possible by the invention
of the lens, and two different staining techniques to identify the tubular structures and the vascular
tree (Andreucci, 1972; Eknoyan, 1996; Figure 1.9).
FIGURE 1.8 Depiction of urinary system in Opuscula Anatomica by Bartolomeo Eustachio. (Courtesy of
the National Library of Medicine.)
Capsular Pedicel
space
Podocyte Proximal
convoluted
tubule
FIGURE 1.10 Bowmans capsule. (From Shaun Riffle, University of South Carolina School of Medicine,
Columbia, SC. With permission.)
formed protective layers in the medullary and papillary collecting tubules and the duct of Bellini.
Henle assigned no function to the structures. Urine-formation principles were the subject of intense
debate during this period (Cataldi, 1998; Morel, 1999).
In 1842, William Bowman (18161892), a physiologist, investigated the relationship between the
glomerulus and the renal tubules. He studied thin slices of kidneys using the high-power micro-
scope of his days (300) and described the glomerular capillary tuft and its relation to the afferent
and efferent arterioles. He was the first to describe the basement membrane of the tubules and to
demonstrate the function of the capsules. He concluded that the glomerular capsule functioned as a
receptacle of filtrate separated from blood in the capillaries (Eknoyan, 1996; Todd and Bowman,
1856; Figure 1.10).
1.4 URINE
The work of Hippocrates in 400 BCE, Corpus Hippocraticum, contains approximately 400 apho-
risms that refer to the practice of medicine. Several of these describe how the urine reflects different
stages of renal disease.
When the urine is transparent and white, it is bad; it appears principally in cases of phrenitis.
Hippocrates (Section 4, Aphorsim 72 from Adams translation)
In those cases in which urine is thin at first, and the sediments become bilious, an acute disease is
indicated.
Hippocrates (Section 7, Aphorism 32 from Adams translation)
Diseases about the kidneys and bladder are cured with difficulty in old men.
Hippocrates (Section 6, Aphorism 6 from Adams translation)
Early Babylonian medicine also looked at urine as the diagnostic tool for kidney disease.
Markham Geller writes that the ancient physician consulted a list comprising statements such
as If his urine is like beer dregs, man suffers from discharge disease (Geller and Cohen, 1995).
Much later, Antoine Franois, comte de Fourcroy, a physician, and Louis Vauquelin, a pharmacist
and chemist, in the early nineteenth century completed the analysis of urine and for the first time
Brief History of Kidney Disease 9
Blood flow
Afferent Efferent
arteriole arteriole
1
Filtration
Renal corpuscle
2
Reabsorption
(solutes, water)
Nephron
Peritubular
capillaries
3
Renal tubule
Secretion
(additional wastes)
4
Excretion
noted the presence of nitrogen. They also were the first to surmise that urea overload could be
capable of causing diseases, and that urea was a toxin. In the second half of the nineteenth cen-
tury, further analytical studies concluded that potassium was the most toxic constituent of urine
(Richet, 1999).
The mechanism of urine formation remained controversial from the time of William Bowman in
1856. Scientists supported either the Filtration Theory or the Secretion Theory. Arthur Cushny
(18661926) proposed a unified, modern theory in 1916 and reported that urine was formed by
simple ultrafiltration in the glomeruli. By the mid-twentieth century, Alfred Richards (18761966)
established the theory of salt and water reabsorption. He was one of the pioneers who established
the true function of the kidneys (Morel, 1999; Figure 1.11).
1.5 DIALYSIS
Although nineteenth-century physicians and physiologists discerned the content and purpose of
urine, Thomas Graham, a Scottish chemist (18051869), was the first scientist to separate colloids
and crystalloids by using a dialyzer. His dialysis technique involved the separation of a mixture
of substances dissolved in a solution by passing the solution through semipermeable membranes
(Figure 1.12).
It may perhaps be allowed to me to apply the convenient term dialysis to the method of sepa-
ration by the method of diffusion through a system of gelatinous matter (Graham, 1854). The
word dialysis was not new to Graham. It was derived from Greek and means to part asunder.
However, he did provide its new meaning, which is still in use. His research earned him the name
father of modern dialysis.
Thomas Graham constructed several simple devices during his study of diffusion and dialysis.
His hoop dialyzer was made of gutta-percha and was closed on one end with parchment paper. The
hoop floated on the water surface in a large basin. Half a liter of urine, dialyzed for 24 hours, gave
10 Nutrition Therapy for Chronic Kidney Disease
Urine
Ox bladder
NaCl, Urea
FIGURE 1.12 Depiction of the Graham dialyzer. (From Shaun Riffle, University of South Carolina School
of Medicine, Columbia, SC. With permission.)
its crystalloid constituents to the external water. The latter, evaporated by a water bath yielded a
white saline mass. From this mass, urea was extracted ... Graham designed at least two other dia-
lyzers, a water-jar type and a bulb type. He fitted these with a variety of membranes. He studied the
effect of temperature and the efficacy of purification when using differing crystalloids. It was his
work and later that of John Abel (Baltimore in 1913), who developed the first artificial kidney, which
led to the current forms of hemodialysis treatment for kidney failure (Eknoyan, 2009; Graham,
1854; Gottschalk, 1998). Willem Kolff is considered the inventor of the first reliable artificial kid-
ney. His rotating drum artificial kidney, in 1943, offered an effective method of dialysis. Dr. Kolff
quickly put his artificial kidney into clinical use by successfully dialyzing a patient with acute kid-
ney failure (AKF) (Kolff, 1965).
Georg Ganter performed the first human peritoneal dialysis in 1923 (Teschner et al., 2004). This
type of dialysis was prone to complications and often failed secondary to peritoneum access issues.
Howard Frank, Arnold Seligman, and Jacob Fine at Bostons Beth-Israel Hospital established
more successful peritoneal treatments for AKF in 1946. A new stylet catheter made access to the
peritoneal cavity much easier and safer. Today, peritoneal dialysis, done at home, provides an alter-
native method to in-center hemodialysis.
Successful kidney transplants soon followed with the first successful transplant between identical
twins in 1954 (Boston). In 1962, cadaver transplants and the first use of antirejection drugs began
in Boston. The number of kidney transplants now exceeds 17,500 per year from both living related
and cadaveric donors (National Institute of Diabetes and Digestive and Kidney Diseases, 2010).
1.6 NUTRITION
The link between diet and declining kidney function came to prominence in mid-1800s when
Richard Bright suggested a milk diet to temporarily treat edema and proteinuria (Brights disease)
(Beebe, 1896). This type of extremely restricted diet was used well into the twentieth century
(Fahnestock, 1896). Fritz Bischoff (1932) conducted one of the first scientific examinations to
confirm the linkage between diet and kidney function. He used evidence from numerous studies
on animals to conclude that nephrotoxic factors could be a result of dietary intake. Several decades
Brief History of Kidney Disease 11
later, studies on humans confirmed his hypothesis (Maschio et al., 1982; Rosman et al., 1984). In
the interim, various practitioners proposed restricted diets to minimize uremic toxicity and delay
the loss of kidney function (Addis, 1948). Patients with either acute or chronic kidney disease
(CKD) were managed with a variety of diets that primarily limited sodium, protein, and fluids.
These therapeutic diets extended the lives of patients in a time when treatment options were almost
nonexistent (Addis et al., 1948).
TABLE 1.2
Borst Soup and Butterballs
Borst Soup Butterballs
Ingredients: Sugar 3/4 cup or ~150 g Ingredients: Powdered sugar 1/2 cup or 100 g
Unsalted butter 2/3 cup or ~150 g Unsalted butter 1/3 cup or ~80 g
Flour 12 tablespoons or ~20 g Vanilla extract 3/4 teaspoon
Water 11/4 cups or ~ 300 g Peppermint, lemon, or other flavorings (34 drops)
Mix all ingredients and heat slowly. Do not boil. Serve as Combine sugar and butter; add peppermint (optional).
soup. Divide into three servings Divide the mixture into 10 balls. Roll in powdered sugar.
~590 calories per serving with <1 g of protein Store in a freezer until use. ~100 kcal/ball. Low protein
12 Nutrition Therapy for Chronic Kidney Disease
1.8 SUMMARY
Future research holds the possibility of eliminating kidney disease. Until then, efforts would remain
focused on the prevention and/or control of illnesses that contribute to the decline of kidney function.
Dialysis techniques and equipment continue to be refined. Dialysis is becoming more portable
with new peritoneal techniques. Nutritional therapy, for now, is the key stone that can prevent and
control chronic renal diseases and make current dialysis techniques more effective.
REFERENCES
Adams, F., Translator. 1849. Hippocrates: Aphorisms. Online: http://classics.mit.edu/Hippocrates/aphorisms.
html (accessed July 29, 2010).
Addis, T. 1948. Mechanism of proteinuria. Science 108(2816):680.
Brief History of Kidney Disease 13
Addis, T., Gray, H., Barrett, E. 1948. Food protein consumption in glomerulonephritis: Effect on proteinuria
and concentration of serum protein. J Exp Med. 87(4):353368.
Andreucci, V. 1972. About the glomerulus. Kidney Int. 2: 349351.
Beebe, H. 1896. Brights disease. In Fisher, C., ed., Medical Century, Volume IV. New York: Medical Century
Company, 1719.
Bischoff, F. 1932. The influence of diet on renal and blood vessel changes. J Nutr. 5:431450.
Bloom, D. 1997. Hippocrates and urology: The first surgical subspecialty. Urology. 50:157159.
Borst, J. 1948. Protein katabolism in uraemia: Effects of protein free diet, infection, and blood transfusions.
Lancet. 1:824828.
Cataldi, L. 1998. The kidney through the ages. Proceeding of the 8th International Workshop of Neonatal
Nephrology. Rome, Italy.
Dardioti, V., Angelopoulos, N., Hajiconstantiou, V. 1997. Renal diseases in the Hippocratic era. Am J Nephrol.
17:214216.
Diamandopoulos, A., Goudas, P., Oreopoulous, D. 2009. Thirty-six Hippocratic aphorisms of nephrologic
interest. Am J Kidney Dis. 54:143153.
Dolan, J. and Adams-Smith, W. 1978. Health and Society: A Documentary History of Medicine. New York:
The Seabury Press.
Eknoyan, G. 1996. Sir William Bowman: His contributions to physiology and nephrology. Kidney Int.
50:21202128.
Eknoyan, G. 2009. The wonderful apparatus of John Jacob Abel called the artificial kidney. Semin Dial.
22:287296.
Empedocles. Online: http://plato.stanford.edu/entries/empedocles (accessed July 29, 2010).
Fahnestock, J. 1896. Hints on the general management and homeopathic treatment of chronic Brights disease.
In Fisher, C., ed., Medical Century, Volume IV. New York: Medical Century Company, 1417.
Galen, C. 1968. On the Usefulness of the Parts of the Body. Translated by Margaret Tallmadge May. Cornell
University Press. Google online books (accessed October 11, 2010).
Geller, M. and Cohen, S. 1995. Kidney and urinary tract disease in ancient Babylonia, with translations of the
cuneiform sources. Kidney Int. 47:18111815.
Giordano, C. 1963. Use of exogenous and endogenous urea for protein synthesis in normal and uremic subjects.
J Lab Clin Med. 62:231246.
Gottschalk, C. 1998. Thomas Graham, 18051869. Nephrology. 4:211216.
Graham, T. 1854. The Bakerian lecture on osmotic force. Philos Trans R Soc London. 144:177228.
Greek Medicine. Online: http://www.nlm.nih.gov/hmd/greek/greek_rationality.html (accessed July 24, 2010).
Hippocratic Method and the Four Humors in Medicine. Online: http://ancienthistory.about.com/cs/hippocrates/a/
hippocraticmeds.htm (accessed June 16, 2010).
Hippocratic Seasonal Diseases. Online: http://ancienthistory.about.com/od/greekmedicine/tp/062709Hippocra
ticSeasonalDiseases.htm (accessed June 18, 2010).
Kerr, D. 1973. Provision of services to patients with chronic uremia. Kidney Int. 3:197204.
Kirk, G., Raven, J., and Schofield, M. 1983. The Presoratic Philosophers, 2nd edition. Cambridge: Cambridge
Press.
Kolff, W. 1965. First clinical experience with the artificial kidney. Ann Intern Med. 62:608619.
Longrigg, J. 1993. Greek Rational Medicine. London and New York: Routledge.
Maschio, G., Oldrizzi, L., Tessitore, N., et al. 1982. Effects of dietary protein and phosphorus restriction on the
progression of early renal failure. Kidney Int. 22:371376.
Mezzogiorno, A. 1999. Bartolomeo Eustachio: A pioneer in the morphological studies of the kidney. Am J
Nephrol. 19:193198.
Morel, F. 1999. The loop of Henle, a turning point in the history of kidney physiology. Nephrol Dial Transpl.
14:25102515.
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). 2010. Kidney and Urologic
Diseases Statistics for the United States. Online: http://Kidney.niddk.nih.gov/Kudiseases/pubs/kustats
(accessed August 16, 2010).
Nissenson, A. and Rettig, R. 1999. Medicares End Stage Renal Disease Program: Current Status and
Future Prospects. People to People Health Foundation. Online: http://content.healthaffairs.org/cgi/
reprint/18/1/161.full.pdf+html (accessed August 16, 2010).
Rice Diet Program. Online: http://www.ricedietprogram.com (accessed August 3, 2010).
Richet, G. 1999. The contribution of French-speaking scientists to the origins of renal physiology and patho-
physiology (17901910). Am J Nephrol. 19(2):274.
Robson, J. 1969. Advances in the treatment of renal disease. Practitioner 203(216):483493.
14 Nutrition Therapy for Chronic Kidney Disease
Rose, W. and Wixom, W. 1955. The amino acid requirement of man. J Biol Chem. 17:9971004.
Rosman, J., Ter Wee, P., Meijer, S. 1984. Prospective randomized trial of early dietary protein restriction in
chronic renal failure. Lancet. 2:12911296.
Teschner, M., Heidland, A., Klassen, A., et al. 2004. Georg GanterA pioneer of peritoneal dialysis and his
tragic academic demise at the hand of the Nazi regime. J Nephrol. 17(3):457460.
Todd, R. and Bowman, W. 1856. The Physiological Anatomy and Physiology of Man, Volume II. London,
England: Parker.
Twardowski, Z. 2008. History of hemodialyzers. Hemodial Int. 12:173210.
2 Renal Physiology
L. Britt Wilson
University of South Carolina School of Medicine
CONTENTS
2.1 Overview of Function of Kidneys........................................................................................... 15
2.2 Structure/Function................................................................................................................... 16
2.3 Renal Hemodynamics.............................................................................................................. 18
2.4 Proximal Tubule......................................................................................................................20
2.5 Loop of Henle.......................................................................................................................... 22
2.6 Distal Tubule............................................................................................................................ 23
2.7 Collecting Ducts......................................................................................................................24
2.8 K+ Dynamics............................................................................................................................ 27
2.9 Integration and Pathophysiology.............................................................................................28
2.10 Summary................................................................................................................................. 29
References......................................................................................................................................... 30
15
16 Nutrition Therapy for Chronic Kidney Disease
Extracellular
Plasma
Na+low Cllow Na+high Clhigh
(vascular
K+high Ca2+low K+low Ca2+high space)
HCO3 low HCO3 high Red
blood
Intracellular Interstitial cells
Cell membrane
Blood
FIGURE 2.1 Schematic illustrating the major compartments of the body, relative distribution of water, and
relative concentrations of the more prominent electrolytes. Although the distribution of water andelectro-
lytes has been described for the interstitial compartment, the description applies to the extracellular com-
partment as well because the capillary membrane does not act as a barrier to water or the ions. See text for
more details.
two major compartments via osmosis. Ions, on the other hand, do not easily penetrate cells, and
thus a concentration gradient exists for the major ions. Of the more prevalent ions, the concentration
of free sodium (Na+), chloride (Cl), bicarbonate, and calcium (Ca2+)* is greater in the extracellular
compartment, whereas the concentration of free K+ is greater in the intracellular compartment. Na+
is the most abundant ion in the extracellular space, and its relatively poor permeability into the cell
means that it is the most abundant osmole of the extracellular compartment (Koeppen and Stanton,
2007; Rose and Post, 2001). The extracellular compartment is further subdivided into an interstitial
compartment and a vascular compartment, the latter comprising plasma and red cells (erythro-
cytes). These are separated by the capillary membrane, which serves as a barrier for large molecular
weight solutes (proteins, the most abundant in plasma being albumin) but does not exclude ions or
water (Koeppen and Stanton, 2007).
As mentioned above, the kidneys regulate extracellular volume and the extracellular electro-
lytes. The fascinating aspect is how they achieve this. Although more details are provided below,
in general, the kidneys achieve this in two basic ways. First, they regulate the extracellular volume
by regulating Na+. As is often said, where Na+ goes, water follows. Although not precise, this is a
good general rule of thumb to go by. Second, the kidneys regulate extracellular osmolality, and thus
the concentration of electrolytes, by regulating water. Recall that water affects the concentration of
solutes. Thus, by regulating water, the kidneys, at least in part, regulate extracellular electrolytes.
Although this is an oversimplification, if one keeps these two basic constructs in mind, it can greatly
facilitate ones ability to understand renal physiology.
2.2 STRUCTURE/FUNCTION
The nephron is the basic functional unit of the kidney, and Figure 2.2 is a schematic depicting the
basic anatomy of the nephron. It is essential to know this basic anatomy along with the nomen-
clature to understand renal physiology and pathophysiology. Blood enters the kidney via the renal
arteries (not depicted) and ultimately arrives at the glomerular capillaries (GC) via the afferent
* The Ca2+ difference here refers to free concentration. This does not take into account the intracellular stores of Ca2+.
Renal Physiology 17
AA
BS DT
PT MD
GC CCD
EA
ATL
DLH
ALH MCD
FIGURE 2.2 Basic drawing showing the fundamental anatomy of a nephron. Abbreviations are as fol-
lows: AA, afferent arteriole; EA, efferent arteriole; GC, glomerular capillary; BS, Bowmans space; PT,
proximal tubule; DLH, descending loop of Henle; ALH, ascending loop of Henle; ATL, ascending thick
limb (of loop of Henle); MD, macula densa; DT, distal tubule; CCD, cortical collecting duct; MCD, medul-
lary collecting duct.
arteriole (AA). Some of the plasma then filters into Bowmans space (BS). The blood exits the GC
via the efferent arteriole (EA) continuing into the peritubular or vasa recta capillary network (not
illustrated for clarity). Vasa recta are limited to the juxtamedullary nephrons, which comprise about
10% of the total number of nephrons (Eaton and Pooler, 2009; Koeppen and Stanton, 2007). The
venous drainage from these two capillary networks ultimately feeds into the renal vein and then into
the inferior vena cava. The AA and EA represent resistors in series, and changes in their tone affect
pressure in the GC, which in turn affects filtration. Filtration is the flux of fluid from the GC into
the BS. Granular cells of the AA synthesize and release renin and are part of the juxtaglomerular
apparatus. The macula densa (Figure 2.2) along with extraglomerular mesangial cells complete the
structural components of the juxtaglomerular apparatus.
The GC is leaky, meaning that it does not serve as a significant barrier to water and most of
the other constituents of the plasma. Electron microscopy shows large spaces (fenestrae) between
endothelial cells of the capillary endothelium, providing the anatomical basis for such leakiness
(see Figure 2.3). However, the GC is remarkably adept at excluding proteins from the BS, and an
electrostatic repulsion from the proteins lining the barrier is thought to be the mechanism for this
exclusion of plasma proteins (Eaton and Pooler, 2009; Koeppen and Stanton, 2007; Rose and Post,
2001). Appreciating this architecture is important for understanding renal pathology because altera-
tions in it form the basis for both nephritic and nephrotic syndromes (see Chapter 5). Minimal change
disease is one form of nephrotic syndrome in which extravasation of proteins occurs, but there are
no significant changes in the architecture of the GC or the Bowmans capsule (Alpers, 2005; Ix and
Lingappa, 2006).
As described many years ago by Starling, fluid flux across the capillary is primarily caused by
the hydrostatic and osmotic forces on both sides of the capillary (Eaton and Pooler, 2009; Koeppen
and Stanton, 2007; Rose and Post, 2001). For the kidneys, the forces in the GC and the BS are rel-
evant for filtration. Hydrostatic forces push the fluid away, and thus hydrostatic pressure in the
GC (PGC) promotes filtration. In contrast, hydrostatic pressure in the BS (PBS) impedes filtration.
Thus, the difference in the two plays an important role in determining the direction of fluid flux.
Under normal circumstances, PGC is much higher than PBS, hence fluid filters into BS. However, this
18 Nutrition Therapy for Chronic Kidney Disease
Podocyte
Bowmans
space
PFC PFC
Basal lamina
FIGURE 2.3 Electron micrograph showing the glomerular capillariesBowmans space (GCBS) interface.
Note the fenestrae or pores depicted by the arrows, creating a rather porous connection between the GC and
the BS. Podocyte foot processes (PFC) provide support for the basal lamina of the basement membrane and
contribute to the selective filtration of small solutes and water, but not plasma proteins. (Reproduced from
Marshall, S. Postgrad Med J., 80, 624633, 2004. With permission from BMJ Publishing Group Ltd.)
filtration can be reduced if PBS is elevated, as occurs in patients with kidney stones, pyelonephritis,
and polycystic kidney disease. Albumin is the key component for oncotic forces in the capillary, and
oncotic pressure in the GC (GC) retards filtration. Since proteins do not accumulate in the BS to
any significant degree, the oncotic force that would result is ignored. Thus, PGC is the driving force
for fluid filtration across the GC, whereas PBS and GC work against it. Under normal circumstances,
PGC exceeds the sum of PBS and GC, thus fluid filters through the GC into BS. However, as indicated
in the previous paragraph, alterations in the GC/BS junction (nephritic or nephrotic syndrome) can
markedly alter this fluid flux (Alpers, 2005; Ix and Lingappa, 2006).
The rate at which fluid filters into the BS is called glomerular filtration rate (GFR). In essence,
GFR represents the flow of protein-free fluid into BS and is an important marker of renal function.
The kidneys must filter blood to perform their function; hence, determining or estimating GFR
is considered an important first step in assessing the patient with suspected renal dysfunction.
Classically, GFR is measured using inulin, but there are formulas that one can use to estimate it
based, in part, on plasma creatinine, the rationale of which is as discussed below. Filtration, or
GFR, represents one of the four basic mechanisms (see Figure 2.4) utilized by the kidney. The
other three are reabsorption, which means the movement of water or solute from the tubule of the
nephron back into the peritubular or vasa recta capillaries; secretion, which is defined as move-
ment of solute from the capillary network surrounding the nephron into the tubule (note: this
means that the solute was not filtered); and excretion, defined as loss of water or solute from the
body via the urine.
Afferent Efferent
arteriole arteriole
Glomerular
capillaries
F
Bowmans
space
R
Peritubular capillaries/
S vasa recta
Excreted in
urine
FIGURE 2.4 Schematic illustrating the four fundamental processes of the kidney. These are as follows: F=
filtration, R=reabsorption, S=secretion, and E=excretion. See text for details.
R-AA R-EA
PGC
PPC
PGC-Pressure glomerular
AA-Afferent arteriole capillary
PPC-Pressure peritubular
EA-Efferent arteriole capillary
FIGURE 2.5 Simplified model showing the microcirculation of the nephron has two resistors and two capil-
lary beds in series. Note that the glomerular capillary is between the two resistors, that is, it is downstream
from the AA, but upstream of the EA.
simplified schematic depicting this. As a reminder, increasing resistance tends to decrease blood
flow, increase pressure upstream, and decrease pressure downstream. Decreasing resistance has
the opposite effect for all three. For example, if the AA vasoconstricts, then renal blood flow will
tend to fall and pressure upstream from the AA increases, whereas pressure downstream from the
AA decreases. Note that the GC is situated between the AA and the EA. Thus, constricting the
AA decreases PGC, whereas constricting the EA increases PGC, yet renal blood flow falls regard-
less of which one is constricted. Since PGC drives GFR, it decreases when the resistance upstream
increases, but GFR increases if resistance downstream (EA) increases. Understanding these princi-
ples has many clinical implications. For instance, stenosis of the renal artery will compromise blood
20 Nutrition Therapy for Chronic Kidney Disease
flow to the GC, and since the site of the stenosis is upstream from these capillaries, PGC and GFR
fall. Sympathetic stimulation can markedly constrict the AA (constricts EA also, but not as much),
which will decrease PGC and thus GFR. On the other hand, angiotensin II (AII) is considered to
preferentially constrict the EA (Jackson, 2006b; Rose and Post, 2001). Constriction of the EA causes
PGC to increase, with a resultant rise in GFR despite a fall in renal blood flow. Clinical data also
suggest that this is the case (Jackson, 2006b). If a patient, diabetic for example, has protein loss in
the urine, one way to reduce this protein excretion would be to reduce PGC. Angiotensin-converting
enzyme (ACE) inhibitors can often stop or reduce protein loss in the urine, because reducing AII
relaxes the EA, thereby dropping PGC (Marshall, 2004). However, one must recognize that GFR will
fall because of this drop in PGC.
The kidney is considered a good autoregulator. Autoregulation is the maintenance of a rel-
atively constant blood flow despite changes in driving pressure. Intrinsic myogenic mechanisms
participate as does tubular glomerular feedback (TGF). Delivery of sodium chloride to the macula
densa is thought to be the signal driving TGF. The theory is that the macula densa senses the
delivery of sodium chloride, and adenosine is released in proportion to the load of sodium chloride
delivered (Eaton and Pooler, 2009; Koeppen and Stanton, 2007). Adenosine is a potent vasocon-
strictor of the AA. Thus, increased delivery of sodium to the macula densa, such as would occur if
flow through the nephron increases, causes vasoconstriction of the AA with the resultant fall in PGC
and GFR. This ability to autoregulate blood flow allows the kidneys to autoregulate, in large part,
GFR. Although the kidneys do autoregulate well, renal blood flow can be compromised by stimula-
tion of the sympathetic nervous system. Strong sympathetic activation can markedly reduce renal
blood flow. Prostaglandins can also influence renal hemodynamics, but their role is subtle (Eaton
and Pooler, 2009; Koeppen and Stanton, 2007). There is very little evidence that prostaglandins are
important in the nonstressed state. However, vasodilator prostaglandins are released when renal
blood flow is reduced, for example, during elevated sympathetic activity. For this reason, blocking
prostaglandin production in stress states such as hemorrhage is often contraindicated. As mentioned
above, AII can influence renal hemodynamics, and the kidneys can synthesize AII locally (Koeppen
and Stanton, 2007).
FIGURE 2.6 Details of the major transport processes in the proximal tubule. See text for a more complete
description. The dashed line for water indicates its reabsorption follows the osmotic forces created by the
reabsorption of other solutes, primarily sodium.
water follows the solute, which results in diuresis. For this reason, uncontrolled diabetes can result
in significant diuresis since glucose is not reabsorbed completely. Mannitol is another example. It
is freely filtered, but not reabsorbed. Thus, this solute stays in the lumen of the nephron, so water
follows and diuresis results.
Phosphate (Pi) is another important solute that is cotransported with Na+ (Figure 2.6), and it
follows TM kinetics similar to glucose transport. About 80% of the filtered Pi is reabsorbed via this
transport mechanism. Parathyroid hormone (PTH) lowers the TM, which thus reduces Pi reabsorp-
tion in the proximal tubule (Eaton and Pooler, 2009; Koeppen and Stanton, 2007; Rose and Post,
2001). Patients with renal failure retain phosphate despite often having elevated levels of PTH (Rose
and Post, 2001). This likely reflects the loss of functioning nephrons rather than the inability of PTH
to effectively diminish the activity of this transporter. Regardless, plasma Pi levels represent an
important marker in patients with renal failure.
Bicarbonate is the most abundant base in the body, and approximately 80% of the filtered bicar-
bonate is reabsorbed in the proximal tubule (Eaton and Pooler, 2009; Koeppen and Stanton, 2007;
Rose and Post, 2001). However, note that bicarbonate is reabsorbed across the luminal membrane
as CO2 (Figure 2.6). Thus, the filtered bicarbonate combines with H+ to form CO2, and this reaction
is catalyzed by the carbonic anhydrase enzyme that exists on the luminal surface of the proximal
tubular epithelium. Inside the cell, the bicarbonate is reformed from the CO2 and exists on the
basolateral membrane to return to the blood. Given this, one should see that bicarbonate reabsorp-
tion is coupled to H+ availability and thus to H+ secretion by the proximal tubule cell. The cellular
concentration of H+ is thought to be the primary factor driving H+ secretion. Acidosis of the tubular
epithelial cells, therefore, increases H+ secretion and thus bicarbonate reabsorption. Reabsorbing
bicarbonate is adaptive in an acidotic condition since it is a base. On the other hand, alkalosis of
these cells decreases H+ secretion and bicarbonate reabsorption. Again, this is adaptive because
base is being eliminated from the body, thereby correcting alkalosis. This interplay illustrates one
mechanism by which the kidneys regulate bicarbonate and H+. Carbonic anhydrase inhibitors block
the luminal carbonic anhydrase, thereby reducing bicarbonate reabsorption. This results in diure-
sis (failure to reabsorb the osmole) and elimination of base from the body, hence the treatment for
22 Nutrition Therapy for Chronic Kidney Disease
respiratory alkalosis that occurs at high altitude. Finally, Fanconi syndrome is a genetic disorder in
which many of the transport processes in the proximal tubule are deficient (Koeppen and Stanton,
2007). One deficit is the ability of the proximal tubule to reabsorb bicarbonate. As a result of excess
loss of bicarbonate, the patient develops acidosis (type II renal tubular acidosis).
The other clinically relevant transport process in the proximal tubule involves organic acids
and bases, particularly organic acids (Eaton and Pooler, 2009; Koeppen and Stanton, 2007; Rose
and Post, 2001). The details of this transport are beyond the scope of this book, but in short, many
organic acids are reabsorbed in the proximal tubule. However, the basolateral membrane contains
transporters for organic acids, which are collectively called organic acid transporters (OATs).
These OATs secrete organic acids into the proximal tubule, and in turn, these organic acids are
secreted into the lumen of the nephron and eliminated via the urine. An important characteristic
of these OATs is that they are relatively nonselective. Thus, a variety of organic acids are secreted
via OATs, and therefore they compete for these transporters. This becomes particularly relevant
for pharmacotherapy because the administration of two drugs that are organic acids may alter the
pharmacokinetic profile of each drug, compared to the case when each was given in isolation.
Further, furosemide is an organic acid that requires OAT function to be delivered to its site of action
(El-Sheikh et al., 2008; Srimaroeng et al., 2008).
Uric acid is a particularly germane organic acid because of its role in gout. The renal handling of
uric acid is actually quite complex, and the details are beyond the scope of this book. In short, about
90% of the filtered uric acid is reabsorbed in the proximal tubule; OATs play a role in this, although
their precise role is controversial. Probenecid works on the kidney to increase the elimination of
uric acid (Burke et al., 2006).
Organic base transporters also exist in the proximal tubule of the nephron (Eaton and Pooler,
2009; Koeppen and Stanton, 2007; Rose and Post, 2001). The important physiological organic base
is creatinine. Creatinine is freely filtered but is not reabsorbed. Thus, what gets filtered gets elimi-
nated, and the clearance of creatinine is the primary route of elimination for creatinine. Because
of this, a fall in GFR causes a reduction in creatinine elimination and thus a rise in plasma creati-
nine. Therefore, plasma creatinine provides a rough marker for patients GFR and thus their overall
kidney function. However, the relationship between GFR and plasma creatinine is not linear. In
addition, the number of functioning nephrons declines with age. Further, the amount of muscle
mass and its breakdown can vary considerably from patient to patient. Thus, as indicated above, the
estimation of plasma creatinine is often plugged into a formula that takes into account patients age,
size, and gender. Finally, the proximal tubule secretes creatinine, and about 10% of the elimination
is tied to this secretion. Alterations in this protein-mediated transport could, at least in theory, alter
the level of plasma creatinine.
Capillary
Lumen of Interstitial
kidney tubule space
ATL epithelial cell
Na+ Na+
Na+ Na+ ATP
+
Cl Cl K K+
+ +
NH4 /K K+ NH4+
+ K+ H+ + NH3
Ca++
++
Mg
FIGURE 2.7 Schematic illustrating the Na+K+2Cl transporter in the ascending thick limb (ATL) of the
loop of Henle. See text for more details.
The critical transport process in the loop of Henle resides in the ascending thick limb (ATL),
a Na+ K+ 2Cl transporter (Figure 2.7). Approximately, one-quarter of the filtered Na+ gets
reabsorbed via this transporter (Eaton and Pooler, 2009; Koeppen and Stanton, 2007; Rose and
Post, 2001). This transport is electroneutral since two Cl ions move to balance the charge of
the two cations. However, the luminal membrane of these cells is relatively permeable to K+.
As a result, K+ can diffuse from the cell back into the lumen, thereby creating a lumen positive
potential. This potential helps drive Ca 2+ and Mg2+ reabsorption in the ATL via a paracellular
(between cells) pathway. About 25% of filtered Ca 2+ is reabsorbed in the ATL. In addition,
ammonium (NH4+) can substitute for K+ and move from the lumen into the epithelial cell.
Although not described in detail in this chapter, this ammonium can dissociate into ammonia
(NH3) and H+, and this ammonia in turn serves as the source that diffuses into the collecting
duct (see below).
The Na+K+2Cl transporter is the target for the loop diuretics (Eaton and Pooler, 2009; Koeppen
and Stanton, 2007; Rose and Post, 2001). Blocking this transporter reduces the reabsorption of not
only these three ions but also Ca2+ and Mg2+ because of reduced back diffusion of K+ described above.
Since several electrolytes are affected, loop diuretics can cause significant diuresis. Bartters syn-
drome is a rare genetic disorder, which has several variants (Eaton and Pooler, 2009; Koeppen and
Stanton, 2007; Rose and Post, 2001). However, in general, the syndrome is associated with a dimin-
ished function of the Na+K+2Cl transporter in the ATL. As one might predict, patients with this
syndrome typically present with low to normal blood pressure. As will be described later, they also
exhibit hypokalemia and alkalosis, which is most likely the result of elevated aldosterone (ALDO).
Capillary
Lumen of Interstitial
kidney tubule space
DT epithelial cell
PTH
FIGURE 2.8 The cells of the distal tubule (DT) contain a Na+Cl symporter and calcium channels. See
text for more details.
affecting renal transporters is Gitelmans syndrome. In this condition, there is a genetic deficit in the
DT Na+Cl transporter. Similar to patients with Bartters syndrome, these patients exhibit hypoka-
lemia and alkalosis, which is most likely the result of hyperaldosterone. However, unlike the patients
with Bartters syndrome, patients with Giltelmans syndrome have low urine Ca2+ (see below).
DT epithelial cells also express Ca2+ channels (Figure 2.8). Ca2+ follows its electrochemical gra-
dient into the epithelial cell via these channels, where Ca2+ is then shuttled back into the blood via
a basolateral Ca2+ATPase and a Na+Ca2+ antiporter. These channels are regulated by intracel-
lular cyclic adenosine monophosphate (cAMP), which is the second messenger for PTH. Thus,
PTH enhances Ca2+ reabsorption in the DT (Eaton and Pooler, 2009; Koeppen and Stanton, 2007;
Rose and Post, 2001). In addition, 1,25 dihdyroxycholecalciferol (active form of vitamin D) has a
permissive action on the renal reabsorption of Ca2+. Vitamin D induces the synthesis of calbindin,
a Ca2+-binding protein in the epithelial cells of the DT, which in turn binds intracellular free Ca2+
(Eaton and Pooler, 2009; Koeppen and Stanton, 2007; Rose and Post, 2001). This reduces the free
concentration of cytosolic Ca2+, thereby maintaining the concentration gradient needed for Ca2+ to
diffuse from the lumen into the cell, in turn, increasing Ca2+ reabsorption. This is a minor site of
action for vitamin D, with the cells of the duodenum being the main site.
The Na+Ca2+ antiporter may explain why thiazide diuretics often cause hypercalcemia (elevated
blood calcium). This transporter moves three Na+ in and one Ca2+ out (Figure 2.8). If Na+ uptake
via the Na+Cl transporter is reduced (mechanism of action for thiazide diuretic), this will reduce
intracellular Na+, which may in turn enhance the extrusion of Ca2+ from the cell since the Na+ gradi-
ent is enhanced. Likewise, this may be the mechanism by which patients with Gitelmans syndrome
have such low urine Ca2+.
Aldosterone Capillary
Lumen of Interstitial
kidney tubule space
+ Principal cell
Na+
Urea
Na+
Na+ Na+
H 2O ATP
K+ K
+
H2O High
cAMP osmolality
K+ GS
V2
AVP
FIGURE 2.9 The principal cells of the collecting duct reabsorb sodium via epithelial sodium channels
(ENaCs). Aldosterone exerts its primary effect on the principal cells, stimulating sodium reabsorption, which
in turn causes potassium secretion. The principal cells also contain aquaporins that allow water reabsorption
in the presence of AVP. Urea reabsorption is coupled to the reabsorption of water.
Principal cells are the target site for two of the three major hormones that target the kidney.
Specifically, these cells express receptors for ALDO and arginine vasopressin (AVP) [also called
antidiuretic hormone (ADH)]. The luminal membrane of the principal cells contains epithelial
sodium channels (ENaCs) (Figure 2.9). These channels are blocked by amiloride and are also
referred to as amiloride-sensitive sodium channels (Jackson, 2006a). Through these channels, Na+
follows its electrochemical gradient into the cell, where it is then pumped into the interstitium by the
Na+K+ ATPase. The amount of Na+ reabsorption is directly related to the Na+ gradient, as would be
predicted since Na+ reabsorption into the cell is via a channel. Thus, if the luminal concentration of
Na+ is elevated, then the reabsorption is elevated. However, this is a time-dependent phenomenon,
so if luminal flow is high, the overall percentage of Na+ reabsorption will be reduced.
Reabsorption of the cation Na+ causes K+ to leave the cell and enter into the lumen (Figure2.9).
The concentration gradient favors K+ secretion into the lumen (K+ high inside cell vs. luminal con-
centration), and the addition of the cation Na+ into the cells promotes K+ secretion by electrostatic
forces. In short, the salient feature to remember is that Na+ reabsorption drives K+ secretion. As
indicated, ENaC can be blocked by amiloride (Jackson, 2006a). This results in diuresis but K+ loss
is minimized because its secretion by the principal cells is coupled to Na+ reabsorption, and hence
amiloride and amiloride-like drugs are K+-sparing diuretics. ALDO also plays a pivotal role in
Na+ reabsorption in the principal cells. ALDO, a steroid hormone, increases the number of lumi-
nal ENaCs and enhances the activity of the basolateral Na+K+ ATPase (Eaton and Pooler, 2009;
Koeppen and Stanton, 2007; Rose and Post, 2001). Together, this can markedly increase Na+ reab-
sorption, which in turn increases K+ secretion. ALDO secretion is stimulated by plasma AII and K+,
the latter constituting a classic negative feedback pathway where hyperkalemia increases ALDO,
which increases renal K+ secretion, thereby reducing plasma K+. ALDO receptor blockers, such as
spironolactone, also serve as K+-sparing diuretics (Jackson, 2006a). Liddles syndrome is another
rare genetic alteration affecting the kidneys (Ix and Lingappa, 2006; Koeppen and Stanton, 2007;
Rose and Post, 2001). In this condition, genetic mutation of the ENaC results in enhanced Na+
reabsorption. Because Na+ reabsorption in the principal cells is markedly enhanced, these patients
present with hyperaldosterone symptoms such as hypertension and hypokalemia. However, renin
and, consequently, ALDO are markedly reduced.
26 Nutrition Therapy for Chronic Kidney Disease
The principal cells also express aquaporins, which are regulated by intracellular cAMP. AVP,
via the V2 receptor, stimulates adenylate cyclase, thereby increasing cAMP and allowing water to
pass through the luminal channels. Recall that the medullary interstitium has a high osmolality (see
Section 2.5). Thus, an osmotic gradient exists for water to move from the lumen into the intersti-
tium. Under normal conditions, this osmotic gradient always exists; thus, whether or not water is
reabsorbed is linked to circulating AVP levels. Not surprisingly, an important stimulus for AVP is
plasma osmolality, and AVP secretion is directly related to it. Thus, if plasma osmolality increases,
AVP increases, and water is reabsorbed by the kidney to reduce extracellular osmolality. If plasma
osmolality falls, AVP is inhibited, and water is excreted by the kidneys to bring osmolality back up.
In this way, the kidneys regulate extracellular osmolality.
Urea is also reabsorbed by the principal cells, and its reabsorption is linked to water (Eaton and
Pooler, 2009; Koeppen and Stanton, 2007; Rose and Post, 2001). When AVP is high, and hence water
reabsorption is high, the principal cells reabsorb urea with water. This reabsorption of urea is likely
the result of the increased luminal concentration of urea that occurs as water leaves the lumen. As
indicated above, urea constitutes about half the osmoles of the medullary interstitium, thus the reab-
sorption of this solute by the principal cells is the source of medullary urea. Urea then cycles within
the medullary interstitium, being secreted into the ascending loop of Henle and then reabsorbed by
the principal cells. This cycling provides the urea pool for the concentrated medullary interstitium.
Although urea cycles in this manner, it should not be interpreted that all of the urea load to the col-
lecting duct gets reabsorbed and cycled. In fact, about half the filtered load of urea is excreted, and
this elimination of urea is an important function of the kidneys. As has been well described, renal
failure causes urea retention; excess urea is toxic to the body, hence the term uremic poisoning.
Intercalated cells are the other cell type found in the collecting ducts. In short, intercalated cells
play an important role in acidbase regulation (Eaton and Pooler, 2009; Koeppen and Stanton,
2007; Rose and Post, 2001). The luminal membrane of intercalated cells (technically alpha-inter-
calated cells) contains H+ATPase and a H+K+ antiporter (Figure 2.10). Although not illustrated
in the figure, the secreted H+ can combine with bicarbonate to form CO2 in the same manner as
in the proximal tubule (see Section 2.4 and Figure 2.6). Thus, any bicarbonate remaining in the
tubule (although not described, ATL does reabsorb some bicarbonate) is typically reabsorbed in the
collecting duct. For those consuming a typical western diet, far more H+ is generated than can be
excreted as H+. Recall that pH is measure of free H+, and the luminal pH can only go so low before
it begins to damage tissues. Thus, the excess H+ must be excreted coupled to other compounds. The
two most important compounds are Pi (predominant titratable acid) and ammonia. As depicted
in Figure 2.10, H+ in the lumen can combine with Pi to form diprotonated Pi, which is excreted.
The secreted H+ can also combine with ammonia forming ammonium, which is not reabsorbed
and is thus excreted. The loss of H+ via ammonium accounts for the bulk of H+ excretion (about
two-thirds), and the kidneys synthesize ammonia in proximal tubule cells. Acidosis will stimulate
this renal synthesis of ammonia, which is quite adaptive. Note that for every H+ lost via diproton-
ated Pi or ammonium, a new bicarbonate ion is added to body stores (Figure 2.10). ALDO also
affects intercalated cells. This hormone stimulates H+ secretion into the lumen, although the precise
mechanism has not been well defined. Regardless, ALDO promotes H+ loss from the body.
The preceding paragraph illustrates that the kidneys are long-term regulators of H+ and bicarbon-
ate and thus are pivotal in acidbase regulation. The kidneys play a crucial role in compensating
for acidbase disturbances, and given the description above, one should be able to understand how
this is accomplished. For example, acidosis increases H+ secretion. This will enhance bicarbon-
ate reabsorption, thereby preserving the major base in the body. In addition, acidosis stimulates
ammonia synthesis, and the elevated H+ can be eliminated in greater quantities via its binding to
ammonia. Each H+ lost via ammonium creates new bicarbonate, thereby increasing base within the
body. On the flip side, renal dysfunction can cause acidbase disturbances. As mentioned, the kid-
neys must excrete significant quantities of H+. Thus, chronic renal failure is one cause of acidosis.
As mentioned above, failure to reabsorb bicarbonate in the proximal tubule results in type II renal
Renal Physiology 27
Capillary
Lumen of Interstitial
kidney tubule space
New
Alpha-intercalated bicarbonate
+ cell
K K+
HPO42
+
ATP HCO3 HCO3
H H+ +
H + HCO3 Cl
Cl
H+ H+
H2PO4 ATP
CA
NH3
+ H2O + CO2
NH4
Excreted in urine
FIGURE 2.10 Role of alpha-intercalated cells of the collecting duct in acidbase regulation. See text for
details.
tubular acidosis (e.g., Fanconi syndrome). Damage to the distal nephron (DT and collecting ducts),
by ischemia, for example, can impair the ability of the kidneys to excrete H+, resulting in type I renal
tubular acidosis. Type IV renal tubular acidosis is the result of inadequate ALDO (Ix and Lingappa,
2006; Rose and Post, 2001).
2.8 K+ DYNAMICS
Although the bulk of the body stores of K+ reside within the intracellular compartment, extracellular
K+ is kept within a very narrow range. Excitable tissue, particularly the heart, can be markedly altered
by changes in plasma K+, and fatal arrhythmias can result if K+ is not tightly regulated (Rose and Post,
2001). The kidneys play a pivotal role in this tight regulation of K+. A thorough description of whole-
body K+ regulation is beyond the scope of this book. Instead, we describe the four fundamental factors
that affect K+ secretion by the principal cells. These are as follows: (1)ALDO: As described above,
ALDO stimulates Na+ reabsorption, which in turn causes K+ secretion. Thus, there is a direct relation-
ship between ALDO and K+ secretion. This constitutes a negative feedback regulation because plasma
K+ concentration is one stimulus for ALDO. (2) Tubular flow: There is a direct relationship between
tubular flow and K+ secretion. As tubular flow increases, the concentration gradient for K+ between the
principal cells and the tubular lumen remains high; that is, there is not adequate time for K+ to accu-
mulate in the lumen, and thus more K+ moves from the cell into the lumen. This likely explains why
diuresis typically causes K+ loss. (3) Plasma K+: There is a direct relationship between the concentra-
tion of extracellular K+ and its secretion. First, higher extracellular K+ is thought to directly increase
the K+ concentration in the principal cells and thus increase its secretion. Second, elevated plasma K+
stimulates ALDO release, which also increases K+ secretion. (4) Acidbase disturbances: In general,
alkalosis increases K+ secretion, typically resulting in hypokalemia, whereas acidosis decreases (at
least initially) K+ secretion, resulting in hyperkalemia. There is evidence that H+ directly inhibits the
Na+K+ ATPase (Eaton and Pooler, 2009; Koeppen and Stanton, 2007). If so, then it follows that K+
secretion would fall in acidosis and rise in alkalosis (see Figure 2.9) because the basolateral Na+K+
ATPase affects not only K+ concentration inside the principal cells but also Na+ reabsorption. As
indicated, this is a generalization and an oversimplification since acidbase disturbances do not affect
only the principal cells of the body. Thus, it should be appreciated that the clinical presentation for K+
in acidbase disturbances can be quite varied from patient to patient.
28 Nutrition Therapy for Chronic Kidney Disease
The rise in extracellular osmolality stimulates AVP, which in turn causes the kidneys to conserve
water. Diabetes insipidus is the pathologic correlate of this condition (Else et al., 2006; Rose and
Post, 2001). In this condition, there is a lack of functional AVP because either AVP is not secreted
(central diabetes insipidus) or the kidneys fail to respond to the circulating levels of AVP (nephro-
genic diabetes insipidus). Regardless, the lack of AVP causes the kidneys to excrete water in excess.
This causes a rise in extracellular osmolality and a loss of water from cells (cellular dehydration).
Lithium can also have the negative consequence of producing a diabetes insipidus-like condition.
Lithium may alter the function of V2 receptors, thus causing marked water loss. In addition, lithium
can be nephrotoxic (Rose and Post, 2001). On the opposite end of the spectrum, one can consume
too much water, a condition called primary polydipsia. In this case, extracellular osmolality falls,
resulting in water moving into cells. To combat this, AVP levels fall, water reabsorption in the kid-
ney decreases, and the excess water is eliminated in an attempt to correct the reduced extracellular
osmolality. This process occurs even if there is no pathologic consumption of water, that is, simply
drinking water. The AVP pathology correlate is a syndrome of inappropriate ADH (SIADH). In
SIADH, there is excess AVP (Else et al., 2006; Rose and Post, 2001). This causes a pathologic
increase in water reabsorption with a concomitant fall in extracellular osmolality, causing water to
move intracellularly.
The second factor regulating AVP is blood pressure/volume. Both cardiopulmonary and arte-
rial baroreceptor stimulation inhibit AVP release (Abboud and Thames, 1983; Bishop et al., 1983;
Eaton and Pooler, 2009; Koeppen and Stanton, 2007; Rose and Post, 2001). Thus, a rise in arterial
blood pressure and/or intravascular volume decreases AVP, thereby causing water excretion and a
subsequent reduction in the extracellular volume. On the other hand, a drop in arterial blood pres-
sure and/or intravascular volume stimulates AVP release, causing water retention. In this regard,
AVP works in tandem with RAAS and thus plays some role in the overall regulation of the extra-
cellular volume. However, when AVP is considered alone, the process is self-limiting. If intravas-
cular volume falls, AVP increases, which in turn increases water reabsorption. Since this is water
alone, extracellular osmolality falls, which has a negative effect on AVP secretion. The opposite
occurs if arterial blood pressure and/or intravascular volume rises. Thus, significant and sustained
increases in the extracellular volume must occur using osmoles, for example, Na+ and thus RAAS.
Nevertheless, one should appreciate that severe intravascular volume loss, for example, hemorrhage,
can produce profound increases in AVP, which in turn can reduce overall osmolality.
2.10 SUMMARY
Understanding renal physiology is the backbone for understanding the clinical disturbances associ-
ated with renal dysfunction. The kidneys play a crucial role in regulating the extracellular compart-
ment. In this chapter, we reviewed the various transport mechanisms that exist in the nephron to
accomplish this feat. Via a countercurrent mechanism, a concentrated medullary interstitium of the
kidneys is created, and it is this concentrated interstitium that provides the osmotic driving force for
water reabsorption. In turn, AVP acts on the kidneys to regulate water reabsorption, thereby regulat-
ing overall extracellular osmolality. Not surprisingly, extracellular osmolality is an important regu-
lator of AVP secretion. The kidneys also serve as the mode of elimination for urea, a breakdown
product of protein metabolism, that exerts toxic effects on the body if it is not eliminated. In addi-
tion, the principal cells reabsorb Na+, and this reabsorption is primarily under the influence of the
hormone ALDO. Since Na+ is the predominant osmole of the extracellular compartment, regulating
this ion helps control the extracellular volume. Since the extracellular volume is an important com-
ponent of arterial blood pressure, the kidneys play a crucial role in long-term regulation of blood
pressure. One factor affecting ALDO release is plasma AII, and thus RAAS is a key player in blood
pressure regulation. In addition, ALDO stimulates K+ secretion, and plasma K+ is the second stimu-
lus for ALDO secretion. This forms a negative feedback loop to help tightly regulate extracellular
K+. Finally, the kidneys are long-term regulators of H+ and bicarbonate, and thus they play a pivotal
30 Nutrition Therapy for Chronic Kidney Disease
role in acidbase regulation of the body. Considering all this, it is not surprising that pathology of
the kidney can evoke multiple problems for a variety of organs, which underscores the important
role the kidneys play in whole-body homeostasis.
REFERENCES
Abboud, F. and Thames, M. 1983. Interaction of cardiovascular reflexes in circulatory control. In Shepherd,
J.T. and Abboud, F.M., eds., Handbook of Physiology. Baltimore, MD: American Physiological Society,
675753.
Alpers, C. 2005. The kidney. In Kumar, V., Abbas, A.K., and Fausto, N., eds., Pathologic Basis of Disease.
Philadelphia, PA: Elsevier Inc., 9551021.
Barrett, K., Barman, S., Boitano, S., et al. 2010. Renal physiology. In Barrett, K.E., Barman, S.M., Boitano, S.
and Brooks, H.L., eds., Ganongs Review of Medical Physiology. New York: McGraw-Hill Companies,
639686.
Bishop, V., Malliani, A., Thoren, P. 1983. Cardiac mechanoreceptors. In Shepherd, J.T. and Abboud, F.M., eds.,
Handbook of Physiology. Baltimore, MD: American Physiological Society, 675753.
Burke, A., Smyth, E., FitzGerald, G. 2006. Analgesicantipyretic and antiinflammatory agents: Pharmacotherapy
of gout. In Brunton, L.L., ed., Goodman and Gilmans the Pharmacological Basis of Therapeutics. New
York: McGraw-Hill Companies, 671715.
Dibona, G. 2002. Sympathetic nervous system and the kidney in hypertension. Curr Opin Nephrol Hypertens.
11:197200.
Eaton, D. and Pooler, J. 2009. Vanders Renal Physiology. New York: McGraw-Hill Companies.
El-Sheikh, A., Masereeuw, R., Russel, F. 2008. Mechanisms of renal anionic drug transport. Eur J Pharmacol.
585:245255.
Else, T., Hammer, G., Lingappa, V. 2006. Disorder of the hypothalamus and pituitary gland. In McPhee, S.J.
and Ganong, W.F., eds., Pathophysiology of Disease: An Introduction to Clinical Medicine. New York:
McGraw-Hill Companies, 456481.
Hoffman, B. 2006. Therapy of hypertension. In Brunton, L.L., ed., Goodman and Gilmans the Pharmacological
Basis of Therapeutics. New York: McGraw-Hill Companies, 845868.
Jackson, E. 2006a. Diuretics. In Brunton, L.L., ed., Goodman and Gilmans the Pharmacological Basis of
Therapeutics. New York: McGraw-Hill Companies, 737770.
Jackson, E. 2006b. Renin and angiotensin. In Brunton, L.L., ed., Goodman and Gilmans the Pharmacological
Basis of Therapeutics. New York: McGraw-Hill Companies, 789822.
Ix, J. and Lingappa, V. 2006. Renal disease. In McPhee, S.J. and Ganong, W.F., eds., Pathophysiology of
Disease: An Introduction to Clinical Medicine. New York: McGraw-Hill Companies, 456481.
Ganong, W. 2006. Cardiovascular disorders: Vascular disease. In McPhee, S.J. and Ganong, W.F., eds.
Pathophysiology of Disease: An Introduction to Clinical Medicine. New York: McGraw-Hill Companies,
300326.
Koeppen, B. and Stanton, B. 2007. Renal Physiology. Philadelphia, PA: Mosby Inc.
Kotchen, T. 2008. Hypertensive vascular disease. In Fauci, A.S., Braunwald, E., Kasper, D.L., Hauser, S.L.,
Longo, D.L., Jameson, J.L. and Loscalzo, J., eds. Harrisons Principles of Internal Medicine. New York:
McGraw-Hill Companies, 15491562.
Marshall, S. 2004. Recent advances in diabetic nephropathy. Postgrad Med J. 80:624633.
Rose, B. and Post, T. 2001. Clinical Physiology of AcidBase and Electrolyte Disorders. New York: McGraw-
Hill Companies.
Srimaroeng, C., Perry, J., Pritchard, J. 2008. Physiology, structure, and regulation of the cloned organic anion
transporters. Xenobiotica 38:889935.
3 Electrolyte and
AcidBase Disorders
Malcolm L. Buford and Charles J. Foulks
The University of Oklahoma-Tulsa
CONTENTS
3.1 Fluid and Electrolytes Introduction......................................................................................... 31
3.1.1 Sodium . ...................................................................................................................... 32
3.1.1.1 Hyponatremia............................................................................................... 32
3.1.1.2 Hypernatremia..............................................................................................34
3.1.2 Potassium.....................................................................................................................34
3.1.3 Calcium........................................................................................................................ 35
3.1.4 Phosphorus................................................................................................................... 37
3.1.5 Magnesium.................................................................................................................. 38
3.1.5.1 Hypomagnesemia and Hypermagnesemia................................................... 39
3.1.5.2 Recommendations.........................................................................................40
3.2 Trace Elements Introduction....................................................................................................40
3.2.1 Zinc.............................................................................................................................. 41
3.2.1.1 Zinc Metabolism........................................................................................... 41
3.2.1.2 Recommendations......................................................................................... 43
3.2.2 Selenium...................................................................................................................... 43
3.2.2.1 Selenium Metabolism................................................................................... 43
3.2.2.2 Recommendations.........................................................................................44
3.2.3 Copper.........................................................................................................................44
3.2.3.1 Metabolism...................................................................................................44
3.2.3.2 Recommendations......................................................................................... 45
3.2.4 Fluoride........................................................................................................................ 45
3.2.4.1 Metabolism................................................................................................... 45
3.2.5 Chromium....................................................................................................................46
3.2.5.1 Metabolism...................................................................................................46
3.2.6 Aluminum....................................................................................................................46
3.2.6.1 Metabolism...................................................................................................46
3.2.6.2 Recommendations......................................................................................... 48
3.3 Conclusion............................................................................................................................... 48
References......................................................................................................................................... 49
31
32 Nutrition Therapy for Chronic Kidney Disease
nutrition and electrolytes, which influence the management of these issues. This chapter provides the
reader with information about electrolytes from a systemic and pathophysiologic perspective.
3.1.1 Sodium
Sodium (Na+) is ubiquitous in nature and second to potassium in its distribution in the human body.
The average human body contains 9 oz (250 g) of sodium (Harvard, 2010). The roles of sodium in
the health of the individual are numerous and include maintaining normal plasma osmolality and
normal blood pressure, and nerve conduction (central, peripheral, and cardiac). In the kidney, sodium
also acts as a cotransporter for various elements, namely, potassium and phosphorus. Increased Na+
intake is a leading contributor to hypertension, second only to obesity. The average American diet
contains 3.4 g/d (d denotes day) of dietary sodium (roughly 1.5 teaspoons), and in other coun-
tries, dietary sodium intake is even higher (e.g., Finland has ranges of 711.2 g/d in men) (Charlton
et al., 2007). Due to the morbidity and mortality associated with chronic disease states such as
hypertension and atherosclerosis, in order to decrease the contribution to these diseases by dietary
discretion, the World Health Organization recommends limiting intake to <7 g/d in men and 6 g/d in
women, with the ideal intake being 4 g/d (Harvard, 2010). In United States, the Recommended Daily
Allowance (RDA) for sodium is 2.3 g/d if there is no associated medical illness and 1.5 g/d in the
presence of hypertension, CKD, or in persons of African American descent. To better define actual
dietary intake in hypertension that may be refractory to therapy utilizing 3+ agents, there should
be further evaluation by measuring 24-h urine collection for sodium excretion. Numerous studies
have shown a discrepancy between a patients reported dietary intake and actual urinary quantitative
excretion. This 24-h urine may be used to determine the actual dietary sodium or reveal the presence
of insidious sources of salt intake and help facilitate patient education.
There are several disease states in which sodium levels may rise or fall or where changes in
sodium levels may be a component of a larger disease process. As with all plasma electrolytes,
sodium levels are maintained within narrow limits, and the variation is divided into two groups,
hyper or elevated levels, hypo or depressed levels. Hypernatremia, defined as a serum Na+ > 145
mmol/L and hyponatremia, defined as serum Na+<135 mmol/L. The fluctuation of serum Na+ in
most cases actually reflects changes in volume status. It is imperative to note that serum Na+ levels
reflect free-water concentrations rather than an absolute abundance or deficit of total body sodium
content. Invariably, dietary Na+ is considered the culprit; however, this is rarely, if ever, the case. Table
3.1 depicts the typical differential of elevated Na+ levels, and Table 3.2 does the same for depressed
levels. In hyponatremia, it is customary to consider perceived volume status on examination of the
patient in addition to urinary Na+ concentration to help establish the source of the aberration.
3.1.1.1 Hyponatremia
Patients presenting with hyponatremia should first be evaluated by assessing their effective intravas-
cular volume. This is done by history and physical examination, obtaining vital signs such as ortho-
static blood pressures, and by laboratory evaluations such as for the fractional excretion of sodium
TABLE 3.1
HypernatremiaAssociated Disease States
High volume
Iatrogenic (hyperalimentation, hyperosmolar fluids)
Early diabetes insipidus
Low to normal volume
Dehydration (insensible loss, gastrointestinal, burns)
Late diabetes insipidus (nephrogenic or central)
Electrolyte and AcidBase Disorders 33
TABLE 3.2
HyponatremiaAssociated Disease States
Low volume states
Dehydration
Diuretic-induced (particularly thiazide diuretics, spironolactone)
Adrenocortical deficiency
Medication induced
Nausea/emesis prior to replacement fluids
Euvolemia (normal volume state)
Depression
Syndrome of inappropriate antidiuretic hormone (SIADH)
Acute kidney injury without volume overload
Fever
Pain
Acute psychosis
Pseudo hyponatremia
Pancreatitis
Nausea/emesis after inappropriate repletion
Excess volume states
Acute kidney injury
Chronic kidney disease
Congestive heart failure
Liver disease
(FeNa) and serum uric acid levels. In prerenal or underperfusing disease states, the FeNa will be <1%
unless there are compounding issues regarding kidney function or in patients on diuretics. The serum
uric acid level can provide clues to intravascular volume and renal perfusion. Hypovolemia can result
in elevated levels of antidiuretic hormone (ADH), which increases permeability of the distal tubule to
free water, resulting in dilution of measured serum Na+. Patients with decreased oral intake, nausea,
or emesis may show such findings. In this scenario, volume resuscitation with isotonic electrolyte
repletion would be appropriate. Hyponatremia with volume excess can also be present. Congestive
heart failure, liver disease or cirrhosis, and chronic renal disease are such scenarios. Patients may
have decreased peripheral perfusion pressures, thus increasing ADH and causing retention of free
water. This may occur despite the use of salt restriction and diuretics. A newer class of medications,
aquaporin channel inhibitors, are available and capable of indirect inhibition of the normal function
of vasopressin in the distal kidney and may be used to prevent the pathologic lowering of sodium
in the aforementioned disease states. There is currently no survival benefit for patients, and their
availability is still limited. Free-water restriction is typically recommended, as well as attempts to
provide adequate kidney perfusion pressure. A difficult situation arises when the patient is euvolemic
without an identifiable cause of low Na+. These patients should raise suspicion of the syndrome of
inappropriate antidiuretic hormone release (SIADH) after testing rules out other causes listed in
Table 3.2. Because of its association with malignant conditions, hyponatremia thought to be due to
SIADH should prompt exhaustive testing to find a source. In evaluating the patient with an unidenti-
fied source for hyponatremia, a thorough medication history should be obtained, including over-the-
counter medications and holistic/ritualistic medications as patients may omit these agents believing
them to be innocuous though the substances may be the causative agent.
Low-serum uric acid in patients with hyponatremia suggests volume excess with adequate distal
delivery and may serve to help differentiate SIADH from other causes of hyponatremia. Though
SIADH is placed in the euvolemic volume category, it is in fact a mildly volume-expanded disease
34 Nutrition Therapy for Chronic Kidney Disease
3.1.2 Potassium
Potassium (K+), the second element in our discussion, is a monovalent element similar to sodium and
is often found in the body working in conjunction with sodium. It is the most abundant cation in the
human body, with 2% in the extracellular compartment and 98% of body stores in the intracellular
areas. Typical serum concentrations of potassium are 3.55 mmol/L, and intracellular concentrations
are 125135 mmol/L (Rastergar et al., 2001; Wang et al., 1997). Typical daily intake of potassium
is 80120 mmol/d, and yet the body filters 700800 mmol/d in the urine, with the majority being
reabsorbed proximally in the kidney or in the limb of Henle. The majority of potassium loss from
the kidney occurs distally under the influence of aldosterone and sodium absorption at the epithe-
lial sodium channel. Potassium functions mainly in the maintenance of action potential gradients
because of its marked distribution difference and the ratio of that difference (Ki/Ke) (Rastergar et al.,
2001; Tang et al., 2004). Intracellular K+ is maintained by plasma NaK ATPase channels that are
phosphorylated to allow the exit of three molecules of sodium from the cell and then hydrolyzed to
allow the entry, via conformational change, of two molecules of potassium. Potassium contributes to
lacrimation, mucus in the lung, or surfactant elaboration and gastrointestinal (GI) peptide secretion.
In acute hypoxic events, K+ channels are inhibited resulting in large calcium influx into cells, particu-
larly carotid body chemoreceptors, inducing dopamine release, intense muscle cell contraction, and
vasoconstriction of responsive vessels (Tang et al., 2004; Wang et al., 1997; Weir and Rolfe, 2010).
Disorders of potassium are quite frequent, with hyperkalemia, defined as a serum K+ >5.5
mmol/L found in 5%10% of all patients with end-stage renal disease (ESRD), contributing to
2%5% of all deaths in patients on dialysis. Hyperkalemia causes 1.4% of all hospitalizations, with
levels >6.0mmol/L being particularly dangerous because it is at this level that cardiovascular con-
duction issues begin to be clinically relevant. Hypokalemia, defined as a serum concentration <3.5
mmol/L, is also associated with worsening hypertension, and in one study, K+ levels <4.0 mmol/L
were associated with increased mortality.
Signs and symptoms of clinical K+ irregularity are fairly similar in both elevated and suppressed
levels of potassium. Muscle weakness and potential paralysis are shared between the two extreme
levels. With hyperkalemia, there is usually a continuous spectrum of findings on electrocardiogram,
from initial peaked T waves with a normal to mildly prolonged PR interval to a finally widened
Electrolyte and AcidBase Disorders 35
QRS with prolonged duration and eventual sine-wave conduction with eventual failure and death.
These changes are not truly reflective of a particular level and can occur suddenly because of the
nature of potassium handling. See Tables 3.3 and 3.4.
Dietary recommendations for potassium in persons without risk for symptomatic hyperkalemia
are 4 g/d. This is roughly twice of what self-reporting instrument studies suggest persons in the
United States consume. Multiple sources of potassium are known, some of the more abundant ones
being legumes, fruits, and dairy products. Increasing K+ intake has shown to improve mortality,
lower blood pressure, and suppress progressive cardiovascular disease (CVD) and interstitial fibro-
sis in the kidney. However, patients with CKD are typically at high risk for developing hyperkalemia
because of the kidneys important role in potassium handling (Naito et al., 2010; Unwin et al., 2011).
3.1.3 Calcium
Calcium (Ca2+) is the fifth most abundant element in the body. In man, calcium in combination with
phosphorus helps to make up the mineralizing strength of the bone, where >99% of body calcium is
found (Peacock, 2010). Bone is composed of 70% mineral, 8% water, and 22% protein (in the form
of type I collagen) (Dawson-Hughes, 2003). Calcium is bound to plasma proteins such as albumin
and is free extracellularly in an ionized, physiologically active form to facilitate neurologic function
and muscular contraction. Intracellular systems utilize Ca2+, either free or bound to a protein called
calmodulin, to allow for hormonal signaling. Ca2+ is only available to humans through dietary gain,
although various mechanisms maintain physiologic ranges. The recommended intake for calcium
is 10001500 mg per day, of which 30% of the ingested amount is absorbed. This goal, however, is
rarely met, and numerous studies have been done or are currently underway with the goal of both
maximizing the education of the public about the importance of adequate dietary Ca2+ and encourag-
ing more fortification by the food industry.
The homeostatic mechanisms to maintain ideal ranges of calcium in the body (8.510 mg/dl)
are complex, and disturbances in them have the potential to cause disease in various organ sys-
tems. Three mechanisms maintain normal levels of calcium: intestinal absorption from dietary
TABLE 3.3
Causes of Hypokalemia
Renal losses
Medication
Renal tubular acidosis type I and II
Osmotic diuresis
Hyperaldosteronism
Liddles syndrome
Malnutrition
GI losses
Diarrhea
Laxative abuse
Consumptive loss
Malignancy
Refeeding
Transcellular shifta
Acid/base
Insulin administration
-receptor agonists
a Transient decrease.
36 Nutrition Therapy for Chronic Kidney Disease
TABLE 3.4
Causes of Hyperkalemia
Renal disease
Renal tubular acidosis type IV
Chronic interstitial disease
Decreased glomerular filtration rate
Gordons syndrome
Addisons disease (hypoaldosteronism)
Marked volume depletion
Tissue damage
Rhabdomyolysis
Chemotherapy with aggressive tumor
Medication
Nonsteroidal anti-inflammatory drugs
Potassium supplementation
Angiotensin-converting enzyme inhibitors
Angiotensin receptor blockers
-receptor blockers
Heparin
Transcellular shifta
Systemic acidosis
Hyperglycemia
a Transient.
intake, renal reabsorption, and bone turnover. To understand the balance of these systems, one
must look to the parathyroid hormone (PTH) and vitamin D metabolism. Beginning in the gut,
dietary Ca2+ absorption is facilitated by activated 1,25(OH)2 vitamin D, which when present
increases intestinal absorption and when absent decreases intestinal absorption. The absorption
of dietary Ca2+ is also affected by other ingested items such as oxalic acid or the presence of
phosphate, both of which form insoluble salts in the gut and result in the Ca2+ being excreted
in the feces (Taylor and Curhan, 2009). This can be minimized by diet planning if desired.
Increased absorption can be facilitated by supplementing the dietary Ca2+ with calcium supple-
ments. Historically, aluminum was utilized to bind phosphorus, but that has since fallen out of
favor, particularly in patients with severe kidney disease because of the risks of causing relatively
refractory anemia. After gut absorption, Ca2+ metabolism is also controlled by PTH. In the pres-
ence of increased PTH, the renal reabsorption of Ca2+ is increased in the proximal tubule cells,
and the hormone stimulates osteoclastic activity, increasing the liberation of Ca 2+ from bony
stores. Interestingly, the latter would concomitantly liberate phosphorus (P), but PTHs actions
in the proximal kidney counteract the accumulation of serum P in the presence of intact kidney
function by causing a P-wasting state. Recent evidence also shows that fibroblast growth factor 23
has a significant role in the functioning of vitamin D and renal handling of P, which can indirectly
also affect Ca2+ handling (Taylor and Curhan, 2009).
Numerous disease states affect calcium and its metabolism. In renal disease, the usual Ca2+
abnormality is hypocalcemia (serum levels < 8.5 mg/dL). This is typically due to diminished dietary
intake coupled with impaired 25-OH vitamin D activation with decreased 1a-hydroxylase activity.
Exogenous Ca2+ and vitamin D supplementation can be introduced to treat this hypocalcemia; if
hypocalcemia is not treated, adaptive mechanisms in the body will lead to decreased bone density
(renal osteodystrophy) as well as elevated PTH levels, resulting in secondary hyperparathyroid-
ism syndrome. This is important because the known association between elevated PTH levels and
Electrolyte and AcidBase Disorders 37
accelerated atherosclerosis may explain the higher incidence of heart disease and peripheral arte-
rial disease in patients with CKD. The two most common forms of hypercalcemia are not renal in
etiology: primary parathyroid adenoma in the outpatient setting and malignancy when previously
undiagnosed patients present to the hospital. See Tables 3.5 and 3.6.
3.1.4 Phosphorus
Phosphorus (P) is a multivalent element in the nitrogen family, which has great utility for normal
physiologic function. In nature, P is rather reactive and is never found as a lone element, but it
is always adjoined chemically in a compound, usually with oxygen. P has many different roles
both inside and outside the body. P is commonly found in fertilizers, detergents, and pesticides
(Isakova and Wolf, 2010). From a nutritional perspective, P is mainly found in dairy products,
meats, and fish. The RDA allowance for P is 7001250 mg/d depending on age and comorbidi-
ties such as pregnancy. In normal physiologic conditions, around 95% of dietary absorption is
excreted in the kidneys to maintain the normal serum concentration. Phosphorus is critical in
cellular membrane stability and generation of ATP within the Krebs cycle, and it plays signifi-
cant roles in intracellular hormonal action and tissue oxygenation via 2,3-BPG with hemoglobin.
The majority of P (~85%) is stored in bone alongside Ca 2+ as a salt called hydroxyapatite.P is
also typically found in food additives, consumption of which may play a rather significant role
in generating potentially harmful imbalances in most people.
TABLE 3.5
Causes of Hypocalcemia
Medications
Loop diuretics
Carbonic anhydrase inhibitors
Antiepileptics
Aggressive blood transfusion
Bartters syndrome
Malnutrition and refeeding syndrome
Secondary hyperparathyroidism
Vitamin D deficiency
Familial hypocalcaemia hypercalciuria
Post parathyroidectomy syndrome
TABLE 3.6
Causes of Hypercalcemia
Volume depletion
Malignancy
Multiple myeloma
Prostate cancer with lytic lesions
Parathyroid carcinoma
Medications
Thiazide diuretics
Gitelmans syndrome
Primary and tertiary hyperparathyroidism
38 Nutrition Therapy for Chronic Kidney Disease
Phosphorus homeostasis is maintained both by dietary intake and the feedback mechanisms in
the body that control vitamin D and PTH (Kalantar-Zadeh et al., 2010). In fact, aside from dietary
intake, the strict range of serum P in patients without clinical kidney dysfunction (2.54.5mg/dl)
is mostly mitigated through changes in how PTH affects P distribution. Upon ingestion of food, the
absorption of P averages between 40% and 80%, greatly influenced by PTH levels and the presence
of associated binders in the diet. For example, available Ca2+ and other phosphate-adherent mol-
ecules decrease systemic P absorption to the degree that has clinical utility. From a pathophysiologic
perspective, concerns about systemic P stem from several studies that have linked serum P levels to
advancing or accelerated atherosclerosis and CVD (Isakova and Wolf, 2010). Limiting phosphorous
intake has been shown to delay or decrease the rate of progressive atherosclerosis, particularly in
patients with chronic kidney disease. The challenge is maintaining healthy nitrogen/protein balance
in a diet while trying to minimize phosphorous ingestion. The K/DOQI guidelines (National Kidney
Foundation, 2003) recommend 1.2 g/kg/d dietary intake, and Shinaberger et al. found in follow-up
reanalysis of their patients that a slightly higher goal of 1.41.5 g/kg/d showed improved long-term
survival for patients on maintenance dialysis (Boaz and Smetana, 1996). The challenge stems from
the fact that the vast majority of easily available foodstuffs are laden with either high P/protein ratios
or are associated with inorganic P, which is more readily available for absorption from the gut and
hence systemically. Boaz and Smetana showed that dietary P was in fact an independent risk factor
for accelerated renal-function decline. Other authors have shown a measurable atherogenic potential
of these higher levels. The challenge therefore for patients and health care providers is education that
can help them make dietary choices that reflect our current understanding of P and its impact, at least
in renal disease, on CVD and long-term risk (Ix et al.,2009).
Several things may affect serum P levels (see Table 3.7). Aside from dietary change and the
above-mentioned roles of vitamin D, PTH, and calcium ingestion, other disease states may have
transient effects and must be kept in mind when approaching the patient with P levels outside of the
normal range, though with presumably normal kidney function. Assessment of the patients condi-
tion should help to identify complicating factors that may influence treatment decisions.
3.1.5 Magnesium
Magnesium (Mg) is the fourth most common cation found in humans, and it is abundant in the
environment. Fifty-two percent of the total body Mg is contained within bone, 27% in muscle, and
19% in soft tissues. Less than 1% of total body magnesium is present in the extracellular space.
Magnesium is required for many metabolic and enzymatic processes, including the synthesis of
nucleic acids and proteins, and in intermediary metabolism (Swaminathan, 2003). Hypomagnesemia
is much more common than hypermagnesemia, which is generally only seen in patients with kidney
TABLE 3.7
Disease States Associated with
Aberrant Phosphorus
Rhabdomyolysis
Burns
Acute or chronic renal failure
Hyperparathyroidism (PTH elevated in all)
Primary (low with elevated Ca2+)
Secondary (normal to high with low Ca2+)
Tertiary (high with elevated Ca2+)
Anorexia
Malignancy
Granulomatous disease
Electrolyte and AcidBase Disorders 39
dysfunction or those receiving a massive intake of Mg, generally given intravenously (e.g., the
eclamptic patient receiving magnesium sulfate). Magnesium is contained in food and water, and the
daily intake is dependent upon the Mg concentrations in these sources. Chlorophyll is magnesium
rich, and green leafy vegetables are excellent dietary sources. Magnesium is also found in nuts,
legumes, and grains. Other vegetables, fruits, meats, fish, and chocolates are not as Mg-rich, and
dairy products are Mg-poor. The Mg content of drinking water varies widely, and the Mg content
of hard water can be high. As long as dietary energy intake is not primarily obtained from sugar
and alcohol, the Mg intake roughly parallels the intake of energy. The Mg content of foods can be
markedly reduced (>85% loss) by boiling and refining or industrial processing of foods (Fawcett et
al., 1999). The current RDA for Mg is 4.5 mg/kg/d and is higher in pregnancy and lactation.
Many consuming a Western diet have an inadequate intake of Mg. About half of the Mg contained
in bone is exchangeable, and this acts as an Mg pool that can stabilize the serum Mg. The normal
range for serum Mg concentration is very narrow and is not affected by acidbase status. Magnesium
balance is a function of intake (absorption from food or medicine or intravenous administration) and
GI or renal conservation or loss. In persons who are exposed to a Mg-deficient diet, renal excretion
and GI excretion fall to 0.51.0 mEq/d each. Although the extracellular space contains little Mg, with
1/4 of the content within the intravascular space, the filtered load of Mg in the kidney is high. A 2.0
mEq/L serum Mg concentration in a person with a GFR of 120 mL/min (173L/d) will have a 24-h
Mg-filtered load of 346 mEq/d. The total body Mg of a 70-kg adult is about 2000 mEq. It is clear
that any impairment of renal conservation mechanisms can have rapid and potentially devastating
effects. Thirty percent of the serum Mg is protein bound and 70% is ultrafiltered by the glomerulus.
Over 95% of the filtered Mg is reabsorbed; of this, 20% is reabsorbed in the proximal tubule; 70%, in
the thick ascending limb of Henle; and the remainder is reabsorbed distally. Absorption in the thick
ascending limb is directly related to sodium chloride reabsorption and is inversely related to the rate
of urine flow. Diuretics increase urinary Na and urinary flow rate thereby increasing urinary Mg
losses and may lead to hypomagnesemia (Dai etal., 2001; Quamme, 1997).
GI absorption is inversely related to intake, and the majority of Mg is reabsorbed in the ileum
and cecum. PTH may be important in regulating Mg absorption, but the roles of vitamin D and
1,25(OH)2D are unclear. Dietary phytates bind Mg, but the low levels found in the usual diet are not
believed to impair absorption. Oxalate, phosphate, proteins, zinc, and potassium may affect absorp-
tion. The regulation of intracellular Mg is poorly understood. Less than 5% of intracellular Mg is
ionized; the remainder is bound to anionic compounds such as ATP, ADP, citrate, RNA, DNA, and
other proteins as well as being sequestered within the mitochondria and endoplasmic reticulum.
Different rates of Mg transport occur, with the highest transport rates being found in the heart, liver,
and kidney (Fawcett et al., 1999; Saris et al., 2000). Serum Mg is poorly reflective of the total body
Mg content (Rude, 1993). Although many measures of Mg exist, they are of no real clinical use. The
serum Mg remains the best measure available. When the serum Mg is low, intracellular Mg tends
to be low as well. Unfortunately, when the serum Mg is normal, the intracellular Mg may be low
(Fox etal., 2002; Whang et al., 1994). Patients with acute kidney injury (AKI) are unable to properly
secrete or reabsorb Mg secondary to primary renal damage to secretory and absorptive sites. Patients
with CKD have impaired Mg reabsorption due to tubular damage from diseases such as obstructive
uropathy, tubulointerstitial diseases, renal transplantation, tubular dysfunction caused by electro-
lyte disorders (prolonged hypokalemia) or mineral disorders (hypercalcemia), or inherited disorders
such as Bartters or Gitelmans syndromes. Certain drugs are known to cause renal Mg wasting, for
example, aminoglycosides and amphotericin, especially when used in prolonged courses of therapy
or in the presence of malignancies. Antineoplastic agents such as cisplatin are also associated with
renal Mg wasting as are some immunosuppressive agents such as cyclosporine (Lewis, 2009).
tremor. Carpopedal spasm in hypomagnesemia is generally seen when the patient has concomitant
hypocalcemia and hypokalemia. Generalized tonic-clonic seizures can be seen in young children
(Lewis, 2009). Mg concentrations < 1.0 mEq/L should be treated and intravenous Mg consid-
ered. Magnesium can be replaced orally or intravenously. Unfortunately, the oral intake of high
Mg-containing medications can result in diarrhea caused by the Mg load. Intravenous Mg is well
tolerated but can result in hypermagnesemia, especially when there is any degree of CKD. If
intravenous Mg is given, it must be closely monitored. Mg salts should, in general, be avoided
in patients with CKD, especially in CKD Stages 35. However, magnesium carbonate has been
used as a phosphate-binding agent, with 4% of the studied population developing diarrhea and 4%
developing hypermagnesemia (Tzanakis et al., 2008). Hypermagnesemia is characterized by mus-
cle weakness, respiratory depression, and cardiac dysrhythmias, especially Toursade de Pointes.
Although hypermagnesemia is defined as Mg > 2.1 mEq/L, these signs are not generally seen
unless the Mg is 23 normal. Intravenous calcium and volume expansion with NaCl solution
with a loop diuretic are treatments that can be used for severe or serious hypermagnesemia. In the
presence of AKI, CKD, or impaired urine output, hemodialysis (HD) may be required (Lewis,
2009).
3.1.5.2 Recommendations
Since most adult patients have multiple medical and surgical disorders and take multiple medica-
tions, serum Mg should be measured in any adult patient admitted to the hospital and should be
routinely followed in the outpatient clinic in patients who have diseases or who take medications
known to be associated with hypomagnesemia. Serum Mg should also be measured in all patients
with CKD Stages 35 since these patients may take many nonprescription drugs and supplements,
and nonrenal physicians sometime prescribe Mg-containing medications. Disorders of Mg should
be considered in patients who have altered or inadequate food intake, impaired absorption, renal or
GI losses, disorders associated with intercompartmental shifts, and in all patients who present or
develop hypokalemia.
Malnutrition is seen in many clinical circumstances and intracellular Mg deficiency must be
considered. Examples include patients with alcoholism; the homeless; the elderly; patients taking
multiple drugs; and patients with anorexia, severe depression, organic brain syndrome, decreased
mobility, inadequate resources to obtain or prepare foods, and unbalanced or nutritionally deficient
diets. Malnutrition is also caused by any disorder that interferes with intake, swallowing, digestion,
absorption, or processing and metabolism. Losses may occur in diarrheal illnesses and in renal
losses. Patients who have marginal total body Mg stores are at particular risk of developing severe
Mg deficiency when stressed by catabolic illnesses. Starved or malnourished patients when fed may
develop the refeeding syndrome and severe Mg deficiency can be seen. Mg-shifting occurs in dia-
betes mellitus, the refeeding syndrome, correction of acidosis, administration of sympathomimetic
amines, the hungry bone syndrome following parathyroidectomy, and in massive blood transfusion.
Renal Mg wasting can be caused by drugs such as aminoglycosides, amphotericin, and cisplatin as
well as being caused by Bartters or Gitelmans syndromes (Swaminathan, 2003).
Hypermagnesemia is seen in patients with AKI or CKD who have been given or who have
ingested Mg-containing medications. It can also be seen in patients who have been given large intra-
venous doses of Mg. Treatment involves the use of intravenous calcium, NaCl volume expansion
and loop diuretics, or emergency HD.
arsenic (As), aluminum (Al), lithium (Li), tin (Sn), lead (Pb), and mercury (Hg). Some of these ele-
ments such as Al, Li, and Pb accumulate in the body as glomerular filtration rate (GFR) falls, leading
to increased tissue burdens that cause disease. Even with a normal GFR, Li and Pb can accumulate
in persons exposed to high amounts, such as those living close to a lead smelter. Other elements, such
as As and Hg, are toxic and lead to serious and often fatal disorders. The importance of Mo in the
activity of xanthine oxidase, sulfite oxidase, and aldehyde oxidase is known, but deficiency is exceed-
ingly rare and toxicity nearly nonexistent (Johnson, 2008c). Although there are no data on the use of
weight-reduction diets in patients with CKD or ESRD, it is concerning that a recent publication has
shown that each of four popular weight-loss diets was insufficient in the minimum Reference Daily
Intake (RDI) for 27 micronutrients. Six micronutrients were consistently low in all diets: vitamin B7,
vitamin D, vitamin E, Cr, I, and Mo (Calton, 2010). The impact of using these diets for weight loss
in obese adults with CKD should cause concern and clinicians should monitor the use of these diets
closely. In this chapter, we will focus on the metabolism of Zn, Se, Cu, F, Cr, and Al.
3.2.1 Zinc
3.2.1.1 Zinc Metabolism
Zinc (Zn) is an essential TE that is involved in numerous aspects of cellular metabolism. Zn sup-
ports normal growth and development, is active in immune function, protein synthesis, and wound
healing (Fabris and Mocchegiani, 1995; Heyneman, 1996; Institute of Medicine, 2001; Maret and
Sandstead, 2006; Prasad, 1995; Simmer and Thompson, 1985; Solomons, 1998). Zn is also required
for proper sense of taste and smell (Prasad et al., 1997). Zn is necessary for the proper transcrip-
tional control of specific genes associated with cellular proliferation and differentiation as well as
intracellular signaling (Cousins, 1996). Zn is primarily found in teeth, hair, skin, bones, liver, mus-
cles, leucocytes, and the testes, and over 80% of blood Zn is found in carbonic anhydrase, essential
in acidbase balance (Linder, 1991).
A daily intake of Zn is required to maintain a steady state because the body has no specialized
Zn storage system. Whole grains and milk products are good sources of Zn, and many ready-to-
eat breakfast cereals are fortified with Zn. Oysters, red meat, and poultry are excellent sources
of Zn, as are baked beans, chickpeas, and nuts (such as cashews and almonds) (Office of Dietary
Supplements, 2009). Phytates (whole-grain breads, cereals, legumes, primarily) bind Zn and inhibit
its absorption (Sandstrom, 1997; Solomons, 1998; Wise, 1995). Thus, the bioavailability of Zn from
grains and plant foods is lower than that from animal foods, although many grain- and plant-based
foods are still good sources of Zn.
Zn deficiency in the United States is seen only when there is insufficient intake, increased loss, or
an increased requirement (Hambidge, 1989; Institute of Medicine, 2001; King and Cousins, 2005;
Prasad, 1996). Insufficient intake is seen in those with marginal diets such as the elderly, the home-
less, or those with alcoholism (Institute of Medicine, 2001; Menzano and Carlen, 1994; Navarro etal.,
1994). Vegetarians are at particular risk of inadequate Zn intake not only because meat is higher
in Zn than nonmeat foods but also because the vegetarian diet is high in legume and grain intake.
Vegetarians can overcome some of the phytate binding by soaking or dialyzing the grains or legumes
in water for several hours prior to intake and by using grains in leavened products since the leaven-
ing process breaks down phytates (American Dietetic Association, Dietitians of Canada, 2003; Hunt,
2003). Other persons at risk of Zn deficiency include those with GI diseases such as malabsorption
syndromes, inflammatory bowel disease, and short bowel syndromes in which there is an increased GI
loss, or renal wasting of Zn such as patients with AKI or CKD and persons who may have increased
requirements for Zn (Hambidge, 1989; Solomons, 1998; Valberg et al., 1986). Decreased Zn can also
be seen in patients with chronic liver disease, CKD, diabetes mellitus, sickle cell disease, in women
who are pregnant or lactating, and in older infants who are exclusively breast-fed (Caulfield et al.,
1998; Krebs, 1998; Solomons, 1998).
42 Nutrition Therapy for Chronic Kidney Disease
3.2.1.2 Recommendations
Patients with CKD who are on restricted diets or being treated with conservative therapy should
have their Zn levels determined on whole blood samples if there is a concern that malnourishment
is present or may develop. Whole-blood Zn should be measured in patients with CKD with GI
diseases that affect food intake or proper absorption lasting more than 12 weeks. If the patient is
already malnourished, Zn levels should be measured. If the Zn level is low, short-term Zn supple-
mentation should be considered until the patient has returned to an acceptable and stable clinical
status.
Zn levels should be measured in patients on dialysis who develop malnutrition or anorexia, and
if the disorder is prolonged over 12 weeks, Zn supplementation should be considered. Patients who
are malnourished when they begin dialysis should have their Zn measured if the malnutrition does
not improve after 1 month of adequate dialysis. Patients with CKD who have dysgeusia that is not
due to medications, inadequate dialysis, or readily reversible illness (e.g., sinusitis) should have their
Zn checked, and they should be treated for 46 weeks to determine if there is a clinical response. Zn
supplementation should be considered in malnourished patients with CKD or on dialysis who are
hospitalized, especially if they have a prolonged illness that interferes with food intake or absorp-
tion or if the patients catabolic rate is high. Hospitalized patients with CKD or ESRD who are
receiving total parenteral nutrition (TPN) or peripheral parenteral nutrition (PPN) should have TE
added to the TPN; however, the amount needed is unknown. It is generally thought that TE solution
should be given 23 times weekly. It may be better to also follow the whole blood Zn level and to
add supplemental Zn to the TPN or PPN solution. TE solution for TPN can also be used to provide
TE to patients receiving enteral feedings who are TE deficient.
3.2.2 Selenium
3.2.2.1 Selenium Metabolism
Selenium (Se) in the diet comes from two Se-containing amino acids: selenocysteine and sele-
nomethionine (Burk and Levander, 1999). Dietary sources of these two amino acids are various
seafoods, kidney, liver, and meat. Grains may also contain appreciable amounts of Se, although
this depends on the Se content of the soil (10th Edition of the RDAs, 1989b). Dietary Se is highly
bioavailable. Se is active in glutathione peroxidase, which metabolizes hydroperoxides formed
from polyunsaturated fatty acids, and it is also active in enzymes that deiodinate thyroid hormones
(Johnson, 2008d).
The methionine absorptive pathways in the small intestines are responsible for Se absorption
(Burk and Levander, 1999) Inorganic Se (dietary supplements) is passively absorbed in the duode-
num, and Se absorption appears to be unregulated (Thomas and Robinson, 1993). There is no storage
pool for Se; however, the incorporation of Se-methionine into amino acids serves the same pur-
pose. Se-cysteine is absorbed directly from foodstuffs and is also metabolized from Se-methionine
(Thomas and Robinson, 1993). It can also be synthesized from Se replacement of oxygen residue
on serine while serine is bound to a specific tRNA (Burk and Levander, 1996). Se is released when
Se-cysteine and Se-methionine are catabolized. Se is excreted in the urine.
The typical Se intake in the United States is 100250 mcg/d; whereas in Finland and New
Zealand, it is 3050 mcg/d. Despite this broad range of intake, Se deficiency is rare (Johnson,
2008d). Muscle weakness and cardiomyopathy, impaired immune function, macrocytosis, and
white nail beds are associated with and seen in Se deficiency (Hawkes et al., 1996; Rayman,
2000). In certain areas of China, where Se intake can be as low as 10 mcg/d, an endemic cardio-
myopathy that affects children and women of childbearing age can been seen, which improves
with Se supplementation. Se supplementation can prevent Keshan Disease (cardiomyopathy
caused by Se deficiency) (Johnson, 2008d). High intakes of Se can be toxic, causing hair loss,
the formation of abnormal fingernails and toenails, dermatitis, peripheral neuropathy, nausea,
44 Nutrition Therapy for Chronic Kidney Disease
diarrhea, fatigue, irritability, or halitosis (imparting a garlic odor to the breath). However, there
is no good definition of toxic Se blood levels (Johnson,2008d).
Se levels are lower in HD patients than in the general population (Tonelli et al., 2009). Plasma
Se concentrations and erythrocyte glutathione peroxidase activity are strongly correlated, and glu-
tathione peroxidase activity increases with Se supplementation (Koenig et al., 1997; Saint-Georges
etal., 1989). There is greater decrease in serum and platelet Se in dialyzed patients with CVD than
in those without (Girelli et al., 1993). However, Se supplementation in patients with low Se concen-
trations did not improve echocardiographical parameters of left ventricular function or morphology
(Maher et al., 1987). Low Se levels and abnormal thyroid function abnormalities are frequently seen
in dialyzed patients (Napolitano et al., 1996). Uremic patients who received selenium supplemen-
tation demonstrated increased T-cell response to phytohemagglutinin and increased delayed-type
hypersensitivity (Bonomini et al., 1995).
3.2.2.2 Recommendations
The manifestations of Se deficiency mimic the findings in patients with advanced CKD and patients
with ESRD who are receiving dialysis therapy. It is impossible to distinguish between disorders
caused by CKD or other comorbid conditions and those potentially caused by Se. Since Se defi-
ciency syndromes do not occur in the United States in patients who have access to food, they should
not be considered unless the patient has a reason to have inadequate intake of food or normal
absorption of food. Since we do not know how long it takes for Se-cysteine and Se-methionine
stores to become depleted, we do not know how long it takes to become Se deficient in the face of
inadequate Se intake. It seems reasonable to follow the Clinical Guidelines of the American Society
for Parenteral and Enteral Nutrition: Nutritional Support in Adult Acute and Chronic Renal Failure
(ASPEN, 2011). Se intoxication is extremely rare and should only be considered in patients who are
receiving Se supplementation.
3.2.3 Copper
3.2.3.1 Metabolism
Virtually all copper (Cu) in the human is bound to body proteins, since free or unbound Cu is
highly toxic. Cu metabolism is highly controlled both by genetic mechanisms that regulate the
incorporation of Cu into apoproteins and by processes that prevent toxic Cu accumulation. As long
as the genetic mechanisms that control Cu metabolism are normal, Cu deficiency rarely occurs.
It is seen in severe, long-standing Kwashiorkor; persistent infantile diarrhea, typically in a child
whose diet is limited to milk; severe malabsorption syndromes, and excessive Zn intake (Johnson,
2008b).
Cu is abundant in vegetable products, grains, legumes, seeds, and meat, in that order. Of all foods,
liver contains the highest concentration of Cu (Johnson and Kays, 1990). After being absorbed in
the proximal small intestine, Cu is bound to albumin and amino acids. Transcuprin, a specific Cu
transporter may be involved. The majority of the Cu is taken up by the liver on the first pass. Once in
the liver, Cu is incorporated into ceruloplasmin, a protein that acts as the transfer agent for moving
Cu from the liver to the peripheral tissues. Ceruloplasmin also plays a role in Fe metabolism, serv-
ing as a plasma ferroxidase. Methionone may act as a Cu storage protein (Chan and Rennert, 1980;
Harris, 1995). All Cu excretion occurs through the GI tract, with bile excretion accounting for half.
The exception is the loss of ceruloplasmin in the urine in nephritic syndrome, causing a decrease in
serum Cu levels (Stec et al., 1990).
Biological roles for Cu include incorporation into several important Cu-containing enzymes
including ZnCu superoxide dismutase (antioxidant defense), dopamine mono-oxygenase
(neurotransmitter synthesis), lysyl oxidase (collagen cross-linking, bone formation), ceruloplasmin
(Cu transport and ferroxidase), cytochrome c oxidase (electron transport), factor V (hemostasis),
and tyrosinase (melatonin production) (Danks, 1988; Lutsenko, 2010).
Electrolyte and AcidBase Disorders 45
Cu deficiency is unusual in the absence of genetic disorders and is mostly seen in premature
babies receiving milk formulas, patients with chronic diarrhea (or malabsorption syndromes), gas-
trectomy, Roux-en-Y gastric bypass surgery, patients receiving chronic parenteral nutrition without
TE supplementation, patients on prolonged oral Zn supplementation or patients who have ingested
Zn-containing coin(s) (Zn and Cu are competitively absorbed in the jejunum), and patients on chronic
peritoneal dialysis. Cu deficiency is marked by skin depigmentation, fragile and kinky hair, weakness,
edema, hepatosplenomegaly, osteoporosis, and neurological abnormalities such as ataxia, neuropathy,
and cognitive defects that closely mimic vitamin B12 deficiency (Fleming, 1989; Griffith et al., 2009;
Juhasz-Pocsine et al., 2007; Kumar et al., 2004; Shaw, 1992; Tan et al., 2006). Menkes disease is a
congenital x-linked genetic disorder that is caused by a mutation in the intestinal transport protein for
Cu. The severe Cu deficiency leads to profound neurological deterioration and death in early child-
hood. The involved gene is closely linked to the gene responsible for Wilsons disease (Danks, 1988).
Wilsons disease is an autosomal recessive disorder characterized by excessive Cu accumulation.
It is caused by a mutation in a Cu-ATPase enzyme that is closely related to the gene defect in Menkes
disease. Many tissues are involved in Cu overload deposition leading to cardiac dysfunction (congestive
heart failure, rhythm disturbances), hepatic cirrhosis, diabetes mellitus, renal failure, and malignancies
(Harris, 2000; Linder, 1996). Wilsons disease is treated with a low-Cu diet and the use of a Cu chelating
agent. Oral Zn may be used early in the course of the disease since it is a competitor ofGI absorption.
Cu levels (plasma and serum) have been reported to be normal to high in patients with renal
failure, but levels have been reported to be low in patients treated with HD or PD (Borner et al.,
1984; Hasanolu et al., 1994; Hosokawa et al., 1985; Picchota et al., 1983; Thomson et al., 1983). The
increased Cu found in some patients is not accompanied by an increase in plasma ceruloplasmin.
The cause of the delinking of this relationship is unknown (Sondheimer et al., 1988). Hemo- and
peritoneal dialysates do not represent sources of Cu. However, it is important that the plumbing
within the water pathway leading to the water preparation area for hemodialysate does not have any
copper piping. This is an especially important consideration when reviewing the home situations
for patients who will be hemodialyzed at home using their tap water to generate dialysate in a pro-
portioning dialysis system. This is of much less concern now because home HD machines that have
a premixed dialysis solution are available. Cu contamination of water supplies in devastated areas
would be unlikely to cause Cu overload and toxicity as long as the untreated water is used for only
23 dialysis sessions or a dialysis sorbent system is used.
3.2.3.2 Recommendations
It is highly unlikely that Cu deficiency will be seen in the United States. The clinical scenario in
which Cu deficiency is likely to be seen is severe malnutrition with little to no intake of food or
severe malabsorption. Milk-fed babies are at risk, as are patients with a previous gastrectomy or
gastric bypass surgery with a Roux-en-Y diversion, and patients on long-term oral Zn supplementa-
tion. Since Cu deficiency mimics vitamin B12 deficiency, it should be considered when vitamin B12
deficiency is suspected. At-risk populations also include the homeless, alcoholics and drug addicts,
and children or psychiatrically disturbed patients who swallow Zn-containing objects such as coins.
Serum Cu levels should be measured; however, the utility of ceruloplasmin concentrations in diag-
nosing Cu deficiency in patients with CKD is unknown. Cu can be administered by increasing the
patients dietary intake of Cu-containing foods or by the oral or parenteral use of TE solutions.
3.2.4 Fluoride
3.2.4.1 Metabolism
Fluoride (F) is a ubiquitous mineral in the earths crust, but its concentration in natural water sup-
plies is quite variable. It is known to be important in preventing dental caries and has been added
to the drinking water in most public water supplies in the United States for many years. It is a ben-
eficial TE rather than an essential TE (10th Edition of the RDAs, 1989a). Other important sources
46 Nutrition Therapy for Chronic Kidney Disease
of F are black tea, seafood with edible bones or shells (sardines, herring, soft-shell crabs), supple-
ments, and fluoridated toothpaste and mouthwash. Dietary F is rapidly absorbed in the stomach and
small intestines. Up to one-third of ingested F is deposited in calcified tissue; the rest is excreted by
the kidney (Stamp, 1993). Fluoride displaces hydroxyapatite and produces fluorapatite or fluorhy-
droxyapatite. Over 99% of the total body F is contained within bones. F supplementation causes an
increase in bone density, but there is no corresponding decrease in fractures; nonvertebral fractures
may actually increase (Haguenauer et al., 2000).
Other than an increase in dental caries, there is no known disease caused by F deficiency.
Fluoride toxicity is caused by ingestion of high amounts of F by water, use of F-containing medi-
caments (toothpaste, especially flavored toothpastes in children; F-containing mouthwash), F sup-
plements, exposure to fluorine-containing insecticides, or in industrial exposure, for example, to
hydrofluoric acid (HF) acid (Augenstein et al., 1991). Nonspecific GI complaints are the hallmark of
acute fluoride toxicity, which may lead to kidney and cardiac failure, coma, and death. Exposure to
small amounts of F in children (F-containing mouthwash or toothpaste ingestion) can cause acute F
toxicity (Augenstein et al., 1991).
Chronic toxicity is generally caused by high F concentrations in drinking water and the use of
F supplements or F-containing products such as mouthwash or pica for toothpaste in adults. Dental
fluorosis, a cosmetic disorder with mottled teeth is caused by high-F intake. In more severe instances,
there may be skeletal fluorosis, a condition in which radiologically, bone appears dense but is brittle
and prone to fracture, and ligaments can calcify, leading to joint immobility (Stamp, 1993). Other than
fluorosis, it is not evident that chronic F intoxication is seen more often in CKD patients compared to
normal patients. Acute fluoride poisoning occurs in industrial accidents and in intentional overdoses.
Acute dialysis may be effective in patients who receive medical attention (Bjornhagen et al., 2003).
Bottled water that is produced by a process of reverse osmosis and replenished with minerals is low in
F. Water used for the preparation of dialysate is treated by reverse osmosis, and the F content is well
within Association for Advancement of Medical Instrumentation (AAMI) standards (<0.02 mg/L). It
is unlikely that F toxicity would be seen in an adult CKD or ESRD population. The possibility of F
toxicity in the pediatric population is always present.
3.2.5 Chromium
3.2.5.1 Metabolism
Less than 3% of ingested chromium (Cr) is absorbed, and plasma levels are therefore quite low
(0.050.50 mcg/L) (Johnson, 2008a). Because Cr potentiates insulin activity, Cr deficiency has
been associated with glucose intolerance. Low plasma Cr levels have been described in patients
with glucose intolerance, diabetes mellitus, hypercholesterolemia, and in aged persons (Linder,
1991). Crdeficiency has also been described in patients receiving long-term TPN who exhibited
weight loss, ataxia, and peripheral neuropathy; most responded when trivalent Cr was administered
(Johnson, 2008a). Skin irritation occurs with high-dose trivalent Cr therapy, but lower doses are
well tolerated. Industrial exposure to hexavalent Cr (CrO3) is associated with lung and skin irrita-
tion, GI disturbances, nasal perforation, and lung cancer (Johnson, 2008a).
Dialyzed patients and renal transplant patients have increased whole-blood and serum Cr levels
(Danielson et al., 1986; Granadillo et al., 1994; Wallaeys et al., 1986). Chromium-rich dialysate may be
the source of the Cr since the Cr levels were increased in the dialyzed patients (Thomson et al., 1983).
There is no known Cr toxicity in CKD or ESRD patients unless they have significant industrial exposure.
3.2.6 Aluminum
3.2.6.1 Metabolism
Aluminum (Al) is the most ubiquitous and abundant metal. It is found in natural waters, plants,
animals, and the earths crust (Jiang et al., 2008; Verstraeten et al., 2008). Al is trivalent and highly
Electrolyte and AcidBase Disorders 47
reactive and is only found bound with other elements. The amount of Al in the diet is exceedingly
small and of no consequence unless there is renal impairment. Al is used in water purification
systems, which remove organic compounds that can bind free Al, thereby increasing the amount of
free Al in the water supply. Again, with normal renal function, this is of no consequence. Given the
usual water intake in humans of 14 + L/d depending upon the climate, Al intoxication from the
oral intake of treated municipal water does not occur. It is a totally different matter when a patient
is hemodialyzed where the patient may be exposed to 270720 L of water as dialysate per week.
Clearly, dialysis water supplies must be Al-free.
Al does not appear to be a required TE for normal physiological functioning. Because of its
atomic weight and electrical charge, it is a competitive inhibitor of several essential minerals (cal-
cium, magnesium, and iron). Over 95% of ingested Al is bound to transferrin and albumin in the
intravascular space. It is then eliminated through the kidneys. Al will only accumulate in the human
when there is increased oral or intravenous intake of Al in patients with AKI, CKD, or ESRD.
Association for Advancement of Medical Instrumentation (AAMI) (Brown et al., 2008; Mayor
etal., 1981).
Patients with an impaired GFR are at risk of Al intoxication if they are treated with Al salts
[Al(OH)3] used as phosphate-binding agents in CKD, intravenously through contaminated dialysate
or TPN, or through bladder irrigation with Al-containing solution. Lactate, citrate, and ascorbate
all increase Al absorption from the GI tract. These compounds should not be taken by patients who
are receiving oral aluminum products. The effects of Al cookware and Al-containing antiperspi-
rants on Al levels in patients with an impaired GFR are not known. Excess Al is deposited in bone,
brain, muscle, heart, liver, and spleen. Up to this time, no biological function has been attributed to
this metal. More importantly, Al accumulation in the tissues and organs results in dysfunction and
toxicity.
Acute Al intoxication is rare. The original reports described dialysis patients whose dialysate
was made with untreated water who developed an osteomalacic form of renal osteodystrophy. This
improved when the dialysate was prepared with deionized water (Ward et al., 1978). The dominant
feature of this bone disease was a defect in mineralization of bone and excessive deposits of alu-
minum at the osteoid mineralization front where calcium should have been deposited. A dialysis
encephalopathy was described that was thought to be due to Al deposition in the brain, and high Al
levels were noted in patients receiving dialysis with high Al-containing dialysate (Alfrey et al., 1976).
The elimination half-life of Al in the brain is 7 years, which can lead to cumulative damage.
Al has been suggested as an agent in the development of Alzheimers disease and possibly autism
spectrum disorders (Blaylock and Strunecka, 2009; Ferreira et al., 2008). Al acts as an excito-
toxin, which can exacerbate a clinical disorder by increasing cell excitation and oxidative stress and
by priming microglial cells to proliferate (Bihaqi Blaylock and Strunecka, 2009; Mailloux et al.,
2009). Excitotoxicity describes the process of neuron damage and death that is caused by overactive
receptors such as the N-methyl D-aspartate (NMDA) and -amino-3-hydroxy-5-methyl-4-isoxazole
propionic acid (AMPA) receptors for glutamate, an excitatory neurotransmitter. Excitotoxins bind
to these receptors and in the presence of high intracellular glutamate allow high levels of calcium
to enter the cell. This activates several enzymes that cause cell damage and death, including phos-
pholipases, proteases, and endonucleases (Science Daily, 2011). Brain Al can cause these changes
to occur (Blaylock, 2009). Al has a direct toxic effect on hematopoiesis and can cause a micro-
cytic anemia very similar to that found in patients suffering from lead intoxication. Al intoxication
results in decreased heme synthesis and may be related to increased hemolysis although the role
of PTH as a cause of decreased RBC survival in ESRD patients is unclear (Foulks et al., 1989;
Wu et al.,1998). Al also directly interferes with iron absorption and iron transport in addition to
competitively replacing iron binding to transferrin (Dreke et al., 1986). Anemia exacerbated by Al
overload was commonly seen into the 1980s when toxic Al-containing phosphate-binding agents
were gradually replaced by calcium-containing binding agents such as calcium carbonate, calcium
acetate, and calcium lactate.
48 Nutrition Therapy for Chronic Kidney Disease
Aluminum may cause anemia through decreased heme synthesis, decreased globulin synthesis,
and increased hemolysis. Aluminum may also have a direct effect on iron metabolism: it influences
absorption of iron via the intestine; it hinders irons transport in the serum; and it displaces irons
binding to transferrin. Patients with anemia from Al toxicity often have increased reticulocyte
counts, decreased mean corpuscular volume, and mean corpuscular hemoglobin (Bernardo et al.,
2010).
Considering the increasing prevalence of CKD in our society, it behooves us to review what is
known about Al absorption from the diet and from the use of Al cookware and packaging. The best
review is by Fimreite et al. (1997), who showed that cooking in an aluminum container, especially
if the food being cooked was acidic, caused a significant increase in the Al content of the food. This
was also seen in brewed tea. Significant Al accumulation has also been found in coffee brewed and
reheated in aluminum percolators (Lione et al., 1984). The content of Al in various liquids boiled
in an Al pot increased 10945-fold depending upon the liquid (the lowest was coffee; the highest,
2% acetic acid). The Al content of various beverages ranged from 53 mcg/L for apple juice in an
aluminum-foil-lined carton to 1800 mcg/L in tea with lemon. Coca-Cola had an Al concentration
of 70 mcg/L (Nagy and Jobst, 1994). Clearly, dietary Al sources can present a large amount of Al
to the GI tract. This poses no problem to those with normal kidney function but could be of con-
sequence to those with advanced CKD who live for a long time. When CKD patients were studied
while using aluminum kitchen utensils compared to the use of stainless steel kitchen utensils, serum
aluminum levels and urinary excretion of aluminum were significantly higher among the patients
using aluminum utensils. This suggests that patients with CKD should be concerned about the long-
term use of aluminum cooking utensils (Lin et al., 1997).
3.2.6.2 Recommendations
At this time, Al-containing phosphate-binding agents should not be used for the chronic long-
term management of hyperphosphatemia and secondary hyperparathyroidism. Many safer
agents, such as calcium carbonate, calcium acetate, sevelamer, lanthanum, and others, are avail-
able. Rarely, Al(OH)3 may be used as a phosphate-binding agent for a period not to exceed
a week. This may come into play when the CKD or ESRD patient has extremely high phos-
phate levels (>15) and/or a very elevated CaXP product (>100). Al-salts should never be used in
patients who are receiving citrate. Patients who have CKD and are presumed to have longevity
should probably be cautioned about extensive use of Al-containing cookware and of large intake
of beverages in Al-containing cans.
3.3 CONCLUSION
TE roles and disorders in CKD and ESRD patients are still poorly understood. Many of the method-
ological publications appeared at a time when dialysis adequacy was poorly understood and medical
technologies were less advanced than they are today. We still have insufficient information about
many TEs. The metabolism of even those TE that are known to be necessary such as Mo has not
been fully explored in non-CKD patients, let alone in CKD and ESRD patients. Zn supplementa-
tion may be of use in clinical circumstances, but one should be careful about giving Zn to potential
renal transplant patients because of the risk of stimulating a rejection episode, although the degree
of this risk during our modern era of excellent antirejection drugs is unknown. Cu deficiency does
occur but is rare, as is Cr deficiency. Se deficiency is likely unusual as well. Common to TE dis-
orders are malnutrition, malabsorption syndromes, severe or chronic diarrhea, impaired GI trans-
port, increased need due to illness, and genetic disorders. The clinical presentations of many of
these deficiencies are very similar to the uremic state and to common complaints seen in CKD and
ESRD patients, and it is difficult to separate them. As in most clinical situations, the wise clinician
observes, correlates, and keeps an open mind.
Electrolyte and AcidBase Disorders 49
REFERENCES
Alfrey, A., LeGendre, G., Kaehny, W. 1976. The dialysis encephalopathy syndrome. Possible aluminum intoxi-
cation. N Engl J Med. 294(4):184188.
American Dietetic Association, Dietitians of Canada. 2003. Position of the American Dietetic Association and
Dietitians of Canada: Vegetarian diets. J Am Diet Assoc. 103:748765.
Antoniou, L. and Shalhoub, R. 1985. Zinc-induced enhancement of lymphocyte function and viability in
chronic uremia. Nephron 40:1421.
Antoniou, L., Sudhakar, T., Shalhoub, R., et al. 1997. Reversal of uraemic impotence by zinc. Lancet
350:895898.
Augenstein, W., Spoerke, D., Kulig, K., et al. 1991. Fluoride ingestion in children: A review of 87 cases.
Pediatrics 88(5):907912.
Bernardo, J., Edwards, M., Barnett, B. 2010. Toxicity, Aluminum. http://emedicine.medscape.com/
article/165315-overview
Bihaqi, S., Sharma, M., Singh, A., et al. 2009. Neuroprotective role of Convolvulus pluricaulis on aluminum
induced neurotoxicity in rat brain. J Ethnopharmacol. 124(3):409415.
Bjornhagen, V., Hojer, J., Karlson-Stiber, C., et al. 2003. Hydrofluoric acid-induced burns and life-threatening
systemic poisoning-favorable outcome after hemodialysis. J Toxicol Clin Toxicol. 41(6):855860.
Blaylock, R. 2009. A possible central mechanism in autism spectrum disorders, Part 3: The role of excito-
toxin food additives and the synergistic effects of other environmental toxins. Altern Ther Health Med.
15(2):5660.
Blaylock, R. and Strunecka, A. 2009. Immune-glutamatergic dysfunction as a central mechanism of the autism
spectrum disorders. Curr Med Chem. 16(2):157170.
Boaz, M. and Smetana, S. 1996. Regression equation predicts dietary phosphorus intake from estimate of
dietary protein intake. J Am Diet Assoc. 96:12681270.
Bonomini, M., Forster, S., De Risio, F., et al. 1995. Effects of selenium supplementation on immune parameters
in chronic uraemic patients on haemodialysis. Nephrol Dial Transplant. 10:16541661.
Borner, H., Mehnert, E., Falkenhagen, D., et al. 1984. Behavior of copper and manganese in serum in hemodi-
alysis. Urol Nephrol. 77:483487.
Briggs, W., Pedersen, M., Mahajan, S., et al. 1982. Lymphocyte and -granulocyte function in zinc-treated and
zinc-deficient hemodialysis patients. Kidney Int. 21:827832.
Brodersen, H., Holtkamp, W., Larbig, D. 1994. Zinc supplementation and cellular and humoral immune func-
tion in chronic haemodialysis patients. Nephrol Dial Transplant. 9:736737.
Brown, R., Morgan, L., Bhattacharya, S., et al. 2008. Potential aluminum exposure from parenteral nutrition in
patients with acute kidney injury. Ann Pharmacother. 42(10):14101415.
Burk, R.F, and O.A. Levander. 1999. Selenium. In M. Shils, J. Olson, M. Shike, and A. C. Ross, eds., Modern
Nutrition in Health and Disease, 9th Edition. Baltimore, MD: Williams & Wilkins, 265276.
Calton, J. 2010. Prevalence of micronutrient deficiency in popular diet plans. J Int Soc Sports Nutr. 7:24. http://
www.ncbi.nlm.nih.gov/pubmed/20537171
Caulfield, L., Zavaleta, N., Shankar, A., et al. 1998. Potential contribution of maternal zinc supplementation
during pregnancy to maternal and child survival. Am J Clin Nutr. 68(2 Suppl):499S508S.
Chan, W. and Rennert, O. 1980. The role of copper in iron metabolism. Ann Clin Lab Sci. 10:338344.
Charlton, K., Steyn, K., Levitt, N., et al. 2007. Development and validation of a short questionnaire to assess
sodium intake. Public Health Nutr. 11(1):8394.
Cousins, R. 1996. Zinc. In Zioegler, E. and Filer, I., eds. Present Knowledge in Nutrition, 7th ed. Washington:
ILSI Press, 293306.
Dai, L., Ritchio, G., Kerstan, D., et al. 2001. Magnesium transport in the renal distal convoluted tubule. Physiol
Rev. 81:5184.
Danielson, B., Fellstrom, B., Nilsson, P., et al. 1986. Trace element levels in patients with renal failure and after
transplantation. Acta Pharmacol Toxicol. 59:438441.
Danks, D. 1988. Copper deficiency in humans. Annu Rev Nutr. 8:235257.
Dawson-Hughes, B. 2003. Calcium and protein in bone health. P. Nutr. Soc. 62:505509.
Dreke, T., Lacour, B., Touam, M., et al. 1986. Effect of aluminum on hematopoiesis. Kidney Int Suppl.
18:S45S48.
Eggert, J., Siegler, R., Edomkesmalee, I. 1982. Zinc supplementation in chronic renal failure. Int J Pediatr
Nephrol. 3:2124.
Fabris, N. and Mocchegiani, E. 1995. Zinc, human diseases and aging. Aging (Milano) 7:7793.
Fawcett, W., Haxby, E., Male, D. 1999. Magnesium: Physiology and pharmacology. Br J Anaesth. 83:302320.
50 Nutrition Therapy for Chronic Kidney Disease
Ferreira, P., Piaikde, A., Takayangui, A., et al. 2008. Aluminum as a risk factor for Alzheimers disease. Rev Lat
Am Enfermagem. 16(1):151157.
Fimreite, N., Hansen, O., Pettersen, H. 1997. Aluminum concentrations in selected foods prepared in aluminum
cookware, and its implications for human health. Bull Environ Contam Toxicol. 58(1):17.
Fleming, C. 1989. Trace element metabolism in adult patients requiring total parenteral nutrition. Am J Clin
Nutr. 49:573579.
Foulks, C., Mills, G., Wright, L. 1989. Parathyroid hormone and anaemiaAn erythrocyte osmotic fragility
study in primary and secondary hyperparathyroidism. Postgrad Med J. 65:136139.
Fox, C., Gona, P., Larson, M., et al. 2010. A multi-marker approach to predict incident CKD and microalbu-
minuria. J Am Soc Nephrol. 21:21432149.
Fox, C., Ramsoomair, D., Carte, C. 2002. Magnesium: Its proven and potential clinical significance.
SouthMedJ. 94:11951201. medscape.com/viewarticle/423568_print
Girelli, D., Olivieri, O., Stanzial, A., et al. 1993. Low platelet glutathione peroxidase activity and serum sele-
nium concentration, in patients with chronic renal failure: Relations to dialysis treatments, diet and car-
diovascular complications. Clin Sci. 84:611617.
Granadillo, V., Parra de Machado, L., Romero, R. 1994. Determination of total chromium in whole blood,
blood components, bone, and urine by fast furnace program electrothermal atomization AAS and using
neither analyte isoformation nor background correction. Anal Chem. 66:36243631.
Grekas, D., Alivanis, P., Kotzadamis, N., et al. 1992. Influenza vaccination in chronic hemodialysis patients.
The effect of zinc supplementation. Ren Fail. 14:575578.
Grekas, D., Tsakalos, N., Giannopoulus, Z., et al. 1985. Effect of zinc treatment on cell mediated immunity of
chronic renal failure patients. Proc Eur Dial Transplant Assoc Eur Ren Assoc. 21:825829.
Griffith, D., Liff, D., Ziegler, T., et al. 2009. Acquired copper deficiency: A potentially serious and preventable
complication following gastric bypass surgery. Obesity (Silver Spring). 17(4):827831.
Haguenauer, D., Welch, V., Shea, B., et al. 2000. Fluoride for the treatment of postmenopausal osteoporotic
fractures: A meta-analysis. Osteoporos Int. 11(9):727738.
Hambidge, K. 1989. Mild zinc deficiency in human subjects. In Mills, C.F., ed. Zinc in Human Biology. New
York: Springer-Verlag, 281296.
Harris, E. 2000. Cellular copper transport and metabolism. Annu Rev Nutr. 20:291310.
Harris, E.D. 1995. The iron-copper connection: The link to ceruloplasmin grows stronger. Nutr Rev.
53:170173.
Harvard Medical School. 2010. Salt and your health series. The Sodium Connection. Har Mens Health Watch
15:34.
Hasanolu, E., Altan, N., Sindel, S., et al. 1994. The relationship between erythrocyte superoxide dismutase
activity and plasma levels of some trace elements (Al, Cu, Zn) of dialysis patients. Gen Pharmacol.
25:107110.
Hawkes, W. and Hornbostel, L. 1996. Effects of dietary selenium on mood in healthy men living in a metabolic
research unit. Biol Psychiatry. 39:121128.
Heyneman, C. 1996. Zinc deficiency and taste disorders. Ann Pharmacother. 30:186187.
Holtkamp, W., Brodersen, H., Thiery, J., et al. 1991. Effect of zinc substitution on lymphocyte subsets and cel-
lular immune function in hemodialysis. Lkin Wochenschr. 69:392396.
Hosokawa, S., Nishitani, H., Tomita, K., et al. 1985. Serum copper concentration changes in chronic hemodi-
alysis patients. Uremia Invest. 9:6367.
Hosokawa, S., Nishitani, H., Umemura, K., et al. 1990a. Serum and corpuscular nickel and zinc in chronic
hemodialysis patients. Nephron. 45:151153.
Hosokawa, S., Oyamaguchi, A., Yoshida, O. 1990b. Trace elements and complications in patients undergoing
chronic hemodialysis. Nephron. 55:375379.
Hosokawa, S. and Yoshida, O. 1993. Effects of erythropoietin on trace elements in patients with chronic renal
failure undergoing hemodialysis. Nephron. 65:414417.
Hosokawa, S. and Yoshida, O. 1995. Effects of recombinant human erythropoietin (rHuEPO) on protein
zinc (Zn), nickel (Ni) and manganese (Mn) in patients undergoing hemodialysis. Int Urol Nephrol.
27:207214.
Hunt, J. 2003. Bioavailability of iron, zinc, and other trace minerals from vegetarian diets. Am J Clin Nutr. 78
(3 Suppl):633S639S.
Ikizler, T. 2009. CKD classification: Time to move beyond KDOQI. J Am Soc Nephrol. 20:929930.
Institute of Medicine, Food and Nutrition Board. 2001. Dietary Reference Intakes for Vitamin A, Vitamin K,
Arsenic, Boron, Chromium, Copper, Iodine, Iron, Manganese, Molybdenum, Nickel, Silicon, Vanadium,
and Zinc. Washington, DC: National Academy Press.
Electrolyte and AcidBase Disorders 51
Isakova, T. and Wolf, M. 2010. FGF23 or PTH: Which comes first in CKD? Kidney Int. 78:947949.
Ix, J., De Boer, I., Peralta, C., et al. 2009. Serum phosphorus concentrations and arterial stiffness among
individuals with normal kidney function to moderate kidney disease in MESA. Clin J Am Soc Nephrol.
4:609615.
Jiang, H., Chen, L., Zheng, J., et al. 2008. Aluminum-induced effects on Photosystem II photochemistry in
citrus leaves assessed by the chlorophyll a fluorescence transient. Tree Physiol. 28(12):18631871.
Johnson, L. 2008a. Chromium. In The Merck Manuals Online Medical Library. www.merckmanuals.com.
Johnson, L. 2008b. Copper. In The Merck Manuals Online Medical Library. www.merckmanuals.com.
Johnson, L. 2008c. Molybdenum. In The Merck Manuals Online Medical Library. www.merckmanuals.com.
Johnson, L. 2008d. Selenium. In The Merck Manuals Online Medical Library. www.merckmanuals.com.
Johnson, M. and Kays, D. 1990. Copper: Its role in human nutrition. Nutr Today. 25:6.
Joven, J., Villabona, C., Rubies-Prat, J., et al. 1985. Hormonal profile and serum zinc levels in uraemic men
with gonadal dysfunction undergoing hemodialysis. Clin Chem Acta. 148:239245.
Juhasz-Pocsine, K., Rudnicki, S., Archer, R., et al. 2007. Neurologic complications of gastric bypass surgery
for obesity. Neurology. 68:18431850.
Kalantar-Zadeh, K., Gutekunst, L., Mehrotra, R., et al. 2010. Understanding sources of dietary phosphorus in
the treatment of patients with chronic kidney disease. Clin J Am Soc Nephrol. 5:519530.
King, J. and Cousins, R. 2005. Zinc. In Shils, M., Shike, M., Ross, A., et al., eds. Modern Nutrition in Health
and Disease, 10th ed. Baltimore, MD: Lippincott Williams & Wilkins, 271285.
Koenig, J., Fischer, M., Bulant, E., et al. 1997. Antioxidant status in patients on chronic hemodialysis therapy:
Impact of parenteral selenium supplementation. Wein Klin Wochenschr. 109:1319.
Kouw, P., Konings, C., deVries, P.M, et al. 1991. Effects of zinc supplementation on zinc status and immunity
in haemodialysis patients. J Trace Elem Electrolytes Health Dis. 5:115119.
Krebs, F. 1998. Zinc supplementation during lactation. Am J Clin Nutr 68 (2 Suppl):509S512S.
Kumar, N., Ahlskog, J., Gross, J. 2004. Acquired hypocupremia after gastric surgery. Clin Gastroenteroal
Hepatol. 2:10741079.
Lewis, J. 2009. Disorders of magnesium metabolism. In The Merck Manuals Online Medical Library. http://
www.merckmanuals.com/professional/sec12/ch156/ch156i.html#sec12-ch156-ch156i-956.
Lin, T., Chen, J., Liaw, J., et al. 1996. Free elements and lipid peroxidation in uremic patients on hemodialysis.
Biol Trace Elem Res. 51:277283.
Lin, J.L., Yang, Y.J., Yang, S.S., and Leu, M.L. November 1997. Aluminum utensils contribute to aluminum
accumulation in patients with renal disease. Am J Kidney Dis., 30(5):653658.
Linder, M. 1991. Nutrition and metabolism of the trace elements. In Linder, M., ed. Nutritional Biochemistry
and Metabolism with Clinical Application, 2nd ed. Englewood Cliffs: Prentice-Hall, 215276.
Linder, M. 1996. Nutrition and metabolism of the trace elements. In Ziegler, E. and Filer, L., eds. Present
Knowledge in Nutrition. Washington, DC: ISLI Press, 215276.
Lione, A., Allen, P., Smith, J. 1984. Aluminum coffee percolators as a source of dietary aluminum. Food Chem
Toxicol. 22(4):265268.
Lutsenko, S. April 2010. Human copper homeostasis: a network of interconnected pathways. Curr Opin Chem
Biol., 14(2):211217. Epub February 1, 2010.
Mahajan, S., Abbasi, A., Prasad, A., et al. 1982a. Effect of oral zinc therapy on gonadal function in hemodialy-
sis patients. A double-blind study. Ann Intern Med. 97:357361.
Mahajan, S., Bowersox, E., Rye, D., et al. 1989. Factors underlying abnormal zinc metabolism in uremia.
Kidney Int. 36(suppl 27):269273.
Mahajan, S., Prasad, A., Rabbani, P., et al. 1982b. Zinc deficiency: A reversible complication of uremia. Am J
Clin Nutr. 36:11771183.
Maher, E., Sampson, B., Curtis, J. 1987. Is selenium deficiency the cause of uraemic cardiomyopathy? Adv Exp
Med Biol. 223:221230.
Mailloux, R., Puiseux-Dao, S., Appanna, V. 2009. Alpha-ketoglutarate abrogates the nuclear localization of
HIF-1alpha in aluminum-exposed hepatocytes. Biochimie. 91(3):408415.
Maret, W. and Sandstead H. 2006. Zinc requirements and the risks and benefits of zinc supplementation.
JTrace Elem Med Biol. 20:318.
Mayor, G., Sprague, S., Sanchez, T. 1981. Determinants of tissue aluminum concentration. Am J Kidney Dis.
1(3):141145.
Menzano, E. and Carlen, P. 1994. Zinc deficiency and corticosteroids in the pathogenesis of alcoholic brain
dysfunctionA review. Alcohol Clin Exp Res. 18:895901.
Migneco, C., Tripi, S., Navett, A., et al. 1990. Serum zinc concentration and antibody response to hepatitis B
vaccine. Minerva Med. 81:1921.
52 Nutrition Therapy for Chronic Kidney Disease
Muirhead, N., Kertesz, A., Flanagan, P., et al. 1986. Zinc metabolism in patients on maintenance hemodialysis.
Am J Nephrol. 6:422426.
Nagy, E. and Jobst, K. 1994. Aluminum dissolved from kitchen utensils. Bull Environ Contam Toxicol.
52:396399.
Naito, S., Ohta, A., Sohara, E., et al. 2010. Regulation of WNK1 kinase by extracellular potassium. Clin Exper
Nephrol. 12 September, 195202. DOI 10.1007/s10157-010-0378-9
Napolitano, G., Bonomini, M., Bomba, G., et al. 1996. Thyroid function and plasma selenium in chronic ure-
mic patients on hemodialysis treatment. Biol Trace Elem Res. 55:221230.
National Kidney Foundation. 2003. K/DOQI clinical practice guidelines for bone metabolism and disease in
chronic kidney disease. Am J Kidney Dis. 42(Suppl 3):S1S201.
Navarro, S., Valderrama, R., To-Figueras, J., et al. 1994. Role of zinc in the process of pancreatic fibrosis in
chronic alcoholic pancreatitis. Pancreas. 9:270274.
Office of Dietary Supplements. 2009. NIH, Dietary Supplement Fact Sheet: Zinc. http://ods.od.nih.gov/
FactSheets/Zinc/.
Peacock, M. 2010. Calcium metabolism in health and disease. Clin J Am Soc Nephrol. 5:S23S30.
Picchota, W., Dobrucki, T., Symonowicz, N., et al. 1983. Zinc in patients with chronic renal failure. Int Urol
Nephrol. 15:377382.
Prasad, A. and McDonald, F. 1982. Lymphocyte and granulocyte function in zinc-treated and zinc-deficient
hemodialysis patients. Kidney Int. 21:827832.
Prasad, A. 1985. Clinical, endocrinological and biochemical effects of zinc deficiency. Clin Endocrinol Metab.
14:567.
Prasad, A. 1995. Zinc: An overview. Nutrition 11:9399.
Prasad, A. 1996. Zinc deficiency in women, infants and children. J Am Coll Nutr. 15:113120.
Prasad, A., Beck, F., Grabowski, S., et al. 1997. Zinc deficiency: Changes in cytokine production and T-cell sub-
populations in patients with head and neck cancer and in noncancer subjects. Proc Assoc Am Physicians.
109:6877.
Quamme, G.A. 1997. Renal magnesium handling: New insights in understanding old problems. Kidney Int.,
52(5):11801195.
Rastergar, A. and Soleimani, M. 2001. Hypokalaemia and hyperkalaemia. Postgrad Med J. 77:759764.
Rayman, M.2000. The importance of selenium to human health. Lancet. 356:233241.
Richard, M., Arnaud, J., Jurkovits, C., et al. 1991. Trace elements and lipid peroxidation abnormalities in
patients with chronic renal failure. Nephrol 57:1015.
Rodger, R., Sheldon, W., Watson, M., et al. 1989. Zinc deficiency and hyperprolactinemia are not reversible
causes of sexual dysfunction in uraemia. Nephrol Dial Transplant. 4:888892.
Rude, R. 1993. Magnesium metabolism and deficiency. Endocrinol Clin North Am. 22:377390.
Saint-Georges, M., Bonnefont, D., Bourely, B., et al. 1989. Correction of selenium deficiency in hemodialyzed
patient. Kidney Int. 27(suppl):274277.
Sandstrom, B. 1997. Bioavailability of zinc. Eur J Clin Nutr. 51(1 Suppl):S17S19.
Science Daily. 2011. Excitotoxicity and cell damage. http://www.sciencedaily.com/articles/e/excitotoxicity.
htm
Shaw, J. 1992. Copper deficiency in term and preterm infants. In Fomon, S. and Zlotkin, S., eds. Nutritional
Anemias. New York: Vevey/Raven Press, 105.
Saris, N., Mervaala, E., Karppanen, H., et al. 2000. Magnesium. An update on physiological, clinical, and ana-
lytical aspects. Clin Chim Acta. 291:146.
Simmer, K. and Thompson, R. 1985. Zinc in the fetus and newborn. Acta Paediatr Scand Suppl. 319:158163.
Solomons, N. 1998. Mild human zinc deficiency produces an imbalance between cell-mediated and humoral
immunity. Nutr Rev. 56:2728.
Sondheimer, J., Mahaman, S., Rye, D., et al. 1988. Elevated plasma copper in chronic renal failure. Am J Clin
Nutr. 47:896899.
Stec, J., Podracha, L., Pavkovcekova, O. 1990. Zinc and copper metabolism in nephritic syndrome. Nephron
56(2):186187.
Subcommittee on the Tenth Edition of the RDAs. 1989a. Fluoride. In Recommended Dietary Allowances, 10th
ed. Washington, DC: National Academy Press.
Subcommittee on the Tenth Edition of the RDAs. 1989b. Selenium. In Recommended Dietary Allowances, 10th
ed. Washington, DC: National Academy Press.
Swaminathan, R. 2003. Magnesium metabolism and its disorders. Clin Biochem Rev. 24(2):4766.
Tan, J., Burns, D., Jones, H. 2006. Severe ataxia, myelopathy, and peripheral neuropathy due to acquired copper
deficiency in a patient with a history of gastrectomy. J Parenter Enteral Nutr. 30:446450.
Electrolyte and AcidBase Disorders 53
Tang, X., Santarelli, L., Heinemann, S., et al. 2004. Metabolic regulation of potassium channels. Annu Rev
Physiol. 66:131159.
Taylor, E. and Curhan, G. 2009. Demographic, dietary, and urinary factors and 24-h urinary calcium excretion.
Clin J Am Soc Nephrol. 4:19801987.
Thomas, C. and Robinson, M. 1993. Selenium. In Macrae, R., Robinson, R., Sadler, M., eds. Encyclopedia of
Food Science, Food Technology, and Nutrition. London: Academic Press, 51175124.
Thomson, N., Stevens, B., Humphrey, T. 1983. Comparison of trace elements in peritoneal dialysis, hemodi-
alysis and uremia. Kidney Int. 23:914.
Tonelli, M., Wiebe, N., Hemmelgarn, B., et al. 2009. Trace elements in hemodialysis patients: A systematic
review and meta-analysis. BMC Med. 7:25, online publication.
Tzanakis, I., Papadaki, A., Mingxin, W., et al. 2008. Magnesium carbonate for phosphate control in patients on
hemodialysis. A randomized controlled trial. Int Urol Nephrol. 40(1):193201.
Unwin, R., Luft, F., Shirley, D. 2011. Pathophysiology and management of hypokalemia: A clinical perspec-
tive. Nature Rev Nephrol. 7:7584.
Valberg, L., Flanagan, P., Kertesz, A., et al. 1986. Zinc absorption in inflammatory bowel disease. Dig Dis Sci.
31(7):724731.
Van Renterghem, D., Cornelis, R., Mees, L., et al. 1992. The effect of adding Br or Zn supplements to the dialy-
sate on the concentrations of Br and zinc in the blood of hemodialysis patients. J Trace Elem Electrolytes
Health Dis. 6:105109.
Verstraeten, S., Aimo, L., Oteiza, P. 2008. Aluminum and lead: Molecular mechanisms of brain toxicity. Arch
Toxicol. 82(11):789802.
Wallaeys, B., Cornelia, R., Mees, L., et al. 1986. Trace elements in serum, packed cells, and dialysate of CAPD
patients. Kidney Int. 30:599604.
Wang, W., Hebert, S., Giebisch, G., 1997. Renal K+ Channels: Structure and function. Annu Rev Physiol.
59:413436.
Ward, M., Feest, T., Ellis, H., et al. 1978. Osteomalacic dialysis osteodystrophy: Evidence for a water-borne
aetiological agent, probably aluminum. Lancet. 1(8069):841845.
Watson, A., Stuart, A., Wells, F., et al. 1983. Zinc supplementation and its effect on taste acuity in children with
chronic renal failure. Hum Nutr Clin Nutr. 37:219225.
Weir, M. and Rolfe, M. 2010. Potassium homeostasis and renin-angiotensin-aldosterone system inhibitors. Clin
J Am Soc Nephrol. 5:531548.
Whang, R., Hampton, E.M., Whang, D.E.D. 1994. Magnesium homeostasis and clinical disorders of magne-
sium deficiency. Ann Pharmacother.28:220225.
Wise, A. 1995. Phytate and zinc bioavailability. Int J Food Sci Nutr. 46:5363.
Wu, S., Jeng, F., Wie, S. 1998. Red blood cell osmotic fragility in chronically hemodialyzed patients. Nephron
78:2832.
4 Acute Kidney Injury
Pranay Kathuria and Anand Khurana
University of Oklahoma-Tulsa
CONTENTS
4.1 Definition................................................................................................................................. 56
4.2 Epidemiology........................................................................................................................... 56
4.3 Causes of AKI......................................................................................................................... 57
4.3.1 Prerenal Azotemia....................................................................................................... 57
4.3.2 Postrenal Causes.......................................................................................................... 57
4.3.3 Intrinsic AKI............................................................................................................... 58
4.3.3.1 Acute Tubular Necrosis................................................................................. 58
4.3.3.2 Acute Interstitial Nephritis...........................................................................60
4.3.3.3 Glomerulonephritis.......................................................................................60
4.3.3.4 Vascular Diseases.........................................................................................60
4.3.3.5 Crystal Nephropathies.................................................................................. 61
4.4 Evaluation of a Patient with AKI............................................................................................. 61
4.5 Management of AKI................................................................................................................ 62
4.5.1 Prerenal AKI and ATN............................................................................................... 62
4.5.1.1 Restoration of Effective Circulatory Volume............................................... 62
4.5.1.2 Identifying and Discontinuing Nephrotoxins............................................... 63
4.6 Postrenal AKI.......................................................................................................................... 63
4.6.1 Intrinsic AKI............................................................................................................... 63
4.7 General Supportive Therapy.................................................................................................... 63
4.8 Renal Replacement Therapies.................................................................................................64
4.9 Metabolic Changes in AKI......................................................................................................64
4.10 Energy Metabolism and Energy Requirements....................................................................... 65
4.10.1 Carbohydrate Metabolism........................................................................................... 65
4.10.2 Lipid Metabolism......................................................................................................... 65
4.10.3 Protein and Amino Acid Metabolism..........................................................................66
4.10.4 Metabolism and Requirements of Micronutrients.......................................................66
4.10.5 Electrolytes.................................................................................................................. 67
4.10.5.1 Potassium...................................................................................................... 67
4.10.5.2 Phosphorus.................................................................................................... 67
4.10.5.3 Calcium......................................................................................................... 67
4.10.5.4 Magnesium.................................................................................................... 67
4.10.6 Vitamins...................................................................................................................... 67
4.11 Assessment of Nutritional Status............................................................................................. 68
4.11.1 Patient Classification.................................................................................................... 69
4.12 Nutritional Support.................................................................................................................. 69
4.12.1 Enteral Feeding............................................................................................................ 69
4.12.2 Parenteral Nutrition..................................................................................................... 70
4.12.3 Renal Replacement Therapy........................................................................................ 71
References......................................................................................................................................... 71
55
56 Nutrition Therapy for Chronic Kidney Disease
4.1 DEFINITION
Acute renal failure (ARF) is an abrupt decrease in the glomerular filtration rate (GFR) occurring
over a period of hours to days, resulting in the failure of the kidney to excrete nitrogenous waste
products and maintain fluid and electrolyte homeostasis. The retention of nitrogenous wastes is
usually assessed by measuring blood urea nitrogen (BUN) and serum creatinine. However, imme-
diately after a kidney injury, BUN or creatinine levels may be normal, and the only sign of a kidney
injury may be decreased urine production.
The above definition is largely subjective, given that neither time nor the quantitative changes
in kidney function are specified. In past medical literature, more than 35 different definitions of
ARF have been used. This hampered our ability to characterize the true incidence of the disease,
assess its impact, and make progress in clinical and scientific research. All these factors led to the
realization that there needed to be a consensus definition of ARF. The term ARF was replaced by
acute kidney injury (AKI). AKI encompasses the entire spectrum of the syndrome from minor
changes in renal function to need for kidney replacement therapy. The initial definition of AKI was
proposed by the Acute Dialysis Quality Initiative (ADQI) and subsequently modified by the Acute
Kidney Injury Network (AKIN; Bellomo et al., 2004; Srisawat et al., 2010). AKI is defined as an
abrupt (within 48 h) reduction in kidney function with an absolute increase in serum creatinine of
more than or equal to 0.3 mg/dL, a percentage increase in serum creatinine of more than or equal
to 50% (1.5-fold from baseline), or a reduction in urine output (documented oliguria of less than 0.5
mL/kg/h for more than 6 h; Srisawat et al., 2010). The stages of AKI are summarized in Table 4.1.
4.2 EPIDEMIOLOGY
The worldwide incidence of AKI is poorly known because of underreporting, regional dispari-
ties, and differences in definition and case mix. It is recognized that the epidemiology of AKI in
developing countries differs from that of the developed world in many important ways. Whereas
in developed regions elderly patients predominate, in developing countries, AKI is a disease of
the young and children. In developing countries, the most common causes of AKI are frequently
associated with volume-responsive prerenal, obstetric, infectious or toxic mechanisms. In the
developed world, AKI is seldom a community-acquired disease; the condition develops primarily in
hospitalized patients. The common causes include sepsis, intravenous iodinated contrast and other
nephrotoxins, postoperative and hypovolemia. In these regions, the incidence of hospital-acquired
AKI exceeds that of community-acquired AKI by 510 times, having an estimated yearly incidence
of 0.15%7.2%. The incidence of AKI exceeds 20% in the critically ill patients (Cerda etal., 2008).
Approximately 4%5% of general intensive care unit patients will be treated with renal replacement
therapy (RRT). Intensive care unit patients with AKI have a longer length of stay and therefore
associated with greater costs. Patients with AKI have increased mortality, even after correction for
TABLE 4.1
Stages of Acute Kidney Injury (AKIN Classification)
AKI Stage Creatinine Criteria Urine Output Criteria
Stage I Increase of serum creatinine by 0.3 mg/dL or Urine output < 0.5 mL/kg/h for >6 h
increase to 150%200% from baseline
Stage II Increase of serum creatinine to >200%300% from Urine output < 0.5 mL/kg/h for >12 h
baseline
Stage III Increase of serum creatinine to >300% from baseline Urine output < 0.3 mL/kg/h for >24 h or
or serum creatinine 4.0 mg/dL with an acute rise an-uria for 12 h
of at least 0.5 mg/dL or treatment with RRT
Acute Kidney Injury 57
covariates. Patients treated with RRT have a mortality rate of 50%60%. Of surviving patients,
5%20% remain dialysis dependent at hospital discharge (Hoste and Schurgers, 2008).
TABLE 4.2
Causes of Prerenal Azotemia
1. Intravascular Volume Depletion
Acute blood loss
Gastrointestinal fluid loss (vomiting, diarrhea, NG suction)
Kidney losses (diuretics, hypoaldosteronism, diabetes inspidus)
Dermatological losses (burns, hyperthermia)
Third-space fluid loss (pancreatitis, peritonitis, crush syndrome)
2. Decreased Effective Circulating Volume
Reduced cardiac output (congestive heart failure, valvular diseases, pericardial tamponade,
pulmonary embolism, positive pressure ventilation)
Systemic vasodilatation (sepsis, anaphylaxis, cirrhosis, anesthetics)
Abdominal compartment syndrome
3. Intrarenal Hemodynamic Changes
Hepatorenal syndrome
Drugs: angiotensin-converting enzyme inhibitors, angiotensin receptor blockers,
cyclosporine, radiocontrast media, nonsteroidal anti-inflammatory drugs
Hypercalcemia
TABLE 4.3
Causes of Postrenal Acute Kidney Injury
1. Ureteral Obstruction
Intraureteral: Obstruction: Stones, blood clots, cancer, sloughed papillae
Extraureteral: Malignancy, retroperitoneal fibrosis, trauma or accidental ligation of ureter,
abdominal compartment syndrome
2.Bladder Neck: Neurogenic bladder, prostatic hyperplasia, calculi, blood clots, anticholinergic
drugs, malignancies of bladder, prostate or cervix
3. Urethral: Urethral strictures, posterior urethral valves, phimosis
is an easy way to make a diagnosis of a bladder or urethral obstruction. A kidney ultrasound will
detect obstructive uropathy with a very high sensitivity and specificity. False-negative ultrasound
examinations can occur if the obstruction is very early or retroperitoneal fibrosis is present.
TABLE 4.4
Intrinsic Acute Kidney Injury
1. Tubular
Ischemic
Nephrotoxic
Pigment (rhabdomyolysis, intravascular hemolysis)
Toxins (aminoglycosides, lithium, amphotericin B, pentamidine, cisplatinum, ifosfamide, radiocontrast agents)
2. Interstitial
Allergic (penicillins, cephalosporins, quinolones, sulfonamides, nonsteroidal anti-inflammatory drugs, allopurinol,
rifampin, mesalamine)
Infection (pyelonephritis, viral nephritides)
Systemic disease (Sjgren syndrome, sarcoidosis, lupus, lymphoma, leukemia, tubulonephritis with uveitis)
3. Glomerular
Antiglomerular basement membrane disease (Goodpasture syndrome)
Antineutrophil cytoplasmic antibody-associated glomerulonephritis (Wegener granulomatosis, ChurgStrauss
syndrome, microscopic polyangiitis)
Immune complex glomerulonephritis (GN) (lupus, postinfectious, cryoglobulinemia, primary
membranoproliferative glomerulonephritis)
4. Vascular (large and small vessel)
Renal artery obstruction (thrombosis, emboli, dissection, vasculitis)
Renal vein obstruction (thrombosis)
Microangiopathy (thrombotic thrombocytopenic purpura, hemolytic uremic syndrome, disseminated intravascular
coagulation, malignant hypertension, scleroderma renal crisis)
Atheroembolic disease
5. Crystal Nephropathies
Endogenous (uric acid, light chains, oxalosis)
Exogenous (phosphate, methotrexate, calcium oxalate, acyclovir, indinavir)
hemolysis or rhabdomyolysis, respectively. Most cases of nephrotoxic ATN from exogenous toxins
are associated with antimicrobial agents such as aminoglycosides and amphotericin B, radiocon-
trast media, and chemotherapeutic agents including cisplatinum and ifosfamide. From a clinical
perspective, patients are often divided into oliguric and nonoliguric. Oliguria is defined as urine
output less than 500 mL/day. Patients without oliguria typically have a better prognosis (Thadhani
et al., 1996).
The pathogenesis of ischemic ATN can be divided into several phases. There usually is an ini-
tiation phase characterized by epithelial and endothelial cell injury. Cell injury is most often seen
in the proximal tubule and the medullary portion of the thick ascending limb of the loop of Henle.
These segments are very metabolically active and are located in the outer medulla, which has low
oxygen tensions and hence most susceptible to injury. The initiation phase is followed by an exten-
sion phase, independent of the initial ischemic insult, mediated by microvascular endothelial injury
and activation of inflammatory pathways. This phase is followed by a maintenance phase, during
which the epithelial and endothelial cells undergo repair and redifferentiation, followed by recovery
of renal function (Norbert, 2005).
Several mechanisms are thought to underlie the reduction in GFR during ATN. There is pro-
found vasoconstriction, mediated directly by endothelial injury and indirectly through tubuloglo-
merular feedback, resulting in a direct reduction in glomerular filtration. In addition, sloughing of
cells from the tubular epithelium denudes the tubular basement membrane and leads to formation
of intratubular casts. These casts cause tubular obstruction, and the denuded basement membrane
permits back leak of glomerular filtrate (Khalil et al., 2008).
60 Nutrition Therapy for Chronic Kidney Disease
The clinical course of ATN can be highly variable. There is typically an initial oliguric phase,
beginning within 24 h of the inciting event and lasting 13 weeks, followed by a diuretic phase
characterized by a progressive increase in urine volume that is usually indicative of renal recovery.
Many patients, however, may be nonoliguric throughout their course.
4.3.3.3 Glomerulonephritis
The two types of glomerulonephritis that cause AKI are rapidly progressive glomerulonephritis and
acute proliferative glomerulonephritis. In primary glomerulonephritis, disease is almost entirely
restricted to the kidneys (as in IgA nephropathy or poststreptococcal glomerulonephritis), whereas
in secondary glomerulonephritis it occurs in association with more diffuse inflammation (as in
systemic lupus erythematosus or systemic vasculitis). The hallmark findings of GN-associated AKI
are related to damage to the glomerular basement membrane (GBM) and glomerular bleeding.
Besides hematuria, patients usually have hypertension, edema, and proteinuria. Serologic studies
and a renal biopsy assist in making the diagnosis. The specific findings on kidney biopsy depend on
the underlying glomerular process; proliferative lesions in the glomerulus are characteristic. Prompt
recognition of these entities is critical because prompt initiation of therapy is essential to preserve
kidney function and prevent irreversible renal damage.
TABLE 4.5
Urinary Indices in Prerenal Azotemia and Acute Tubular Necrosis
Index Prerenal Acute Tubular Necrosis
Urinary sodium (mEq/L) <20 >40
Fractional excretion of sodium (%)a <1 >2
Urine osmolality (mOsm/L) >500 <350
BUN/Serum creatinine ratio >20:1 10:1
Fractional excretion of urea (%)b <35 >50
the urine is similar in osmolality to plasma, and urinary sodium is high. The fractional excretion of
sodium (FENa) is a commonly used index in differentiating prerenal azotemia and ATN. FENa is
the percentage of the sodium filtered by the kidney that is excreted in the urine. The use of diuretics
can decrease the sensitivity of FENa by inhibiting tubular sodium reabsorbtion. In contrast, the frac-
tional excretion of urea nitrogen (FEUN) is primarily dependent on passive forces and is therefore
less influenced by diuretic therapy. Thus, in some studies, a low FEUN (35%) has been found to be
consistent with a diagnosis of prerenal azotemia (Carvounis et al., 2002). The ultimate determination
of whether a patient has prerenal or intrinsic AKI may require a diagnostic trial of intravenous fluids.
The differences between prerenal azotemia and ATN are highlighted in Table4.5.
The urinalysis is an extremely useful tool in the diagnosis. The urine is typically bland in
prerenal azotemia and postrenal etiologies. The presence of dysmorphic red blood cells and red-
blood-cell casts is strongly indicative of an acute glomerular process. The presence of heme-
positive urine with no red blood cells on microscopy suggests rhabdomyolysis or hemolysis. The
presence of white blood cells, white-blood-cell casts, and eosinophiluria supports the diagnosis of
AIN. Tubular epithelial cells and muddy brown granular casts are present in ATN. Heavy oxalate
or uric acid crystalluria or the presence of drug crystals suggests intratubular crystal deposition,
and the presence of nonalbumin proteinuria suggests a diagnosis of myeloma kidney.
Eosinophilia may be seen in atheroembolic disease, acute interstitial nephritis, or ChurgStrauss
disease. Thrombocytopenia and fragmented red cells suggest the diagnosis of a microangiopathy,
such as thrombotic thrombocytopenic purpura, hemolytic uremic syndrome, disseminated intravas-
cular coagulation, malignant hypertension, or scleroderma renal crisis. Serological studies including
antistreptolysin-O titers, antinuclear antibodies, antineutrophil cytoplasmic antibody, anti-GBM anti-
bodies, and complement levels are indicated to diagnose certain vasculitis and glomerulonephritis.
A kidney biopsy may be indicated when the diagnosis remains uncertain, especially if there is
suspicion of acute glomerulonephritis or acute interstitial nephritis or if there is failure of kidney
function to improve.
be directed to prevent further volume/blood loss. Patients, especially those with cardiac compro-
mise, oliguria, or elderly patients, need to be closely monitored during aggressive fluid resuscitation.
Some patients may need invasive hemodynamic monitoring with either a central venous catheter or
a Swan-Ganz catheter to guide therapy.
Prerenal azotemia is often seen in congestive heart failure. Optimizing the treatment of heart
failure can improve kidney perfusion. Sometimes, especially with advanced heart failure, one has to
accept some amount of prerenal azotemia. In hospitalized patients who have decompensated heart
failure, inotropic agents such as dobutamine or milrinone, or vasodilators such as nitroglycerine,
nitroprusside, or nesiritide may be used to optimize renal perfusion, although usually such treat-
ment are only a temporizing measure (House et al., 2010).
Hepatorenal syndrome needs to be differentiated from volume depletion and a host of other con-
ditions. Rehydration and intravenous albumin are often used in such patients. The definitive cure
lies in either liver transplantation or spontaneous recovery of the diseased liver. The use of drugs
that induce splanchnic vasoconstriction (octreotide) and renal vasodilatation (midodrine) have been
beneficial in treating hepatorenal syndrome. Some patients benefit from transjugular intrahepatic
portosystemic shunts, which cause a decrease in the portal pressures.
Severe malnutrition can be seen in as many as 42% patients with AKI. Protein energy wasting
is associated with an increased risk of complications like sepsis, bleeding and arrhythmias, and
heightened mortality (Fiaccadori et al., 1999). Nutritional therapy should not only cover the energy,
protein, and micronutrient requirements but also preserve lean body mass and support immune
function and wound healing.
(VLDL) and low-density lipoproteins increases. The total cholesterol and HDL levels decrease
(Druml, 2005; Fiaccadori et al., 2008). The activity of both peripheral lipoprotein lipase and hepatic
triglyceride lipase is reduced by about 50% and this causes impairment of lipolysis. Metabolic aci-
dosis that frequently accompanies AKI in the hospital setting also causes inhibition of lipoprotein
lipase and impairment of lipolysis. In addition, the clearance of the infused lipids is reduced in
patients receiving parenteral nutrition.
4.10.5 Electrolytes
4.10.5.1 Potassium
Potassium levels are frequently abnormal in patients with AKI. The impairment of potassium
excretion frequently occurs with oliguric kidney failure. The contribution of increased cell death
and turnover and increased extracellular shifts as a result of acidosis are also contributing factors.
Hypokalemia may also occur in patients with ARF because of the use of diuretics and during the
recovery phase of ATN, especially if potassium intake is restricted. Dialytic therapies are very
effective in controlling hyperkalemia in most patients with AKI.
4.10.5.2 Phosphorus
Phosphorus levels are usually high in patients with kidney failure. The impaired renal excretion
along with increased release from the cells and increased bone turnover all contribute to the pro-
cess. Usually patients with AKI will need binders to reduce serum phosphorus levels.
The duration of dialysis is a significant factor in determining the clearance of phosphorus.
Increasing the duration of dialysis treatment typically increases clearance of phosphorus. Continuous
RRTs commonly cause hypophosphatemia requiring replacement.
4.10.5.3 Calcium
Calcium has a variety of roles that go beyond bone metabolism. It helps to maintain the electrophys-
iological characteristics of both the smooth muscles and the cardiac muscles and plays an important
role in blood coagulation and platelet adhesion. Most patients with AKI develop hypocalcemia.
Patients with AKI usually have hyperphosphatemia along with hypocalcemia because of impaired
production of 1, 25 dihydroxy vitamin D. The decreased intestinal calcium absorption and skeletal
resistance to parathyroid hormone are also thought to play a part. On the other hand, immobilization
leads to hypercalcemia. Other contributing factors include calcium concentrations in the dialysate
and hyperparathyroidism. Severe hypocalcemia may be seen in acute pancreatitis and rhabdomy-
olysis due to precipitation of calcium. Conditions like multiple myeloma and milk alkali syndrome
can cause AKI as well as hypercalcemia.
Calcium levels should always be interpreted in the light of albumin levels and the acid-base sta-
tus. It may be beneficial to obtain an ionized calcium level.
4.10.5.4 Magnesium
Reduced magnesium excretion is typically seen with oliguric AKI. Hypermagnesemia in patients
with AKI usually tends to be mild unless there is evidence of rapid cell breakdown. The symp-
toms of hypermagnesemia are usually related to neuromuscular irritability or cardiac arrhythmias.
Treatment usually involves intravenous calcium, which can rapidly resolve these symptoms. RRT
can be used to control hypermagnesemia. Low serum magnesium levels are seen as side effects of
some medications. Loop diuretics and certain nephrotoxic drug, such as amphotericin and cispla-
tin, are associated with urinary magnesium wasting. Hypomagnesemia may develop in patients on
CRRT owing to dialytic losses with prolonged duration of therapy. These can be easily treated with
oral or parenteral replacement.
4.10.6 Vitamins
The levels of water-soluble vitamins are generally low in patients with AKI who require dialysis
support. These vitamins are mainly lost in the dialysate and need to be replaced. The magnitude of
loss varies and can be significant, with up to 100 mg of vitamin C being lost per day in the dialysate.
The losses can be even higher when continuous RRT are used and higher intakes of vitamin C up
to 150200 mg/day are needed. However, the metabolism of vitamin C is different from most other
water-soluble vitamins, as its metabolic products can accumulate and cause secondary oxalosis. The
68 Nutrition Therapy for Chronic Kidney Disease
total intake of vitamin C should not exceed 250 mg/day. Significant losses of B vitamins including
thiamine tend to occur during renal replacement therapies (Wooley et al., 2005). In general, patients
on dialysis and severely malnourished patients should receive double the normal dose of water-
soluble vitamins.
Some of the fat-soluble vitamins can also be deficient, especially vitamin D, which depends on
the kidneys to be hydoxylated to the active form. The levels of vitamin A and E can also be low
in AKI patients. However, hypervitaminosis A has been recently documented in pediatric patients
with AKI on RRT (Lipkin and Lenssen, 2008). Vitamin K does not need any special replacement
in patients with AKI as its levels are generally increased in patients with AKI.
UNA (g/day) = UUN (g/day) + dialysate urea nitrogen (g/day) + change in body urea nitrogen
(g/day)
Change in body urea nitrogen (g/day) = [(BUNf BUNi) BWi 0.6 L/kg] + [(BWf BWi)
BUNf 1 L/kg],
where i and f represent the initial (immediately after dialysis) and final (immediately before the
second dialysis session) values for the period of measurement. The factor of 0.6 is an estimate of the
fraction of adult body weight as water, and 1.0 is the fractional distribution of urea in the gained or
lost weight (Btaiche et al., 2008).
Protein catabolic rate (PCR) is a measure of net protein degradation. PCR is based on edema-
free body cell mass. It can be normalized to protein degraded divided by the dry body weight and
is labeled as normalized PCR (nPCR). PCR is calculated as
The limitations of wide applicability of nPCR are due to its variable values in metabolically unsta-
ble patients and its rapid fluctuations with changes in protein intake. It also tends to underestimate
Acute Kidney Injury 69
protein intake when the intake is high and overestimates it when protein intake is less than 1 g/kg/
day. It tends to be most accurate in state of equilibrium, and in critically ill patients daily measure-
ments of PCR are sometimes needed to make an accurate assessment (Btaiche et al., 2008). Higher
PCR is expected in highly catabolic patients such as those with severe burn injuries.
Even in patients who are unable to tolerate enteral feeding effectively to maintain their nutri-
tional needs, trophic feedings to maintain gut mucosa are used effectively to decrease the risk of
bacterial translocation and risk of infections. The combination of parenteral nutrition to provide the
nutritional requirements and the enteral feedings for trophic purposes should be considered as they
complement each other.
The electrolyte balance is usually controlled efficiently in patients on dialysis. In patients under-
going CRRT, replacement of electrolytes like phosphorus and magnesium may be required.
REFERENCES
Abernethy, V. and Lieberthal, W. 2002. Acute renal failure in the critically ill patient. Crit Care Clin, 18,
203222.
Basi, S., Pupim, L., Simmons, E., et al. 2005. Insulin resistance in critically ill patients with acute renal failure.
Am J Physiol Renal Physiol, 289, F259F264.
Bell, M. 2008. Acute kidney injury: New concepts, renal recovery. Nephron Clin Pract, 109, c224c228.
Bellomo, R., Ronco, C., Kellum, J., et al. 2004. Acute renal failureDefinition, outcome measures, animal
models, fluid therapy and information technology needs: The Second International Consensus Conference
of the Acute Dialysis Quality Initiative (ADQI) Group. Crit Care, 8, R204R212.
Btaiche, I., Mohammad, R., Alaniz, C., et al. 2008. Amino acid requirements in critically ill patients with acute
kidney injury treated with continuous renal replacement therapy. Pharmacotherapy, 28, 600613.
Carvounis, C., Nisar, S. and Guro-Razuman, S. 2002. Significance of the fractional excretion of urea in the
differential diagnosis of acute renal failure. Kidney Int, 62, 22232229.
Casey, E., Gupta, B., Erwin, P., et al. 2010. The dose of continuous renal replacement therapy for acute renal
failure: A systematic review and meta-analysis. Renal Fail, 32, 555561.
Cerda, J., Bagga, A., Kher, V., et al. 2008. The contrasting characteristics of acute kidney injury in developed
and developing countries. Nat Clin Pract Neph, 4, 138153.
Dancona, G., Bertuzzi, F., Sacchi, L., et al. 2011. Iatrogenic hypoglycemia secondary to tight glucose control is
an independent determinant for mortality and cardiac morbidity. Eur J Cardiothorac Surg, 40, 360366.
Davenport, A., Bouman, C., Kirpalani, A., et al. 2008. Delivery of renal replacement therapy in acute kidney
injury: What are the key issues? Clin J Am Soc Nephrol, 3, 869875.
Druml, W. 2005. Nutritional management of acute renal failure. J Ren Nutr, 15, 6370.
Faisy, C., Guerot, E., Diehl, J., et al. 2003. Assessment of resting energy expenditure in mechanically ventilated
patients. Am J Clin Nutr, 78, 241249.
Fiaccadori, E., Lombardi, M., Leonardi, S., et al. 1999. Prevalence and clinical outcome associated with pre-
existing malnutrition in acute renal failure: A prospective cohort study. J Am Soc Nephrol, 10, 581593.
Fiaccadori, E., Parenti, E. and Maggiore, U. 2008. Nutritional support in acute kidney injury. J Nephrol, 21,
645656.
Hoste, E. and Schurgers, M. 2008. Epidemiology of acute kidney injury: How big is the problem? Crit Care
Med, 36, S146S151. DOI: 10.1097/CCM.0b013e318168c590.
House, A., Haapio, M., Lassus, J., et al. 2010. Therapeutic strategies for heart failure in cardiorenal syndromes.
Am J Kid Dis Off J Natl Kid Found, 56, 759773.
Khalil, P., Murty, P. and Palevsky, P. 2008. The patient with acute kidney injury. Prim Care, 35, 239264, vi.
Klahr, S. and Miller, S. 1998. Acute oliguria. N Engl J Med, 338, 671675.
72 Nutrition Therapy for Chronic Kidney Disease
Kronzon, I. and Saric, M. 2010. Cholesterol embolization syndrome. Circulation, 122, 631641.
Lipkin, A. and Lenssen, P. 2008. Hypervitaminosis A in pediatric hematopoietic stem cell patients requiring
renal replacement therapy. Nutr Clin Pract, 23, 621629.
Loo, M., Felsen, D., Weisman, S., et al. 1988. Pathophysiology of obstructive nephropathy. World J Urol, 6,
5360.
Macias, W., Alaka, K., Murphy, M., et al. 1996. Impact of the nutritional regimen on protein catabolism and
nitrogen balance in patients with acute renal failure. J Parenter Enteral Nutr, 20, 5662.
Mouser, J., Hak, E., Kuhl, D., et al. 1997. Recovery from ischemic acute renal failure is improved with enteral
compared with parenteral nutrition. Crit Care Med, 25, 17481754.
Norbert, L. 2005. The pathophysiology of acute renal failure. Crit Care Clin, 21, 197210.
Palevsky, P. 2006. Unresolved issues in dialysis: Dialysis modality and dosing strategy in acute renal failure.
Semin Dialysis, 19, 165170.
Passadakis, P. and Oreopoulos, D. 2007. Peritoneal dialysis in patients with acute renal failure. Adv Perit Dial,
23, 716.
Praga, M. and Gonzalez, E. 2010. Acute interstitial nephritis. Kidney Int, 77, 956961.
Rao, A., Chouhan, V., Chen, X., et al. 1999. Activation of the tissue factor pathway of blood coagulation during
prolonged hyperglycemia in young healthy men. Diabetes, 48, 11561161.
Schetz, M., Vanhorebeek, I., Wouters, P., et al. 2008. Tight blood glucose control is renoprotective in critically
ill patients. J Am Soc Nephrol, 19, 571578.
Srisawat, N., Hoste, E., Kellum, J. 2010. Modern classification of acute kidney injury. Blood Purif, 29, 300307.
Thadhani, R., Pascual, M., Bonventre, J. 1996. Acute renal failure. N Engl J Med, 334, 14481460.
Wernerman, J. 2008. Clinical use of glutamine supplementation. J Nutr, 138, 2040S2044S.
Wooley, J., Btaiche, I. and Good, K.005. Metabolic and nutritional aspects of acute renal failure in critically ill
patients requiring continuous renal replacement therapy. Nutr Clin Pract, 20, 176191.
Yarlagadda, S. and Perazella, M. 2008. Drug-induced crystal nephropathy: An update. Expert Opin Drug Saf,
7, 147158.
5 Nephrotic Syndrome
Tai-Gen Cui
Capital Medical University
CONTENTS
5.1 Introduction............................................................................................................................. 73
5.2 Etiology.................................................................................................................................... 74
5.3 Clinical Features and Pathogenesis......................................................................................... 74
5.3.1 Glomerular Injury and Proteinuria.............................................................................. 74
5.3.2 Hypoalbuminemia....................................................................................................... 75
5.3.3 Urinary Loss of Other Plasma Proteins and Their Functional
Consequences.............................................................................................................. 75
5.3.4 Hyperlipidemia............................................................................................................ 75
5.3.5 Edema.......................................................................................................................... 75
5.4 Complications.......................................................................................................................... 76
5.4.1 Acute Renal Failure..................................................................................................... 76
5.4.2 Thromboembolism...................................................................................................... 76
5.4.2.1 Infection........................................................................................................ 76
5.4.3 Protein Malnutrition.................................................................................................... 76
5.5 Diagnosis................................................................................................................................. 76
5.6 Treatment................................................................................................................................. 77
5.6.1 Nutritional Therapy..................................................................................................... 77
5.6.2 Proteinuria Treatment.................................................................................................. 77
5.6.3 Edema Treatment......................................................................................................... 77
5.6.4 Hyperlipidemia Treatment........................................................................................... 78
5.6.5 Hypercoagulability Treatment..................................................................................... 78
5.6.6 Specific Therapy.......................................................................................................... 78
References......................................................................................................................................... 78
5.1 INTRODUCTION
Nephrotic syndrome (NS) refers to a group of diseases characterized by heavy proteinuria, hypoal-
buminemia, hyperlipidemia, and edema. It is usually classified as primary or secondary. Primary
nephrotic syndrome is also known as idiopathic nephrotic syndrome, which is caused by a variety
of primary glomerular diseases. In secondary nephrotic syndrome, kidney disease is part of an
identifiable systemic disease (Orth and Ritz, 1998). Although nephrotic syndromes can be caused by
various diseases, they have one common featureinjury to the glomerular filtration barrier result-
ing in the loss of a large amount of plasma protein in the urine and subsequent metabolic disorders
(Falk, 2004).
73
74 Nutrition Therapy for Chronic Kidney Disease
5.2 ETIOLOGY
Theoretically, any injury to the glomerular capillary wall, regardless of etiology, may result in
nephrotic syndrome. Patients with this syndrome typically have proteinuria with an otherwise bland
urine sediment. Several systemic diseases such as diabetes mellitus and systemic lupus erythema-
tosus or amyloidosis are associated with nephrotic syndrome. This syndrome can also be associated
with primary renal disorders such as minimal change disease (MCD) (seen mostly in children),
focal segmental glomerulosclerosis (FSGS), or membranous nephropathy. However, FSGS and
membranous nephropathy can also be secondary to systemic diseases. Other nephritides such as
membranoproliferative glomerulonephritis or IgA nephropathy can cause nephrotic syndrome, but
patients with this type of nephrotic syndrome have an active urine sediment with red blood cells
(RBCs) or RBC casts frequently found on microscopic analysis of urine (Myers et al., 1982).
The most common etiology of nephrotic syndrome varies according to age. In children with
nephrotic syndrome, 90% of those below 10 years and 50% of those above 10 years will have
MCD (A Report of the International Study of Kidney Disease in Children, 1978). Patients with
MCD have findings of diffuse foot process effacement on electron microscopy and otherwise
unremarkable changes on light microscopy. Adults with idiopathic nephrotic syndrome are most
likely to have FSGS, which is found in about 35% of cases in the United States and 50% of
cases among black adults (Haas et al., 1997). FSGS can be either primary or secondary, and it is
very important to differentiate the types, as they require very different treatments. Membranous
nephropathy is another common etiology of nephrotic syndrome in adults and can be either
primary or secondary. Specific treatment and outcome of nephrotic syndrome depend on its
etiology.
5.3.2 Hypoalbuminemia
Serum albumin falls as a consequence of proteinuria. In nephrotic syndrome, the serum albumin
level usually drops below 30 g/L. Generally, hepatic albumin synthesis increases in response to
albumin loss in an attempt to normalize plasma albumin concentration (Ballmer et al., 1992).
Usually, however, the increased synthesis is unable to compensate for the loss of albumin due to
nephrotic syndrome. More importantly, since there is a substantial increase in renal tubular cell
catabolism of filtered proteins in nephrotic syndrome, the urinary protein excretion rate will not be
an accurate measure of the protein loss.
5.3.4 Hyperlipidemia
Hyperlipidemia is another typical feature of nephrotic syndrome. The abnormalities of lipid pro-
file in nephrotic syndrome include hypercholesterolemia and hypertriglyceridemia with increases
in both low-density lipoproteins (LDL) swelling and very low-density lipoproteins (VLDL).
Decreased plasma osmotic pressure appears to stimulate hepatic lipoprotein synthesis, resulting
in hypercholesterolemia. In addition, a defect in the LDL receptor results in a diminished clear-
ance of LDL. Impaired metabolism rather than increased synthesis is responsible for hypertri-
glyceridemia (de Sain-vander Velden et al., 1998). Hyperlipidemia in nephrotic syndrome is an
independent risk factor for atherosclerotic cardiovascular disease; it also aggravates renal disease
and is associated with thrombosis.
5.3.5 Edema
Edema is the most common symptom of nephrotic syndrome. Fluid retention is limited mainly to
the interstitial compartment. The severity of edema usually parallels the degree of hypoalbumin-
emia. Edema may manifest as periorbital swelling and/or bilateral pitting edema of legs. Also,
pleural effusion and ascites are not uncommon in nephrotic patients and, in severe cases, anasarca
and even pulmonary edema may occur. Two mechanisms have been proposed to explain the occur-
rence of edema in nephrotic syndrome. In some patients, a decrease in plasma osmotic pressure
resulting from a low serum albumin level is thought to be the primary cause of fluid accumulation
in the interstitial space; subsequent water and sodium retention is caused by activation of the ner-
vous and endocrine systems secondary to a reduction in the effective circulatory volume. In other
patients, there is a corresponding fall in the interstitial protein concentration and little change in the
transcapillary osmotic pressure gradient, and circulatory volume is normal or even high. In these
76 Nutrition Therapy for Chronic Kidney Disease
patients, edema appears to be the consequence of primary renal sodium retention in the collecting
tubules (Ichikawa et al., 1983).
5.4 COMPLICATIONS
5.4.1 Acute Renal Failure
Acute renal failure can occur in some patients with nephrotic syndrome, particularly in those with
a pathological type of MCD (Jennette and Falk, 1990). Its mechanism is not fully understood.
Certain drugs, including antibiotics, diuretics, angiotensin-converting enzyme inhibitors (ACEIs),
and nonsteroidal anti-inflammatory drugs (NSAIDs), may cause acute kidney injury by inducing
acute tubulointerstitial nephritis. Bilateral renal vein thrombosis (RVT) may cause acute renal
failure. Two other conditions are (1) collapsing FSGS, in which tubular injury is thought to play an
important role, and (2) crescentic glomerulonephritis superimposed on membranous nephropathy,
in which active urine sediment can be found. Acute renal failure may occur without any identifi-
able cause; several factors, including hypovolemia, interstitial edema, and ischemic tubular injury,
have been suggested for this (Smith and Hayslett, 1992).
5.4.2 Thromboembolism
Patients with nephrotic syndrome have a greater risk of thromboembolism, particularly DVT and
RVT. Cerebral vein thrombosis has been rarely reported. Although the mechanism of hypercoagu-
lability has not been completely understood, it may be related to changes in plasma coagulation
factors. Several other factors may also be involved, including hypovolemia, hyperlipidemia, and the
use of diuretics, all of which lead to increased blood viscosity (Llach, 1985).
RVT occurs disproportionately in patients with membranous nephropathy. Acute RVT often
presents with flank pain, gross hematuria, and a decline in renal function. However, most patients
with RVT are asymptomatic, and RVT is suspected only when pulmonary thromboembolism devel-
ops. Although pulmonary thromboembolism is not common, it can be fatal.
5.4.2.1 Infection
Patients with nephrotic syndrome are susceptible to infection. Before the advent of antibiotics,
infection was the leading cause of death in children with nephrotic syndrome (Taube et al., 1984).
Pneumococcal infections, especially peritonitis, were particularly common (Krensky et al., 1982).
Urinary tract and lung infections may also occur in nephrotic patients. Here too, the process of
impairment of the normal defense mechanism of the body is not well understood. However, low
levels of IgG due to urinary losses and decreased synthesis of IgG may be the reason (Heslan et al.,
1982). Also, glucocorticoid and immunosuppressive drugs used for treating nephrotic syndrome
predispose patients to infection.
5.5 DIAGNOSIS
Diagnosis of nephrotic syndrome is not difficult. Criteria include the presence of nephrotic-range
proteinuria, in which urinary protein excretion rate exceeds 3.5 g/day as determined by 24-h
Nephrotic Syndrome 77
urinary protein excretion, hypoalbuminemia (serum albumin level below 30 g/L), hyperlipidemia,
and edema. Among these criteria, the first two are required for a confirmed diagnosis. However,
one should not be content with the presence of such criteria, which can by caused by various other
primary glomerular diseases or systemic diseases. A thorough knowledge of the patients history,
physical examination, and further serologic studies are needed, and in most cases, a kidney biopsy
is usually required to establish the final diagnosis.
5.6 TREATMENT
Nephrotic syndrome calls for nonspecific and specific treatments. Nonspecific treatment aims at
alleviating nutritional deficiencies, treating proteinuria, edema, hyperlipidemia, and hypercoagu-
lability. Antiproteinuric medications such as angiotensin receptor blockers (ARBs) and ACEIs are
often the mainstay of nonspecific treatment. Specific treatment aims at the underlying causes, which
are determined by kidney biopsy, and can include steroids and immunosuppressant medications.
5.6.6Specific Therapy
Patients with secondary nephrotic syndrome who have clearly identifiable etiology found by biopsy
should receive specific treatment aimed at the underlying causes. For primary nephrotic syndrome,
pathological findings are of prime importance in determining the proper therapeutic regimen.
Although glucocorticoids are often used to treat nephrotic syndrome, cytotoxic drugs or immuno-
suppressive agents are also used either alone or in combination with glucocorticoids based on the
pathological results. Specific treatments for individual etiologies of nephrotic syndrome are beyond
the scope of this book. However, special attention should be paid to monitoring closely the adverse
effects such as infection, elevation in blood sugar, or other comorbidities that occur with steroid
treatment or other immunosuppressant medications.
REFERENCES
A Report of the International Study of Kidney Disease in Children. 1978. Nephrotic syndrome in children:
Prediction of histopathology from clinical and laboratory characteristics at time of diagnosis. Kidney Int.
13:159.
Ballmer, P., Weber, B., Roy-Chaudhury, P., et al. 1992. Elevation of albumin synthesis rates in nephrotic patients
measured with [113C] leucine. Kidney Int. 41:132138.
Castellino, P. and Cataliotti, A. 2002. Changes of protein kinetics in nephrotic patients. Curr Opin Clin Metab
Care. 5:5154.
DAmico, G., Gentile, M., Manna, G., et al. 1992. Effect of vegetarian soy diet on hyperlipidemia in nephrotic
syndrome. Lancet. 339:11311134.
de Sain-vander Velden, M., Kaysen, G., Barrett, H., et al. 1998. Increased VLDL in nephrotic patients
results from a decreased catabolism while increased LDL results from increased synthesis. Kidney Int.
53:9941001.
Falk, R. 2004. Primary Glomerular Disease. Brenner BM, Rector FC. The Kidney, 7th edition. Philadelphia,
PA: WB Saunders.
Feinstein, E., Kaptein, E., Nicoloff, J., et al. 1982. Thyroid function in patients with nephrotic syndrome and
normal renal function. Am J Nephrol. 2:7076.
Haas, M., Meehan, S., Karrison, T., et al. 1997. Changing etiologies of unexplained adult nephrotic syndrome:
A comparison of renal biopsy findings from 19761979 and 19951997. Am J Kidney Dis. 30:621.
Heeg, J., de Jong, P., van der Hem, G., et al. 1987. Reduction of proteinuria by angiotensin converting enzyme
inhibition. Kidney Int. 32:7883.
Heslan, J., Lautie, J., Intrator, L., et al. 1982. Impaired IgG synthesis in patients with nephrotic syndrome.
Clinical Nephrol. 18:144147.
Ichikawa, I., Rennke, H., Hover, J., et al. 1983. Role for intrarenal mechanisms in the impaired salt excretion
of experimental nephrotic syndrome. J Clin Invest. 71:91103.
Nephrotic Syndrome 79
Jennette, J. and Falk, R. 1990. Adult minimal change glomerulopathy with acute renal failure. Am J Kidney
Dis. 16:432437.
Kendall, A., Lohmann, R., Dossetor, J. 1971. Nephrotic syndrome. A hypercoagulable state. Arch Intern Med.
127:10211027.
Koening, K., Lindeberg, J., Zerwekh, J., et al. 1992. Free and total 1,25-dihydroxyvitamin D levels in subjects
with renal disease. Kidney Int. 41:161165.
Krensky, A., Ingelfinger, J., Grupe, W. 1982. Peritonitis in childhood nephrotic syndrome. Am J Dis Child.
136:732736.
Llach, F. 1985. Hypercoagulability, renal vein thrombosis, and other thrombotic complications of nephrotic
syndrome. Kidney Int. 28:429.
Myers, B., Okarma, T., Friedman, S., et al. 1982. Mechanisms of proteinuria in human glomerulonephritis.
JClin Invest. 70:732746.
Nath, K., Kre, S., Hostetter, T. 1986. Dietary protein restriction in established renal injury in the rat: Selective
role of glomerular capillary pressure in progressive glomerular dysfunction. J Clin Invest. 78:11991205.
Orth, S. and Ritz, E. 1998. The nephrotic syndrome. N Engl J Med. 338:1202.
Praga, M. ,Hernandez, E., Montoyo, C., et al. 1992. Long-term beneficial effects of angiotensin-converting
enzyme inhibition in patients with nephrotic proteinuria. Am J Kidney Dis. 20:240248.
Smith, J. and Hayslett, J. H. 1992. Reversible renal failure in the nephrotic syndrome. Am J Kidney Dis.
19:201213.
Taube, D., Brown, Z., Williams, D. 1984. Impaired lymphocyte and suppressor cell function in minimal
change nephropathy, membranous nephropathy and focal segmental glomerulonephritis. Clin Nephrol.
22:176782.
Vega, G. and Grundy, S. 1988. Lovastatin therapy in nephrotic hyperlipidemia: Effects on lipoprotein metabo-
lism. Kidney Int. 33:11601168.
Wheeler, D., Nair, D., Persaud, J., et al. 1991. Effects of dietary fatty acids in an animal model of focal glo-
merulosclerosis. Kidney Int. 39:930937.
6 Current Techniques for Dialysis
Jennifer Othersen
WJB Dorn VA Medical Center
and University of South Carolina School of Medicine
CONTENTS
6.1 Introduction............................................................................................................................. 81
6.2 Vascular Access Planning....................................................................................................... 81
6.3 The Dialysis Decision.............................................................................................................. 82
6.3.1 Benefits........................................................................................................................ 83
6.4 Modality Selection................................................................................................................... 83
6.4.1 Peritoneal Dialysis.......................................................................................................84
6.4.2 Types of Peritoneal Dialysis........................................................................................ 85
6.4.3 Complications.............................................................................................................. 85
6.4.4 Adequacy of Dialysis................................................................................................... 86
6.4.5 Nutrition....................................................................................................................... 86
6.5 Hemodialysis........................................................................................................................... 86
6.6 Vascular Access.......................................................................................................................90
6.7 Continuous Renal Replacement Therapy................................................................................90
6.8 Outcomes in Dialysis...............................................................................................................90
6.9 Summary................................................................................................................................. 91
References......................................................................................................................................... 91
6.1 INTRODUCTION
The decision to initiate hemodialysis is a complex one. Many factors must be considered, and the
patient must be fully involved. According to the National Kidney Foundation Kidney Disease
Outcomes Quality Initiative (KDOQI) guidelines, patients should be referred to a nephrologist
when their glomerular filtration rate (GFR) is less than 30 (National Kidney Foundation, 2000).
However, some patients have been shown to benefit from earlier referral, whereas late referral to a
nephrologist has been shown to be strongly associated with early death in patients with end-stage
renal disease (Kessler et al., 2003). Patients with rapidly changing renal function, proteinuria, or
evidence of glomerular disease should be immediately referred to a nephrologist. Nephrologists
are able to evaluate the etiology of renal disease as well as treat the multiple comorbidities, thereby
improving outcomes. Early referral to a nephrologist also allows the patient and nephrologist time
to develop a relationship. It is essential that patients be fully educated about chronic kidney disease
(CKD) and the expected progression of their disease. This allows for patient-centered care and
patient participation in the decision-making process.
81
82 Nutrition Therapy for Chronic Kidney Disease
Artery
Vein
Blood to dialysis
Blood from dialysis machine
machine Graft
FIGURE 6.1 Access for dialysis. (From Guniita/Dreamstime.com, Dreamstime USA Headquarters,
Brentwood, TN. With permission.)
anticipated need for dialysis (Figure 6.1; National Kidney Foundation, 2002). By the time patients
meet these criteria, discussions should have occurred about the patients wishes regarding dialysis
and preference for dialysis modality. Ideally, patients should participate in formal dialysis educa-
tion that provides information about the different modalities of dialysis, access to the various types
of dialysis, and transplantation options. There are excellent online resources for patients if formal
dialysis education is not an option. It is not uncommon for patients to initially refuse dialysis or
dialysis access placement. However, after appropriate patient education or development of symp-
toms due to progression of disease, patients who initially refuse dialysis often decide to proceed
with renal replacement therapy (RRT). Providers should be prepared to have continuing discussions
with their patients regarding dialysis and dialysis planning. Outcomes are improved for patients
who participate in early hemodialysis planning. It is important that all members of the health care
team be involved in patient education, including nephrologists, nursing staff, social workers, vascu-
lar surgeons, and dieticians.
No dialysis Dialysis
Choose
modality
FIGURE 6.2 Decision stages leading to dialysis. (From Guniita/Dreamstime.com, Dreamstime USA
Headquarters, Brentwood, TN. With permission.)
6.3.1 Benefits
Dialysis may be used for correction of electrolyte abnormalities or acidosis, for clearance of uremic
or other toxins from the body, and ultrafiltration or removal of excess fluids. Resolution of uremic
symptoms with adequate dialysis often results in an increase of patients oral intake and thus improve-
ment of their nutritional status. Associated comorbidities such as anemia, iron deficiency, and renal
osteodystrophy are often treated with medications during dialysis. In addition, nutritional status, lipid
profiles, hypertension, and diabetes are monitored regularly as part of dialysis care. Many dialysis cen-
ters offer nutritional supplementations in conjunction with careful monitoring by the centers dietician.
In making a choice between hemodialysis and peritoneal dialysis, several factors must be con-
sidered, of which the first is availability. Peritoneal dialysis is only an option if there is a peritoneal
dialysis program available with a staff that is capable of training patients and having someone avail-
able to troubleshoot problems that may arise at home. Patients who live in rural areas may not have
easy access to in-center dialysis and may have difficulty traveling to the center three times a week
for hemodialysis. Individual patient characteristics, such as the patients medical comorbidities,
compliance, ability to obtain vascular access, and social support, must also be considered.
FIGURE 6.3 Steps for peritoneal dialysis. (Courtesy of the National Institute of Diabetes and Digestive and
Kidney Diseases, National Institutes of Health.)
Current Techniques for Dialysis 85
near those in the blood. At this point, the fluid should be exchanged, as the clearance or diffusion of sol-
utes is much less effective. This loss of concentration gradient is what necessitates repeated exchanges
of dialysate fluid. The transport characteristics of the peritoneal membrane can be determined using
the peritoneal equilibration test. The results are then used to individualize a patients prescription for
peritoneal dialysis. High or rapid transporters require short dwells with frequent exchanges. Low or
slow transporters have a less efficient membrane for exchange, and this results in the slower transport
of solutes. Therefore, low transporters may require longer dwells.
In peritoneal dialysis, ultrafiltration of fluid (volume removal) is achieved using the osmotic force
created by high osmolality dialysate solutions. Low (slow) transporters are more successful in obtain-
ing adequate ultrafiltration because they maintain the osmotic gradient for a longer period, allowing
better removal of fluid. High (rapid) transporters have a more rapid absorption of the solutes that cre-
ate the osmotic gradient and therefore have more difficulty achieving adequate ultrafiltration.
6.4.3 Complications
The main complication of peritoneal dialysis is peritonitis, signs of which include cloudy fluid in the
drainage bag, abdominal pain, and fever. Cell counts and cultures of the peritoneal fluid are used
Clamp
Disposable tubing
Clamp
To drain bag
FIGURE 6.4 Peritoneal catheter. (Courtesy of the National Institute of Diabetes and Digestive and Kidney
Diseases, National Institutes of Health.)
86 Nutrition Therapy for Chronic Kidney Disease
to confirm peritonitis while empiric antibiotics are started. The preferred method for administering
antibiotics is intraperitoneal. Episodes of peritonitis may have detrimental effects on the functional-
ity of the peritoneal membrane (Jovanovi et al., 1999). After multiple episodes of peritonitis, the
peritoneum may lose the ability to serve as an effective membrane for dialysis. Patients must also be
monitored for signs of exit-site infection of the peritoneal catheter.
6.4.5 Nutrition
Nutrition is very important for peritoneal dialysis patients. Poor nutrition has been shown to increase
the relative risk of death, hospitalization, and technique failure in peritoneal dialysis patients
(Canada-USA, 1996). There is significant protein loss associated with peritoneal dialysis. The loss
of protein is thought to occur through large pores in the peritoneal membrane from the capillaries
that supply the membranes. Peritoneal dialysis patients with high peritoneal membrane transport
characteristics have more protein losses than patients with low peritoneal membrane transport char-
acteristics (Daugirdas et al., 2006). Protein losses increase during episodes of peritonitis. During
dwells, peritoneal dialysis patients have large volumes of dialysate in their peritoneal cavity. This
may result in a feeling of fullness that may suppress the desire to eat, negatively impacting the
patients nutritional status. The dialysate fluids are typically dextrose-containing fluids. The glu-
cose in the fluid is systemically absorbed and can impact blood glucose levels and affect appetite
(Hylander et al., 1992). Dextrose-containing fluids can negatively impact diabetic control in diabetic
patients. Icodextrin is a newer dialysate solution that has less systemic absorption of glucose and
allows sustained ultrafiltration as it maintains the osmotic gradient for a longer time (Rodriguez-
Carmona et al., 2007).
6.5 HEMODIALYSIS
In hemodialysis, blood passes through a dialyzer to achieve clearance of toxins and removal of
fluid. In-center hemodialysis occurs three times per week, and each treatment typically lasts 34 h
(Figures 6.5 and 6.6). A vascular access or shunt is required, as is discussed later. Blood drawn
out of the patient through an arterial needle using a blood pump runs on a continuous circuit
through the dialyzer and is then returned to the patient via a venous needle. The dialyzer is a tube
with two compartments separated by a semipermeable membrane. The blood travels through hol-
low fibers on one side of the dialyzers semipermeable membrane; the dialysate runs through the
other compartment in the opposite direction on the other side of the dialyzers semipermeable mem-
brane (Figure 6.7). Dialysate consists of purified water mixed with electrolyte solutions of various
concentrations. Solutes are cleared as the blood and dialysate pass in a countercurrent flow. The
solutes are cleared from the patient by the process of diffusion from areas of high concentration to
areas of lowconcentration. The properties of the dialysis membrane, the blood flow rate (typically
300500m L/min), and dialyzer flow rate (typically 500800 mL/min), all help to determine the
Current Techniques for Dialysis 87
Dialyzer inflow
pressure monitor
Venous
pressure monitor
Heparin pump
(to prevent
clotting)
Dialyzer Air trap and
air detector
Air detector
clamp
Clean blood
returned to
Arterial body
pressure monitor
Blood removed
for cleansing
Blood pump
FIGURE 6.6 Mechanics of hemodialysis. (Courtesy of the National Institute of Diabetes and Digestive and
Kidney Diseases, National Institutes of Health.)
efficiency of clearance of various solutes. The length of dialysis is adjusted as needed to ensure
adequate clearance. Ultrafiltration refers to the removal of fluid using pressure applied across the
membrane. Convective transport occurs as solutes move with the ultrafiltrate. Anticoagulation is
often used during hemodialysis to prevent clotting of blood in the tubing or as the blood passes
through the dialyzer (Figure 6.8).
In some instances, patients may receive hemodialysis at home. The patients home environment,
social support, compliance, and ability to be properly trained to perform dialysis and handle problems
are all assessed before this modality is offered. Home hemodialysis may be done three times a week,
on a daily basis, or on any schedule in between (Figure 6.9). Intensive dialysis involves increasing
the frequency of dialysis or the duration of dialysis to improve clearance or volume removal. Dialysis
88 Nutrition Therapy for Chronic Kidney Disease
Blood inlet
Header
Tube sheet
Solution
outlet
Fibers
Jacket
Solution
inlet
Blood outlet
FIGURE 6.7 The dialysis membrane. (Courtesy of the National Institute of Diabetes and Digestive and
Kidney Diseases, National Institutes of Health.)
FIGURE 6.8 Typical hemodialysis machine. (From Andre Malov/Dreamstime.com, Dreamstime USA
Headquarters, Brentwood, TN. With permission.)
may also be done while the patient sleeps; this is called nocturnal hemodialysis. Some centers offer
in-center nocturnal hemodialysis, or it may be done in the home. Nocturnal hemodialysis typically
has a longer duration and lower blood flow than standard hemodialysis. It is a good option for patients
who wish to continue to work. Longer and more frequent dialysis sessions are more physiologic than
the typical thrice-weekly short sessions of hemodialysis. Studies have shown improvements in hyper-
tension, hyperphosphatemia, and left ventricular function with more intensive hemodialysis (Chan
etal., 2002, 2005; Seabra et al., 2008; Toussaint and Boddington, 2006). Patients receiving nocturnal
Current Techniques for Dialysis 89
FIGURE 6.9 Patient on home hemodialysis. (Courtesy of the National Institute of Diabetes and Digestive
and Kidney Diseases, National Institutes of Health.)
hemodialysis may have improved clearance of fluid, phosphorous, and electrolytes such as potassium
allowing for liberalization of the patients diet. The dietary restrictions imposed during hemodialysis
are a frequent source of complaints from dialysis patients. However, a recent study did not demon-
strate any significant improvement in measures of quality of life with nocturnal hemodialysis as
compared to patients on conventional hemodialysis (Manns and Walsh, 2009).
Serious complications of hemodialysis include hypotension, bleeding, infection, and vascular access
issues. Hypotension may occur due to rapid fluid or electrolyte shifts during hemodialysis. Hypotension
on hemodialysis is typically treated by decreasing the ultrafiltration rate or giving a fluid bolus. Blood
pressure (BP) medications often need to be adjusted after initiation of hemodialysis to avoid intradia-
lytic hypotension. There is a risk of bleeding and blood loss due to the cannulation of large blood ves-
sels, the use of a blood pump to achieve high blood flow rates, and the use of anticoagulation to prevent
clotting. Careful monitoring of access sites and monitoring for venous needle dislodgement can help
prevent bleeding complications. Sterile technique should always be used to access vascular access sites,
and all reusable equipment must be carefully sterilized. To reduce complications, patients must also be
educated about how to care for their vascular access or catheters. Serious complications including death
may occur if proper care is not taken to avoid contamination and to ensure proper balance and purifica-
tion by the water delivery systems used in hemodialysis. Less serious, but perhaps the most common
complication, is cramping during hemodialysis. Cramping is typically related to fluid and electrolyte
shifts and can be improved by limiting weight gains and avoiding high sodium foods. The temperature
of dialysate must also be closely monitored. Dialysate above physiologic temperatures may result in
hemolysis and patient death. Cooler dialysate temperatures have been shown to improve hemodynamic
measures in otherwise unstable patients, but use of this can be limited by patient intolerance.
Labs are monitored and patients are assessed, typically on a monthly basis for hemodialysis
patients. The nephrologist provides oversight for the management of lipids, hypertension, electro-
lytes, anemia, iron deficiency, renal osteodystrophy, and clearance. Adequacy of dialysis is mea-
sured and reported as Kt/V, where K is the coefficient of the dialyzer being used, t is the time on
hemodialysis, and V is the volume of distribution of urea of the dialyzed patient. Typically, larger
patients require more time on hemodialysis to achieve adequate clearance. There is debate about
whether there is a better way to scale dialysis dose, such as correcting for metabolic rate, and
90 Nutrition Therapy for Chronic Kidney Disease
whether the current Kt/V gives accurate information for women (Baslie and Vernaglione, 2010;
Morton and Singer, 2007; Spalding, 2008). However, for now, Kt/V remains the accepted standard-
ized measure of adequacy of dialysis.
25% in diabetics (National Kidney Foundation, 2000). Therefore, there has been significant inter-
est in exploring different aspects that may improve patient outcomes. The vast majority of data has
involved comparisons between peritoneal and in-center hemodialysis as these are the two primary
dialysis modalities. The results have been controversial. Studies that attempted to correct for age
and comorbidities have shown conflicting results. One prospective study found that mortality risk
was the same during the first year for both hemodialysis and peritoneal dialysis patients, but dur-
ing the second year, mortality was higher for peritoneal dialysis patients (Jarr et al., 2005). One
study found that the survival was less dependent on modality and more influenced by the Kt/V or
the adequacy of dialysis (Keshaviah and Collins, 2002). This finding supported earlier studies that
indicated that of all the factors impacting mortality, the most important was dose of dialysis (Collins
and Ma, 1994). An Italian study showed similar findings indicating that the most important factors
were age and predialysis comorbidity as well as predialysis nutritional status and adequacy of dialy-
sis (Maiorca et al., 1996). A large Canadian study found that the survival advantage of peritoneal
dialysis was related to differences in comorbidities at the time of initiation of dialysis. Overall, this
study did not determine that there was a difference in survival rates between hemodialysis and peri-
toneal dialysis patients (Murphy and Foley, 2000).
One study compared the hospitalization rates between patients on the home modalities of daily
hemodialysis as compared to peritoneal dialysis. Patients treated with daily hemodialysis had lower
rate of hospitalization and shorter length of stay than patients on peritoneal dialysis (Kumar et al.,
2008).
Multiple studies have compared intermittent hemodialysis (IHD) to CRRT for acute kidney-
injury patients who require RRT. One study found that the modality of RRT did not affect the
outcomes of ICU patients with acute kidney injury (Lins etal., 2009). Another study found similar
outcomes, but significantly increased ICU-related costs for patients treated with CRRT rather than
IHD (Rauf et al., 2008). The lack of significant improvement in outcomes with CRRT has been
supported by meta-analyses (Ghahrmani and Shadrou, 2008). However, according to recently pub-
lished data, the proportion of patients who receive CRRT has increased over time (Afshinnia and
Straight, 2009). One systematic review in 2008 found that early initiation of RRT in acute renal
failure may be associated with improved survival (Seabra et al., 2008).
6.9 SUMMARY
Deciding to initiate dialysis is a complex process to which patients are often initially resistant. Proper
patient education may improve patient outcomes and will improve a patients ability to participate in
the decision making regarding this difficult process. Early nephrology referral and proper dialysis
planning will improve outcomes for patients. The main chronic dialysis modalities are hemodialysis
and peritoneal dialysis. Individual patient characteristics and social issues must be considered when
determining the best modality for a given patient. Alternative dialysis therapies are available, both
in the chronic and acute setting, each of which has advantages and disadvantages.
REFERENCES
Afshinnia, F., Straight, A. 2009. Trends in dialysis modality for individuals with acute kidney injury. Renal
Failure 31(8):647654.
Baslie, C., Vernaglione, L. 2010. Comparison of alternative methods for scaling dialysis dose. Nephrol Dial
Transplant. 25(4):12321239.
Blake, P. 2009. Proliferation of hemodialysis units and declining peritoneal dialysis use: An international trend.
Am J Kidney Dis. 54(2):194196.
Boen, S.T. 1961. Kinetics of peritoneal dialysis. Medicine 40:243.
Canada-USA Peritoneal Dialysis Study Group. 1996. Adequacy of dialysis and nutrition in continuous perito-
neal dialysis: Associate with clinical outcomes. J Am Soc Nephrol. 7:198.
92 Nutrition Therapy for Chronic Kidney Disease
Chan, C., Flores, J., Miller, J., et al. 2002. Improvement in ejection fraction by nocturnal hemodialysis in end
stage renal failure patients with coexisting heart failure. Nephrol Dial Transplant. 17:15181521.
Chan, C., Jain, V., Picton, P. 2005. Nocturnal hemodialysis increases arterial baroreflex sensitivity and compli-
ance and normalizes blood pressure of hypertensive patients with end-stage renal disease. Kidney Int.
68:338344.
Collins, A., Ma, J. 1994. Urea index and other predictors of hemodialysis patient survival. Am J Kidney Dis.
23 (2):272282.
Cooper, B., Branley, P., Bulfone, L., et al. 2010. A randomized, controlled trial of early versus late initiation of
dialysis for the IDEAL study. N Engl J Med. 363:609619.
Daugirdas, J., Blake, P., Ing, T. 2006. Handbook of Dialysis, 4th edn. Lippincott Williams & Williams.
Ghahrmani, N., Shadrou, S. 2008. A systematic review of continuous renal replacement therapy and intermit-
tent hemodialysis in management of patients with acute renal failure. Nephrology 13(7):570578.
Hylander, B., Barkeling, B., Rossner, S. 1992. Eating behavior in continuous ambulatory peritoneal dialysis
and hemodialysis. Am J Kidney Dis. 20:592.
Jarr, B., Coresh, J., Plantinga, L. 2005. Comparing the risk for death with peritoneal dialysis and hemodialysis
in a national cohort of patients with chronic kidney disease. Ann Intern Med. 143:174.
Jovanovi, D., Nesi, V., Dimitrijevic, Z. 1999. The effect of the number of peritonitis episodes on peritoneal
membrane function. Srp Arh Celok Lek. 127(12):2831.
Keshaviah, P., Collins, A. 2002. Survival comparison between hemodialysis and peritoneal dialysis based on
matched doses of delivered therapy. Am Soc Nephrol. 13(Suppl):S48S52.
Kessler, M., Frimat, L., Panescu, V., et al. 2003. Impact of nephrology referral on early and midterm outcomes
in ESRD: EPidmiologie de lInsuffisance REnale chronique terminale en Lorraine (EPIREL): Results
of a 2-year, prospective, community-based study. Am J Kidney Dis. 42(3):474485.
Kumar, V., Ledezma, M., Idroos, M. 2008. Hospitalization rates in daily home hemodialysis versus peritoneal
dialysis patients in the United States. Am J Kidney Dis. 52(4):737744.
Lins, R., Eiseviers, M., Van der Niepen, P. 2009. Intermittent versus continuous renal replacement therapy of
acute kidney injury patients admitted to the intensive care unit: Results of a randomized clinical trial.
Nephrol Dial Transplant. 24(2):512518.
Maiorca, R., Cancarini, G., Brunori, G. 1996. Comparison of long-term survival between hemodialysis and
peritoneal dialysis. Adv Perit Dial. 12:7988.
Manns, B., Walsh, M. 2009. Nocturnal hemodialysis does not improve overall measures of quality of life com-
pared to conventional hemodialysis. Kidney Int. 75(5):542549.
Morton, A., Singer, M. 2007. The problem with Kt/V: Dialysis dose should be normalized to metabolic rate not
volume. Semin Dial. 20(1):1215.
Murphy, S., Foley, R. 2000. Comparative mortality of hemodialysis and peritoneal dialysis in Canada. Kidney
Int. 57:17201726.
National Kidney Foundation. 2006. K/DOQI Clinical Practice Guidelines for Vascular Access. Guideline 8,
Timing of Access Placement. Am J Kidney Dis. 48:S176S247, Suppl 1.
National Kidney Foundation. 2007. K/DOQI Clinical Practice Guidelines for Chronic Kidney Disease
Evaluation, Classification, and Stratification. Part 5. Definition and Classification of Stages of Chronic
Kidney Disease. Am J Kidney Dis. 49(2):S12S154, Suppl 2.
Rauf, A., Long, K., Gajic, O., et al. 2008. Intermittent hemodialysis versus continuous renal replacement ther-
apy for acute renal failure in the intensive care unit: An observational outcomes analysis. J Intensive Care
Med. 23(3):195203.
Rodriguez-Carmona, A., Perez Fontan, M., Garcia Lopez, E., et al. 2007. Use of icodextrin during nocturnal
automated peritoneal dialysis allows sustained ultrafiltration while reducing the peritoneal glucose load:
A randomized crossover study. Periton Dialysis Int. 27(3):260266.
Seabra, V., Balk, E., Liangos, O., et al. 2008. Timing of renal replacement therapy initiation in acute renal fail-
ure: A meta-analysis. Am J Kidney Dis. 52(2):272284.
Spalding, E. 2008. Kt/V underestimates the hemodialysis dose in women and small men. Kidney Int.
74(3):348355.
Toussaint, N., Boddington, J. 2006. Calcium phosphate metabolism and bone mineral density with nocturnal
hemodialysis. Hemodial Int. 10:280286.
United States Renal Data System. 2010. Excerpts from the USRDS 2009 annual data report: Atlas of end-stage
renal disease in the United States. Am J Kidney Dis. 1(Suppl 1):S1.
7 Screening and Assessment
Nutrition Care Process
Claire Moise
WJB Dorn VA Medical Center
Lynn K. Thomas
University of South Carolina School of Medicine
CONTENTS
7.1 Kidney Disease: Past and PresentIntroduction.................................................................... 93
7.2 Nutrition Screening.................................................................................................................94
7.3 Nutrition Assessment...............................................................................................................94
7.3.1 Subjective Global Assessment.....................................................................................94
7.3.2 Medical History...........................................................................................................96
7.3.3 The Effect of Comorbidities........................................................................................97
7.3.4 Medications and DrugNutrient Interactions..............................................................97
7.3.5 Psychosocial History...................................................................................................97
7.3.6 Diet History.................................................................................................................97
7.3.7 Physical Examination.................................................................................................. 98
7.3.8 Height, Weight, and Other Anthropometric Measures................................................ 98
7.3.9 Nutrient Calculations................................................................................................. 100
7.3.10 Laboratory Data......................................................................................................... 104
7.4 Monitoring............................................................................................................................. 104
7.5 Summary............................................................................................................................... 106
References....................................................................................................................................... 106
93
94 Nutrition Therapy for Chronic Kidney Disease
Ideally, a renal dietitian will complete the nutrition assessment, especially in the later stages
of CKD. When a renal dietitian is not available, an experienced clinical dietitian is also capable
of completing an inclusive review of a patients nutrition status. The use of an electronic medical
record allows for ready access to all the information provided by many team members in a physician
practice setting, a hospital setting, or a dialysis clinic. A thorough search of the entries will ensure
a complete nutrition assessment.
The American Dietetic Association (2008) supports the use of standardized terminology for the
NCP. The NCP includes four steps: assessment, diagnosis, intervention, and monitoring/evaluation.
In this chapter, the discussion on NCP is limited to assessment.
Typical criteria used for screening include history of weight loss (% of usual body weight, body
mass index [BMI], etc.), loss of appetite, malnourished appearance, laboratory indices, and effect of
current medical problems. Several inclusive screening instruments such as the Malnutrition Universal
Screening Tool (Weekes et al., 2004), the Mini Nutritional AssessmentShort Form (Kaiser et al.,
2009), and the Short Nutritional Assessment Questionnaire (Kruizenga et al., 2005) are available.
They are useful for screening patients in the early stages of CKD in which the focus is on control of
comorbidities (Figure 7.1). An appropriate follow-up time frame should be in place for rescreening.
Screening
A Has food intake declined over the past 3 months due to loss of appetite, digestive problems, chewing or
swallowing difficulties?
0 = severe decrease in food intake
1 = moderate decrease in food intake
2 = no decrease in food intake
B Weight loss during the last 3 months
0 = weight loss greater than 3 kg (6.6 lbs)
1 = does not know
2 = weight loss between 1 and 3 kg (2.2 and 6.6 lbs)
3 = no weight loss
C Mobility
0 = bed or chair bound
1 = able to get out of bed / chair but does not go out
2 = goes out
D Has suffered psychological stress or acute disease in the past 3 months?
0 = yes 2 = no
E Neuropsychological problems
0 = severe dementia or depression
1 = mild dementia
2 = no psychological problems
2
F1 Body Mass Index (BMI) (weight in kg) / (height in m )
0 = BMI less than 19
1 = BMI 19 to less than 21
2 = BMI 21 to less than 23
3 = BMI 23 or greater
Screening score
(max. 14 points)
Ref.
Vellas B, Villars H, Abellan G, et al. Overview of the MNA - Its History and Challenges. J Nutr Health Aging 2006;10:456-465.
Rubenstein LZ, Harker JO, Salva A, Guigoz Y, Vellas B. Screening for Undernutrition in Geriatric Practice: Developing the Short-Form Mini
Nutritional Assessment (MNA-SF). J. Geront 2001;56A: M366377.
Guigoz Y. The Mini-Nutritional Assessment (MNA ) Review of the Literature - What does it tell us? J Nutr Health Aging 2006; 10:466487.
Kaiser MJ, Bauer JM, Ramsch C, et al. Validation of the Mini Nutritional Assessment Short-Form (MNA -SF): A practical tool for identification
of nutritional status. J Nutr Health Aging 2009; 13:782788.
FIGURE 7.1 Mini Nutrition AssessmentShort Form. (From Nestl S.A., Mini nutrition assessment,
N67200 12/99 10M, 1994, Revision 2009. With permission.)
96 Nutrition Therapy for Chronic Kidney Disease
tool. The SGA uses these core categories: weight status, dietary intake, gastrointestinal symptoms,
functional status, metabolic stress, and physical examination (Detsky et al., 1987; Figure 7.2).
FIGURE 7.2 Subjective Global Assessment. (Reproduced from Detsky, A. et al., J. Parenteral Enteral Nutr.,
11, 9, 1987. With permission of American Society for Parenteral and Enteral Nutrition.)
Nutrition Care Process 97
might be documented in the medication review. Questions for the diet history include the follow-
ing: When was the last complete meal? Are there any chewing and swallowing difficulties?
Is there a problem with dryness, pain, or sores in the mouth? Are teeth/dentures in good con-
dition? Questions about appetite are important. Information about any special diets needs to be
documented. Details regarding meal patterns and whether the patient has anything else to tell about
diets or foods should be documented.
Although many patients will readily give an accurate account of a days food intake, it would be
helpful to quantify intake over time. Recording the intake of certain items over time is also impor-
tant. A food frequency questionnaire or 37-day food diaries can be beneficial when looking for
deficiencies or overages. Food models and food pictures are ways patients can show meal patterns
and portion amounts. Once the data are obtained, the dietitian can then do the analysis either manu-
ally or using a computerized analysis program. The U.S. Department of Agriculture offers a free
analysis program on http://www.choosemyplate.gov and an accessible nutrient database on http://
www.nal.usda.gov/fnic/foodcomp/search (USDA, 2011; Williams, 2003).
TABLE 7.1
Physical Examination Findings and Possible Deficiencies
Findings Deficiency Excess
Eyes Xerophthalmia Vitamin A
Blurred vision Vitamin A
Pale conjunctiva Iron
Mouth Cracking teeth Vitamin A
Decreased saliva Riboflavin, folate
Glossitis Cobalamin
Cheilosis Ascorbic acid
Bleeding gums Niacin
Atrophic papillae
Hair Alopecia Protein-calorie, biotin
Brittle, pluckable Zinc
Color change Vitamin A
Dryness
Nails Transverse ridging Protein
Koilonychia Iron
Extremities Osteomalacia Vitamin D
Muscle twitching Thiamine
Muscle weakness Riboflavin
Skin Dry, scaly, keratinization Vitamin A
Dermatitis Riboflavin
Cheilosis Ascorbic acid
Ecchymosis
Petchiae
Flushing and yellow pigmentation of Niacin
palms with normal white sclera Excess beta carotene
Systems Kidney stones Vitamin D
Increased prothrombin time Vitamin K
Enlarged heart Thiamine
Beriberi Niacin
Pellagra Cobalamin, Thiamine
Neurological Vitamin A
Decrease immune function
Source: Food and Nutrition Board, Institute of Medicine, Dietary Reference Intakes, National Academies
Press, Washington, DC, 2006. With permission; Food and Nutrition Board, Institute of Medicine, .
Dietary Reference Intake: Water, 2011. Online: http://iom.edu/Activities/Nutrition/
SummaryDRIs/~/media/Files/Activity%20Files/Nutrition/DRIs/DRI_Electrolytes_Water.ashx
(accessed 30 May 2011). With permission.
Triceps skin fold (TSF) thickness and arm muscle area (AMA) measurements are useful in pre-
dicting body composition. TSF is an index of body fat stores, and AMA represents muscle protein.
Both measurements are taken using the midpoint of the patients arm (Figure 7.5). A caliper is used
for measuring the TSF, and a measuring tape is used for determining the AMA. Further calculations
are required for deriving the AMA: mid-arm circumference - (TSF 0.314) = mid-arm muscle
circumference (MAMC). AMA = (MAMC) 2/12.56. Tables of reference data are used to determine
percentile ranks (Table 7.6). In the elderly, change in body composition over time can decrease the
reliability of these assessments (Frisancho, 1989).
100 Nutrition Therapy for Chronic Kidney Disease
TABLE 7.2
Determination of Height
Method Comments
Arm span Fully extend the upper extremities including hands; hold parallel to Measurement will be within
the ground; measure the distance between the tip of one middle 10% of adult height
finger to the tip of the opposite middle finger
Knee height Equation: Men = (2.02 knee height in cm) (0.04 age) + 64.19 Used for those with curvature of
Women = (1.83 knee height in cm) (0.24 age) + 84.88 the spine, who are bedridden or
Convert to inches by dividing the result by 2.54 who are using wheel chair
(a) (b)
FIGURE 7.3 Knee height calculations. (Adapted from Hwang, C., et al., Epidemiol. Health, 31, 16, 2009.)
Body position for the measurement of knee height in clinical validation group: (a) healthy elderly group and
(b) mobility-impaired group. In both groups, knee height was measured using a flexible tape, whereas the knee
and ankle joints were flexed at 90. (a) It was measured in the sitting position with a tape attached to the wall
and was defined as the distance between the floor and suprapatellar point. This method is identical to the one
used in Size Korea 2004. (b) In recumbent position, the measured distance is between landing point and
suprapatellar point from lateral side.
TABLE 7.3
Frame Size from Elbow Breadth in Centimeters
Age (years) Small Frame Medium Frame Large Frame
Males
2534 6.7 >6.7 <7.9 7.9
3544 6.7 >6.7 <8.0 8.0
4574 6.7 >6.7 <8.1 8.1
Females
2534 5.7 >5.7 <6.8 6.8
3544 5.7 >5.7 <7.1 7.1
4554 5.7 >5.7 <7.2 7.2
5564 5.8 >5.8 <7.2 7.2
8%
2.7%
5% 50%
1.6%
0.7%
10.1%
16%
4.4%
1.5%
FIGURE 7.4 Adjustments for amputees. (Reprinted from Journal of the American Dietetic Association, 95,
Osterkamp, L., Current perspective on assessment of human body proportions of relevance to amputees, 217,
1995, with permission from Elsevier.)
activity-related energy expenditure is as much as 53% lower on days on which the patient is on dialy-
sis and 28% lower on days on which the patient is not on dialysis (Baria et al., 2011).
Most calculations for daily energy expenditure will equate to 3035 cal/kg for patients with
CKD. Besides the formulas for energy estimation, formulas for estimation of adjusted weight and
dry weight are available.
The National Kidney Foundation (NFK) KDOQI Clinical practice guidelines recommends a
range of 3050 cal/kg actual or dry weight categorized based on the stage of CKD and on varia-
tions for age, weight, stress, etc. (Masud and Mitch, 2010; NKF, 2000). Other equations such as the
HarrisBenedict formula with adjustments for stress can be used for calculating the total energy
expenditure (Harris and Benedict, 1919).
Men: Basal energy expenditure (BEE) = 66.42 + 13.75 (weight) + 5.0 (height) 6.8 (age).
Women: BEE = 655.1 + 9.65 (weight) + 1.85 (height) 4.68 (age)
102
TABLE 7.4
BMI Table
Normal Overweight Obese
19 20 21 22 23 24 25 26 27 28 29 30 35 40
Height (in.) Weight (lb)
58 91 96 100 105 110 115 119 124 129 134 138 143 167 191
59 94 99 104 109 114 119 124 128 133 138 143 148 173 198
60 97 102 107 112 118 123 128 133 138 143 148 153 179 204
61 100 106 111 116 122 127 132 137 143 148 153 158 185 211
62 104 109 115 120 126 131 136 142 147 153 158 164 191 218
63 107 113 118 124 130 135 141 146 152 158 163 169 197 225
64 110 116 122 128 134 140 145 151 157 163 169 174 204 232
65 114 120 126 132 138 144 150 156 162 168 174 180 210 240
Source: Parameters for normal based on Federal Obesity Clinical Guidelines, National Heart Lung and Blood Institute, 2000.
Nutrition Care Process 103
TABLE 7.5
Hamwi Method for DBW or IBW
Men: 106 pounds for first 5 feet and 6 pounds for every additional inch
Women: 100 pounds for first 5 feet and 5 pounds for every additional inch
Add or subtract 10% to accommodate large or small frame size
Subtract 5%10% from DBW for paraplegia
Subtract 10%15% from DBW for quadriplegia
FIGURE 7.5 TSF measurement illustration. (From Shaun Riffle, USC School of Medicine, Columbia, SC.
With permission.)
In the aforementioned formulas, weight, height, and age are expressed in kilograms, centimeters,
and years, respectively.
Total energy expenditure (TEE) = BEE stress factor. The stress factor varies from 0.85 in sim-
ple starvation to 1.4 in sepsis. Most patients with CKD fall in the 1.01.2 range (Barak et al., 2002).
The IretonJones energy equation for spontaneously breathing patients is also widely used:
Estimated energy expenditure (EEE) calories per day = 629 11 (age/years) + 25 (weight/kg)
609 (presence of obesity factor)
Presence of obesity factor = 30% > IBW (absent = 0, present = 1) (IretonJones and Jones, 1998).
Adjusted-weight formulas are recommended when a patient is above 125% of DBW. This recommen-
dation is based on the premise that in an obese patient not all fat is metabolically active. The usual
adjustment is as follows: DBW + [(actual BW IBW 0.25)] (Frankenfield et al., 2003). If nutrient
recommendations are based on actual body weight, then an overestimation might occur (Frisancho,
1984). Upon review, the MifflinSt. Jeor formula has been found to have one of the smallest overes-
timation errors (Frankenfield et al., 2005). The formula is as follows (Mifflin et al., 1990):
Here, RMR is the resting metabolic rate in calories per day. Weight is expressed in kilograms and
height in centimeters.
104 Nutrition Therapy for Chronic Kidney Disease
TABLE 7.6
TSF and AMA: Abbreviated Reference Table
TSF Adult Male (1865 Years; Measured
in mm) Percentile (%) AMAC Adult Male (1865 Years; Measured in cm)
4.05.0 10 37.338.7
10.011.5 50 49.452.1
17.520.0 85 61.864.8
TSF Adult Female (1865 Years; AMAC Adult Female (1865 Years; Measured in cm)
Measured in mm)
11.016.0 10 21.524.5
12.017.5 50 28.334.5
18.526.0 85 36.445.6
Source: Frisancho, A. Anthropometric Standards for the Assessment of Growth and Nutrition Status, University of Michigan
Press, Ann Arbor, MI, 1989.
Fluid management is dependent on the severity of acute kidney failure or on the stage of CKD.
Goals include balanced hydration and normalized electrolytes. Insensible losses, input/output mea-
sures, and any fevers, sweating, or gastric/kidney fluid losses secondary to the current medical prob-
lem should all be considered when establishing a daily fluid limit for the patient (Whitmire, 1998).
The HollidaySegar equation (1957) is used to estimate general fluid needs:
For weight >20 kg, use 1500 mL + 20 mL/kg for each kg >20.
The Food and Nutrition Board, Institute of Medicine (2011) sets the dietary reference intake of
all fluids as 3.7 L/day for men and 2.7 L/day for women.
Daily protein, vitamin, and mineral requirements vary based on the stage of CKD. Each of these
elements is discussed in later chapters for both pediatric and adult indications.
7.4 MONITORING
Once the assessment is complete, it is important to monitor the tolerance and the benefits of
the recommendations. A timely follow-up should always be scheduled to make certain that any
changes in the nutrition status are documented and that adjustments to the intervention are made
quickly.
Nutrition Care Process 105
TABLE 7.7
Common Laboratory Data
Kidney
Target Value (Varies Disease
Blood Test with Lab) Target Comments
Albumin (g/L) 3555 (depends on 3550 High in dehydration. Low in fluid overload and
assay bromcresol green infection.
[BCG] vs. bromcresol
purple [BCP])
Alkaline phosphatase (U/L) 42128 42128 Monitored for suspected bone disease.
Blood urea nitrogen (mmol/L) 3.67.1 14.421.4 Varies with various stages of chronic kidney
disease (CKD) and dialysis adequacy
Calcium (Ca++) (mmol/L) 2.32.8 2.32.8 Low with insufficient vitamin D; high with
excess. With low albumin, use corrected Ca++
formula or obtain ionized Ca++ value.
C-reactive protein (mg/dL) <0.8 <0.8 A sign of inflammation. If high, look for the
cause: infection, malignant disease, autoimmune
Creatinine (mol/L) Male: 53106 176.81326 High in catabolism
Female: 4497 Low in wasting
Ferritin (pmol/L) Male: 12300 CKD or PD: High in inflammation
Female: 10150 >224.7 Low in iron deficiency
HD: >449.4
Glucose (mmol/L) 3.95.8 3.95.8 High: diabetes mellitus
Low: Malnutrition
Note: Clinic labs values are usually nonfasting
values
Hemoglobin (Hgb) (mmol/L) Male: 8.71.2 CMS targets: Low: Fluid overload, anemia, CKD, blood loss
Female: 7.49.9 6.27.44
Carbon dioxide (mmol/L) 2331 2331 High: Metabolic acidosis
Low: Metabolic alkalosis
Cholesterol (mmol/L) <5.2 <5.2 Low: Acute infection, malnutrition
High-density lipoprotein >1.5 >1.5
cholesterol (HDL-C) <2.6 <2.6
Low-density lipoprotein <1.7 <1.7
cholesterol (LDL-C)
Triglycerides (mmol/L)
Iron (mmol/L) 1331 1331
Magnesium (mmol/L) 0.61.0 0.61.0 Low: Malnutrition, diarrhea, alcohol abuse
Phosphorus (mmol/L) 0.971.45 0.971.45 High: CKD, vitamin D intoxication, inadequate
binder
Low: Vitamin D deficiency, malabsorption,
refeeding syndrome, osteomalacia
Plasma intact parathyroid 1065 150300 High: Hyperparathyroidism, vitamin D deficiency
hormone (PTH; pg/mL) Low: Hypoparathyroidism, vitamin D intoxication
Potassium (mmol/L) 3.55.0 3.56.0 High: CKD, tissue trauma, hyperglycemia
Low: Diuretic therapy, ETOH abuse, vomiting,
and diarrhea
Pre-albumin/transthyretin 150360 30 Low: Inflammation, malnutrition
(mg/L)
Sodium (mmol/L) 136145 136145 High: Dehydration
Low: Overhydration, starvation, hyperglycemia
Transferrin saturation (%) 1648 2050 High: Iron overload
Low: Malnutrition
106 Nutrition Therapy for Chronic Kidney Disease
TABLE 7.8
Serum Hepatic Transport Proteins
Protein Change
Albumin (Half life = 1420 days) Increases with intravascular volume Decreases with inflammation, liver
Prealbumin (Half life = 2 days) depletion and use of steroids failure, pregnancy, volume overload,
protein wasting diseases, exudates,
and severe zinc deficiency
Prealbumin (Half life = 2 days) Increases with intravascular volume Decreases with inflammation,
depletion, use of steroids, and malignancies, protein wasting
some cases of nephritic syndrome diseases, and severe zinc deficiency
Retinol-binding protein (Half life = 12 h) Increases in renal failure Decreases in uncomplicated protein
calorie malnutrition and low vitamin A
Transferrin (Half life = 8 days) Increases with iron deficiency, Decreases with liver disease, chronic
pregnancy, and alcoholism disease, inflammation, malignancies,
and collagen vascular diseases
C-reactive protein (CRP) and highly
sensitive CRP are best used to measure
the presence of inflammation
7.5 SUMMARY
The NCP starts with screening and expands into a thorough nutrition assessment when necessary.
The paramount goals of both screening and assessment are to ensure that the resulting nutrition
treatment is optimal for the patient. There are many parts to the nutrition assessment process, and
no part is the best. Experience, clinical recommendations from the American Dietetic Association,
the Council on Renal Nutrition, and the KDOQI guidelines, and the literature on evidence-based
medicine will help the practitioner to decide on the NCP for a patient.
REFERENCES
American Dietetic Association Evidence Library. 2011. Nutrition care process: Nutrition screening. Online:
www.adaevidencelibrary.com (accessed May 2011).
American Dietetic Association Position Paper. 2009. Nutrient supplementation. J Am Dental Assoc.
109:20732085.
American Dietetic Association Writing Group for the Nutrition Care Process/ Standardized Language
Committee. 2008. Nutrition care process and model part I: The 2008 update. J Am Dental Assoc.
108:11131117.
Barak, N., Wall-Alonso, E., Sitrin, M. 2002. Evaluations of stress factors and body weight adjustments currently
used to estimate energy expenditure in hospitalized patients. J Parenteral Enteral Nutr. 26:231238.
Baria, F., Kamimura, M., Avesani, C., Lindholm, B., Stenvinkel, P., Draibe, S., Cuppari, L. 2011. Activity-
related energy expenditure of patients undergoing hemodialysis. J Renal Nutr. 21:226234.
Blackburn, G. 1977. Nutrition and metabolic assessment of the hospitalized patient. J Parenteral Enteral Nutr.
1:1122.
Chumlea, W., Guo, S., Wholihan, K., Cockram, D., Kuczmarski, R., Johnson, C. 1998. Stature prediction equa-
tions using knee height for elderly Americans from NHANES III. J Am Diet Assoc. 98:137142.
Cresci, G. 2004. Patient history. In Charney, P., Malone, A., eds. ADA Pocket Guide to Nutrition Assessment.
Chicago, IL: American Dietetic Association.
Detsky, A., McLaughlin, J., Baker, J., Johnston, N., Whittaker, S., Mendelson, R., Jeejeebhoy, K. 1987. What is
subjective global assessment of nutrition status? J Parenteral Enteral Nutr. 11:813.
Federal Obesity Guidelines. 2000. National Heart Lung and Blood Institute. Online: http://www.nhlbi.nih.gov/
guidelines/obesity/prctgd_c.pdf (accessed 05 January 2012).
Nutrition Care Process 107
Food and Nutrition Board, Institute of Medicine. 2011. Dietary reference intake: Water. Online: http://iom.edu/
Activities/Nutrition/SummaryDRIs/~/media/Files/Activity%20Files/Nutrition/DRIs/DRI_Electrolytes_
Water.ashx (accessed 30 May 2011).
Food and Nutrition Board, Institute of Medicine. 2006. Dietary Reference Intakes. Washington, DC: National
Academies Press.
Frankenfield, D., Roth-Yousey, L., Compher, C. 2005. Comparison of predictive equations for resting
metabolic rate in healthy non-obese and obese adults: A systematic review. J Am Dental Assoc.
105(5):775789.
Frankenfield, D., Rowe, W., Smithe, J., Cooney, R. 2003. Validation of several established equations for resting
metabolic rate in obese and non-obese people. J Am Dental Assoc. 103:11521159.
Frisancho, A. 1984. New standards of weight and body composition by frame size and height for assessment of
nutrition status of adults and the elderly. Am J Clin Nutr. 40:808819.
Frisancho, A. 1989. Anthropometric Standards for the Assessment of Growth and Nutrition Status. Ann Arbor,
MI: University of Michigan Press.
Hamwi, G. 1964. Therapy: Changing dietary concepts. In: Danowski, T. ed., Diabetes Mellitus: Diagnosis and
Treatment, Volume 1. New York: American Diabetes Association, 7378.
Harris, J., Benedict, F. 1919. Biometric Studies of Basal Metabolism in Man. Washington, DC: Carnegie
Institution of Washington. Publication number 279, 227228.
Holliday, M., Segar, W. 1957. The maintenance need for water in parenteral fluid therapy. Pediatrics.
19:823832.
Hwang, C., Kim, K., Kang, H., Kang, D. 2009. Validity of stature-predicted equations using knee height for
elderly and mobility impaired persons in Koreans. Epidemiol Health 31:16.
Ireton-Jones, C., Jones, J. 1998. Should predictive equations or indirect calorimetry be used to design nutrition
support regimens? Nutr Clin Pract. 13:141143.
Kaiser, M., Bauer, J., Ramsch, C., Uter, W., Gudgoz, Y., Cederhome, T., Thomas, D., Anthony, P., Charlton, K.,
Maggio, M., Tsai, A., Grathwohl, D., Vellas, B., Sieber, C. 2009. Validation of the mini nutrition assess-
ment short form (MNA-SF): A practical tool for identification of nutrition status. J Nutr Health Aging.
13:782788.
Khan, F., Sachs, H., Pechet, L., Snyder, L. 2002. Guide to Diagnostic Testing. Philadelphia, PA: Lippincott,
Williams & Wilkins.
Kruizenga, H., Seidell, J., de Vet, H., Wierdsma, N., van Bokhorst-de van der Schueren, M. 2005. Development
and validations of a hospital screening tool for malnutrition: the short nutrition assessment questionnaire
(SNAQ). Clin Nutr. 24:7582.
Litchford, M. 2008. Assessment: Laboratory data. In Mahan, L., Escott-Stump, S. Krauses Food & Nutrition
Therapy. Philadelphia, PA: Saunders Elsevier, 411431.
Masud, T., Mitch, W. 2010. Requirements for protein, calories, and fat in the predialysis patient. In Mitch, W.,
Ikizler, T. Handbook of Nutrition and the Kidney, 6th edition. Philadelphia, PA: Lippincott Williams &
Wilkins, 92108.
Mifflin, M., St. Jeor, S., Hill, L., Scott, B., Daugherty, S., Koh, Y. 1990. A new predictive equation for resting
energy expenditure in healthy individuals. Am J Clin Nutr. 51:241247.
Mitchell, M. 1993. Comparison of determinants of frame size in older adults. JADA. 93(1):5357.
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). 2011. U.S. Department of
Health and Human Services. Weight and waist measurement tools. Online: http://win.niddk.nih.gov/
Publications/tools.htm#circumf (accessed 26 May 2011).
National Kidney Foundation (NKF). 2000. NKF KDOQI Clinical practice guidelines for nutrition in chronic
renal failure. Am J Kidney Disease. 35(6 Suppl 2):S1140.
Osterkamp, L. 1995. Current perspective on assessment of human body proportions of relevance to amputees.
J Am Diet Assoc. 95:215218.
Pronsky, Z., Crowe, J. 2008. Assessment: Food-drug interactions. In Mahan, L., Escott-Stump, S. Krauses
Food & Nutrition Therapy. Philadelphia, PA: Saunders Elsevier, 432453.
Russell, M., McAdams, M. 1998. Laboratory monitoring of nutrition status. In Matarese, L., Gottschlich, M.
Contemporary Nutrition Support Practice. Philadelphia, PA: Saunders, 4763.
Steiber, A., Leon, J., Secker, D., McCarthy, M., McCann, L., Serra, M., Sehgal, A., Kalantar-Zadeh, K. 2007.
Multicenter study of the validity and reliability of subjective global assessment in the hemodialysis popu-
lation. J Renal Nutr. 17(5): 336342.
U.S. Department of Agriculture (USDA). 2011. Online: www.choosemyplate.gov (accessed 2 June 2011).
108 Nutrition Therapy for Chronic Kidney Disease
Weekes, C., Elia, M., Emery, P. 2004. The development, validation, and reliability of a nutrition screening tool
based on the recommendations of the British Association for parenteral and enteral nutrition. Clin Nutr.
23:11041112.
Whitmire, S. 1998. Fluids and electrolytes. In Matarese, L., Gottschlich, M. Contemporary Nutrition Support
Practice. Philadelphia, PA: Saunders, 121144.
Williams, S. 2003. Nutrition assessment and medical nutrition therapy in patient care. In Williams, S.,
Schlenker, E., eds. Essentials of Nutrition and Diet Therapy, 8th edition. St Louis, MO: Mosby, 373390.
8 Nutrition for Chronic Kidney
Disease, Stages 13
Kim S. Stote
State University of New York
CONTENTS
8.1 General Principles: Chronic Kidney Disease, Stages 13..................................................... 109
8.2 Nutrition Care........................................................................................................................ 110
8.2.1 NKF-KDOQI Clinical Practice Guidelines for Nutrition..................................... 110
8.2.2 Medical Nutrition Therapy........................................................................................ 110
8.2.2.1 Medicare Reimbursement........................................................................... 110
8.3 Nutrition Intervention: Nutrition Prescription....................................................................... 111
8.3.1 Protein........................................................................................................................ 111
8.3.2 Energy........................................................................................................................ 113
8.3.3 Lipids......................................................................................................................... 113
8.3.4 Minerals..................................................................................................................... 114
8.3.4.1 Sodium........................................................................................................ 114
8.3.4.2 Potassium.................................................................................................... 115
8.3.4.3 Phosphorus.................................................................................................. 115
8.3.4.4 Calcium....................................................................................................... 116
8.3.4.5 Trace Elements............................................................................................ 116
8.3.5 Vitamins.................................................................................................................... 116
8.3.5.1 Fat-Soluble Vitamins.................................................................................. 116
8.3.5.2 Water-Soluble Vitamins.............................................................................. 117
8.3.6 Fluid........................................................................................................................... 119
8.3.7 Fiber........................................................................................................................... 119
8.4 Websites................................................................................................................................. 119
References....................................................................................................................................... 120
109
110 Nutrition Therapy for Chronic Kidney Disease
from Healthy People 2010. These new objectives recognize this by proposing a reduction in the
percentage of the U.S. population with CKD; reducing death rates among individuals with CKD;
and increasing the percentage of individuals with CKD who know they have impaired renal func-
tion (Healthy People, 2010). Moreover, the establishment of a World Kidney Day in 2006 by the
International Society of Nephrology and International Federation of Kidney Foundations was the
result of recognition that CKD is a threat to global public health (Collins et al., 2006).
disease associated with a reduction in function not severe enough to require dialysis or transplanta-
tion (glomerular filtration rate [GFR] 1350 mL/min/1.73 m2). Registered dietitians or nutrition
professionals are allowed to bill Medicare Part B for MNT services for CKD Stages 35, that is,
patients not receiving renal replacement therapy (Infante et al., 2002). MNT includes an initial
assessment of nutrition and lifestyle; nutrition counseling; information on managing lifestyle fac-
tors that affect diet; and follow-up visits to monitor patient progress in managing diet. Medicare
covers 3 h of one-on-one counseling services the first year and 2 h each year after that. More hours
of treatment with a physicians referral may be required if the individuals condition, treatment, or
diagnosis changes. A physician must prescribe these services and renew their referral yearly if the
need for continuing treatment extends into another calendar year. Private third-party insurance car-
riers may or may not follow similar diagnostic guidelines for coverage. Interestingly, reimbursement
through Medicare for CKD MNT may be underutilized. This may be due to underdiagnosed and
undertreated CKD (Aase, 2010; Infante and Michael, 2002).
diabetes therapy reduced the risk of microalbuminuria (defined as urinary albumin excretion, mea-
sured annually, = 40 mg per 24 h) and albuminuria (urinary albumin excretion = 300 mg per 24 h)
by 39% and 59%, respectively (DCCT, 1993). In addition, this trial showed that strict blood-glucose
control may be more significant than protein restriction in delaying the onset of renal failure in
individuals who have diabetes.
Consumption of high-protein diets in the short term leads to increased renal workload and an
increase in GFR (Brenner et al., 1982; Friedman, 2004). However, there is a paucity of research on
the long-term impact of protein intake on renal function in individuals with normal renal function or
mild renal insufficiency. Knight et al. examined the influence of protein intake on rate of renal func-
tion change in 1624 females, aged 4268 years, over an 11-year period in the Nurses Health Study.
Protein intake was assessed using food-frequency questionnaires. In women who began the study
with normal kidney function, the results showed no association between amounts of type of pro-
tein and decrease in kidney function over time. Even so, women who began with mildly decreased
kidney function showed a worsening in renal function with increasing amounts of nondairy animal
protein intake. Interestingly, vegetable and dairy proteins were not associated with a decrease in
kidney function (Knight et al., 2003). More research is required on the long-term impact of protein
intake in CKD Stages 13.
The NKF KDOQI Clinical Practice Guidelines for Nutrition in Chronic Renal Failure suggest
0.6 g of protein/kg/day when the GFR is <25 mL/min/1.73 m2, which corresponds approximately
to CKD Stages 45. However, dietary protein intake may be increased up to 0.75 g protein/kg/day
if dietary energy intake cannot be maintained (Kopple, 2001). Previous research found no favorable
effect from dietary protein intake more than the Dietary Reference Intakes (DRI; 0.8 g/kg/day);
therefore, it may be practical to recommend that dietary protein intake be increased to this level for
individuals in CKD Stages 13 with at least 50%60% of high-biologic-value protein to ensure an
adequate amount of essential amino acids. Protein consumption in Western diets shows that adults
typically consume 1.01.5 g of protein/kg/day (Fulgoni, 2008; Klahr et al., 1994; Mitch and Ikizler,
2010; Otten etal., 2006).
Current guidelines from The National Kidney Disease Education Program (NKDEP) recom-
mend limiting excessive dietary protein to 0.8 g protein/kg/day in persons without diabetes and to
0.81.0 g/kg/day of protein in persons with diabetes to slow progression of kidney disease (NKDEP,
2010). NKDEP is an initiative of the National Institutes of Health (NIH), United States, founded in
2001. Its mission is to reduce the morbidity and mortality caused by kidney damage and its compli-
cations. Recently, NKDEP, with the assistance of registered dietitians specializing in renal disease,
have developed strategies on how best to educate general practice dietitians, physicians, other health
professionals, and individuals with CKD. NKDEP has provided an overview guide for dietitians
for treating CKD patients who are not on dialysis. In addition, user-friendly education materials
for general practice dietitians have been developed. NKDEP (2010) has also supplied a wide array
of tools and resources for other health professionals, such as physicians, physician assistants, regis-
tered nurses, and laboratory professionals.
Updated standards of practice and standards of professional practice have been published for
general practice dietitians who see individuals with CKD (Brommage et al., 2009; Byham-Gray
et al., 2006). The American Dietetic Association also provides, through its Evidence Analysis
Library, current evidence-based renal guidelines for nutrition therapy (Blumberg-Kason et al.,
2006). In addition, practice recommendations for assisting patients with CKD have been published
for primary-care providers (Linden et al., 2010). These recommendations include a patient referral
to a dietitian for guidance on nutrition therapy for CKD.
One of the primary goals of nutrition therapy is to maintain the individuals nutritional status. It
is essential to maintain body protein stores to prevent protein-energy malnutrition. Decline of nutri-
tional status is present when GFR falls below 60 mL/min, which begins at CKD Stage 2. Protein-
energy malnutrition is a risk factor for morbidity and mortality in individuals with CKD (American
Dietetic Association, 2010; Byham-Gray et al., 2008; Mitch et al., 2010).
Nutrition for Chronic Kidney Disease, Stages 13 113
8.3.2 Energy
Total energy expenditure (TEE) includes resting energy expenditure (REE), physical activity, and ther-
mogenesis (the thermic effect of food). Resting expenditure accounts for 60%75%; physical activity
accounts for 15%30%; and thermogenesis accounts for 10% of TEE (Cuppari and Avesani, 2004).
Previous research with individuals with CKD not receiving renal replacement therapy shows
that the energy requirements are comparable to the general population. Research indicates that a
diet providing approximately 35 kcal/kg/day is needed to maintain a neutral nitrogen balance, to
maintain a higher serum albumin concentration, to support a more normal body composition, and
to improve protein utilization. In CKD individuals 60 years of age who are less physically active,
an energy intake of 3035 kcal/kg/day may be appropriate (Kopple, 2001; KDOQI, 2000).
The use of REE prediction equations such as the Harris and Benedict and the Schofield equations
has been shown to overestimate REE in individuals with CKD. More research is required to develop
population-specific equations that can adequately estimate the energy requirements of individuals
with CKD, though the prediction equations may be useful as an initial guide for dietary planning
(Kamimura et al., 2011). Ultimately, the energy requirements for CKD Stages 13 should be deter-
mined by age, gender, physical activity, nutritional status, and other comorbidities. It is also recom-
mended that the individuals nutritional status be monitored on a regular basis and adjustments for
energy requirements be made as needed.
Obesity is an escalating major health problem in the world. It contributes to increased hypertension
and type 2 diabetes, which are the major causes of end-stage renal disease. The energy requirements
of obese (body mass index 30 kg/m2) or overweight (body mass index 25.029.9 kg/m2) individ-
uals should be decreased. Structured programs emphasizing lifestyle changes including moder-
ate weight loss (7% of body weight) and regular physical activity should be encouraged (Kopple,
2010). In addition, dietary strategies, including decreasing calories and fat, may reduce the risk for
developing diabetes (American Diabetes Association, 2011).
8.3.3 Lipids
During CKD Stages 13, there is a high prevalence of dyslipidemias and CVD. Controlling dys-
lipidemia may reduce the rate of decline in the GFR (Beto, 2004b; Fried et al., 2001; K/DOQI,
2002). While few studies have examined the effects of fat modification on CKD progression among
individuals with CKD, it is practical to recommend the National Cholesterol Education Program
(NCEP) Adult Treatment Panel (ATP III) to individuals with CKD Stages 13. The NKF KDOQI
recommended that NCEP ATP III guidelines are generally applicable to CKD Stages 13 (KDOQI,
2000). The National Heart, Lung, and Blood Institute of the NIH began the NCEP in November
1985. The goal of NCEP was to decrease illness and death from CVD in the United States by ulti-
mately decreasing the percentage of Americans who have elevated cholesterol levels. The NCEP
strived to raise awareness about high blood cholesterol through education aimed at the American
public and health professionals (NCEP, 2001).
In 1988, the ATP of the NCEP released clinical guidelines for the dietary and drug management
of hypercholesterolemia. These guidelines were revised in 1993 and in 2000. The Third Report
of the Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults
(ATP III) presents the most recent updated clinical guidelines. The NCEP periodically produces
ATP clinical updates as determined by advances in the science of cholesterol management. Each
of the ATP reports, ATP I, ATP II, and now ATP III, have had a major theme. ATP I outlined a
strategy for primary prevention of CVD in individuals with elevated levels of low-density lipopro-
tein (LDL) cholesterol (160 mg/dL) or those with borderline high LDL cholesterol (130159 mg/
dL) with more than two risk factors. ATP II acknowledged the importance of this approach and
added a new feature, which was the intensive management of LDL cholesterol in individuals with
established CVD. For individuals with CVD, ATP II set forth a new lower LDL cholesterol goal of
114 Nutrition Therapy for Chronic Kidney Disease
100 mg/dL. While the core recommendations in ATP III remain as previously defined, the main
features are a greater focus on primary prevention in individuals with multiple risk factors, which
calls for more-intensive LDL cholesterollowering therapy and identification of LDL cholesterol <
100 mg/dL as optimal. According to ATP III, candidates for cholesterol diet therapy are those with:
1. LDL cholesterol > 160 mg/dL with zero to one heart-disease risk factors and a 10-year risk
for CVD of <10%;
2. LDL cholesterol > 130 mg/dL with two or more heart-disease risk factors and a 10-year
risk of CVD of 20%;
3. LDL cholesterol level > 100 mg/dL and established CVD.
The 10-year risk is estimated from the Framingham risk scores. The risk factors included in the
calculation are age, total cholesterol, high-density lipoprotein cholesterol, systolic blood pressure,
treatment for hypertension, and smoking (NCEP, 2001).
As in the previous NCEP guidelines, lowering LDL cholesterol is the goal of dietary manage-
ment, and the aim is to achieve an LDL cholesterol level that is 30 mg/dL below the initial value.
ATP III recommends the lifestyle approach, termed Therapeutic Lifestyles Changes (TLC), which
includes reducing the intake of saturated fatty acids to <7% of energy and reducing the intake of
dietary cholesterol to <200 mg/day, for those individuals with elevated LDL cholesterol prior to
the initiation of drug therapy. These dietary guidelines are generally consistent with other dietary
recommendations in the United States. The TLC diet recommends total fat intake may range from
25% to 35% of energy with polyunsaturated fatty acids providing up to 10% of energy and mono-
unsaturated fatty acids providing up to 20% of energy. Trans fatty acids should also be limited.
Carbohydrate intake should be 50%60% of total energy and derived mostly from foods high in
complex carbohydrates. Fiber intake should be 2030 g/day (NCEP, 2001).
Omega-3 fatty acids have been shown in epidemiological and clinical trials to reduce the inci-
dence of CVD. Epidemiological studies suggest that individuals at risk for CVD benefit from the
consumption of plant- and marine-derived omega-3 fatty acids. However, the recommended intake
remains uncertain. The American Heart Association Dietary Guidelines recommends the general
population to include at least two servings of fish per week (particularly fatty fish) along with veg-
etable oils (soybean, canola, walnut, flaxseed) and food sources (walnuts, flaxseeds) that are high in
-linolenic acid (Kris-Etherton et al., 2003). It may be practical to recommend these guidelines as
there is limited research on the effects of consuming foods high in omega-3 fatty acids in individu-
als with CKD Stages 13. Long-term omega-3 fatty acid supplement use has not been rigorously
studied in individuals with CKD Stages 13 (Friedman, 2010).
8.3.4 Minerals
8.3.4.1 Sodium
Sodium is freely filtered by the glomerulus. In healthy individuals, 99.5% of sodium is reabsorbed.
The GFR and fractional tubular reabsorption decrease gradually as CKD progresses. Many individ-
uals with CKD, therefore, are able to maintain sodium balance with normal sodium intake (Mitch
et al., 2010). The INTERSALT Study was an international epidemiological study that included
10,079 men and women, aged 2059 years, from 52 places around the world. Results showed a posi-
tive correlation between sodium excretion and both systolic and diastolic blood pressure; the aver-
age level of blood pressure of individuals in a country increases with salt intake (Stamler, 1997). For
individuals with hypertension, reduction of dietary sodium has also been associated with improved
blood pressure control (Appel et al., 2010).
The major source of sodium in the diet is added salt in the form of sodium chloride. Sodium com-
prises 40% by weight of sodium chloride. One teaspoon of salt has 2300 mg of sodium. Processed
foods account for approximately 77% of total sodium consumed as salt is used extensively in food
Nutrition for Chronic Kidney Disease, Stages 13 115
processing and manufacturing; 10% comes from table salt and cooking. Sodium intake varies
throughout Western countries from 1500 mg/day to more than 5000 mg/day. The estimated amount
of sodium consumed by adults in the United States ranges from 3000 to 5000 mg/day (Mitch et al.,
2010; Shils et al., 2006). The Dietary Guidelines for Americans recommend a daily sodium intake
of less than 2300 mg for the general adult population. Moreover, hypertensive individuals, blacks,
and middle-aged and older adults would benefit from reducing their sodium intake even further.
Because these groups collectively make up approximately 70% of adults in the United States, the
recommended sodium intake for the general population is 1500 mg/day. (Dietary Guidelines, 2010;
Savica et al., 2010). This recommendation is particularly challenging given food processing meth-
ods and patterns of sodium consumption. Strategies for reducing sodium intake should provide for
a gradual reduction to allow taste perception to adjust.
Guidelines from NKDEP recommend limiting dietary sodium to 2300 mg/day or less to slow
progression of kidney disease. It should be noted, however, that reduced sodium intake has been
associated with further renal impairment in some renal diseases; thus, each individual with CKD
Stages 13 will need to be managed individually. The NKDEP website provides user-friendly edu-
cation materials for lowering dietary sodium (NKDEP, 2010).
The importance of dietary modification in the prevention and treatment of hypertension is well
recognized. The Dietary Approaches to Stop Hypertension (DASH) eating plan incorporates reduc-
tion in sodium; inclusion of fruits, vegetables, and whole grains; and limitation of fats consistent with
the TLC diet to lower blood cholesterol. The DASH diet provides an eating pattern that limits sodium
levels between 1500 and 2400 mg/day. In addition, it is high in potassium, calcium, magnesium, and
fiber (Appel et al., 2010). While the DASH diet is beneficial in lowering blood pressure, the increased
potassium and phosphorus intakes that may result may lead to hyperkalemia and hyperphosphatemia
in individuals with GFR < 60 mL/min/1.73 m2, corresponding to the beginning of CKD Stage 2.
Persons with CKD will require individualized nutrition therapy (Byham-Gray et al., 2008).
The 7th Report of the Joint National Treatment of High Blood Pressure also provides lifestyle
modification guidelines to manage hypertension. These include weight loss, reducing sodium intake
to 2400 mg/day, limiting alcohol consumption to no more than two drinks per day, and increasing
physical activity (Chobanian et al., 2003; Cushman, 2007).
8.3.4.2 Potassium
Dietary potassium is typically not restricted in CKD Stages 13. The prevalence of hypertension
and hyperlipidemia with risk for CVD, coronary artery disease (CAD), and left ventricular hyper-
trophy is higher in individuals with CKD compared to the general population; therefore, serum
potassium should be monitored because of the effect of some antihypertensive agents, such as
renin-angiotensin system antagonists, on potassium excretion. Serum potassium concentrations
should be maintained between 3.5 and 5.0 mEq/L. Dietary potassium should be limited when
serum potassium > 5.0 mEq/L (Beto et al., 2004a; Kent, 2005; NKDEP, 2010).
8.3.4.3 Phosphorus
The optimal intake of dietary phosphorus for individuals with CKD Stages 13 has not been well
established. Hyperphosphatemia, elevated parathyroid hormone (PTH), secondary parathyroidism
with depressed serum calcium and vitamin D deficiency are metabolic disturbances that require
early detection and treatment to prevent CKD mineral and bone disorder (CKD-MBD). CKD-MBD
is a systematic disorder of mineral and bone metabolism due to CKD manifested by either one or a
combination of abnormalities of calcium, phosphorus, PTH, or vitamin D metabolism; abnormali-
ties in bone turnover, mineralization, volume, linear growth, or strength; and vascular or other soft-
tissue calcification. Current guidelines on management of CKD-MBD reflect consensus rather than
high-grade evidence. According to NKF KDOQI U.S. Commentary on the 2009 KDIGO Clinical
Practice Guideline for the Diagnosis, Evaluation, and Treatment of CKD-MBD, changes in levels
of the biomarkers of CKD-MBD (phosphorus, calcium, PTH, and alkaline phosphatase) may begin
116 Nutrition Therapy for Chronic Kidney Disease
in CKD Stage 3. Treatment of CKD-MBD needs to be individualized and may include nutrition
counseling and education on dietary phosphate restriction, use of phosphate binders, and calcium
and vitamin D supplementation. Serum phosphorus concentrations should be maintained between
2.7 and 4.6 mg/dL. If serum phosphorus is elevated, dietary phosphorus restriction may be indicated
(Uhlig et al., 2010). Assessing dietary intake, especially protein intake, is recommended. Phosphorus
is present in a several foods, mainly protein sources. Dietary protein restriction decreases phospho-
rus intake. If further restriction of dietary phosphorus is required, nutrition counseling and educa-
tion may be provided to teach the individual to reduce consumption of foods with added phosphorus
such as fast foods, convenience foods, and processed foods. Individuals with elevated phosphorus
should be educated to read ingredient lists for phos to identify foods with phosphate additives, as
these additives may be more readily absorbed versus food sources. Phosphorus additives are used by
food manufacturers to enhance flavor and stability (NKDEP, 2010). Average phosphorus consump-
tion of the general population in the United States ranges from approximately 1550 and 1100 mg,
in men and women aged 20 years and older, respectively (USDA, 2010). NKDEP (2010) provides
user-friendly education materials for lowering dietary phosphorus on its website.
8.3.4.4 Calcium
Dietary calcium recommendations for CKD Stages 13 have yet to be established (NKDEP, 2010).
Serum calcium concentrations should be maintained within 8.510.2 mg/dL or reference range.
NKF KDOQI U.S. Commentary on the 2009 KDIGO Clinical Practice Guideline for the Diagnosis,
Evaluation, and Treatment of CKD-MBD suggests monitoring serum calcium concentrations in
individuals with CKD Stage 3 every 612 months. In addition, the committee did not recommend
discarding the corrected calcium measurement, although data have suggested that this measurement
is not more accurate than total calcium alone. Ionized calcium is considered a more accurate mea-
sure, but it is currently not practical or cost-efficient. Hypoalbuminemia may contribute to falsely
low calcium concentration because the calcium is bound to protein (Uhlig et al., 2010). A common
formula to determine corrected calcium as is (Kent, 2005):
The DRI (the standards in use for the United States and Canada as determined by the committee
of the Food and Nutrition Board of the National Academy of Sciences Institute of Medicine work-
ing in association with Health Canada) for calcium indicate for the general population, women aged
1950 years and men up to 71 years require on average 800 mg of calcium per day. Women over
50 and both men and women 71 years and older should take 1000mg/day on average (IOM, 2010).
8.3.5 Vitamins
8.3.5.1 Fat-Soluble Vitamins
Vitamin D supplementation should be individualized in CKD Stages 13. Vitamin D metabo-
lism is disordered in CKD. Abnormalities may begin in CKD Stage 3. The renal tubular cell
primarily activates 25-hydroxyvitamin D (calcidiol) to 1,25-dihydroxyvitamin D (calcitriol or
Nutrition for Chronic Kidney Disease, Stages 13 117
active vitaminD). Reduction of kidney function results in decreased production and conversion
of calcidiol to calcitriol. Furthermore, there may be related imbalances of calcium, phosphorus,
and PTH. Adequacy of vitamin D is typically measured by the circulating concentrations of
25-hydroxyvitamin D, which is the combined product of synthesis from sun exposure and dietary
sources. In adults, the majority of circulating 25-hydroxyvitamin D originates from ultraviolet B
ray exposure. If the serum level of 25-hydroxyvitamin D is less than 30 ng/mL supplementation
may be indicated (Mitch, 2010; NKDEP, 2010; Uhlig, 2010). The dietary supplement cholecalcif-
erol (vitamin D3) may be used in early stages of CKD to increase vitamin D concentrations. NKF
KDOQI U.S. Commentary on the 2009 KDIGO Clinical Practice Guideline for the Diagnosis,
Evaluation, and Treatment of CKD-MBD suggest that individuals with CKD vitamin D defi-
ciency and insufficiency should use treatment strategies recommended for the general population.
In addition, 25-hydroxyvitamin D (calcidiol) may be measured with repeated testing determined
by baseline values and therapeutic interventions. There are limited data about whether vitamin
D concentrations should differ between the general population and those with CKD. Vitamin D
deficiency or insufficiency may cause individuals with CKD to have increased PTH concentra-
tions (Uhlig et al., 2010). Epidemiological studies show an association between low vitamin D
concentrations and adverse clinical outcomes such as cancer and increased mortality (Holick,
2007). There is, however, a lack of data from clinical trials with vitamin D to confirm these clini-
cal outcomes. It is recommended that clinicians individualize the decision to measure vitamin D.
A practical approach would be to occasionally measure 25-hydroxyvitamin D in individuals with
CKD and start treatment if the concentration is low. Recommendations for the general population
for vitamin D repletion specify cholecalciferol dose of 10002000 IU/day. Serum concentrations
of calcium, phosphorus, and PTH concentrations should be monitored when vitamin D dietary
supplements are utilized (Uhlig et al., 2010).
In 2010, the DRI for vitamin D for the general population in the United States and Canada
were updated by an appointed committee from the Institute of Medicine, utilizing current research
on clinical outcomes associated with vitamin D. Previous recommendations for the vitamin sug-
gested an adequate intake for vitamin D of 200 IU for men and women aged 1950 years. The
2010 recommendation for vitamin D has increased to 400 IU/day. Individuals aged 71 years and
older may require as much as 800 IU/day. The committee reported that there is not yet sufficient
research about the health benefits of vitamin D beyond bone health. They also reported that the
measurements, or cut-points, of sufficiency and deficiency used by laboratories to report vitamin D
concentrations have not been set based upon rigorous scientific research. No central authority has
determined which cut-points to use. An individual may be determined to be vitamin D sufficient
or deficient, depending upon the laboratory where the serum was tested. The committee concluded
that the number of individuals with vitamin D deficiency in North America may be overestimated as
a result of laboratories using cut-points that may be higher than recommended. Laboratories should
assist clinicians in interpretation of vitamin D concentrations by reporting assay characteristics and
methodology utilized (IOM, 2010).
Supplementation of other fat-soluble vitamins such as vitamins A, E, and K has not been well
established in CKD Stages 13. Current recommendations suggest that supplementation of vitamins
A, E, and K should be avoided, as these may accumulate more rapidly in CKD (Mitch et al., 2010;
Shils et al., 2006).
Phosphorus Calcium
Stage Protein (g/kg/day) Energy Sodium (g/day) Potassium (g/day) (g/day) (mg/day) Vitamins
1. GFR 90130 mL/min Nondiabetic: 0.8 g/kg/day, Determined by 2300 mg or less Typically no restriction, Monitor and DRI, individualize, DRI, individualize
Diabetic: 0.81.0 g/kg/day, energy restrict if serum level is restrict if serum maintain serum for vitamin D
50% high biologic value expenditure 5.0 mEq/L level >4.6 mg/dL calcium within
reference range
2. GFR 6089 mL/min Same as Stage 1 Same as Stage 1 Same as Stage 1 Same as Stage 1 Same as Stage 1 Same as Stage 1 DRI, individualize
for vitamin D
3. GFR 3059 mL/min Same as Stage 1 Same as Stage 1 Same as Stage 1 Same as Stage 1 Same as Stage 1 Same as Stage 1 DRI, B-complex
increase urinary nutrient loss, and alter normal pathways of nutrient metabolism (Mitch et al., 2010;
Shils et al., 2006).
The use of nutrient and dietary supplements is prevalent and increasing. Clinicians should regu-
larly assess the individuals intake of vitamin supplements, other dietary supplements, and fortified
foods that may be a part of dietary intake (Marra and Boyar, 2009; Skeie et al., 2009).
8.3.6 Fluid
Fluid requirements in CKD Stages 13 are typically unrestricted with normal urine output (Byham-
Gray and Wiesen, 2004; Byham-Gray et al., 2008).
8.3.7 Fiber
Fiber recommendations for the general population are that individuals should consume adequate
amounts of dietary fiber from a variety of plant foods. Research in the general population suggests
that a high dietary fiber intake may reduce the incidence of constipation, irritable bowel syndrome,
diverticulitis, and colon cancer. In addition, fiber may improve glucose tolerance in those with dia-
betes. Fiber consumption in the United States is approximately 15 g/day. The recommended DRIs
call for consumption of 14 g of dietary fiber per 1000 calories, or 25 g of fiber per day for women
and 38 g of fiber per day for men (Slavin, 2008). The appropriate amount and kinds of fiber have not
been clearly established in CKD Stages 13. Fiber intake should be individualized for those with
CKD Stages 13 based upon assessment of current dietary intake, gender, age, nutritional status,
and other comorbidities.
8.4 WEBSITES
American Dietetic Association
http://www.eatright.org/
American Dietetic AssociationNutrition Care Manual
http://nutritioncaremanual.org/
American Dietetic AssociationEvidence Analysis Library
http://www.adaevidencelibrary.com/
American Dietetic AssociationRenal Dietitians Practice Group
http://www.renalnutrition.org/
National Kidney Disease Education Program
http://nkdep.nih.gov/
National Kidney Disease Education ProgramEducation materials and resources for health
professionals
http://nkdep.nih.gov/professionals/index.htm
National Kidney Foundation
http://www.kidney.org/
National Kidney Foundation KidneyKidney Disease Outcomes Quality Initiative (NKF-KDOQI)
http://www.kidney.org/Professionals/kdoqi/
National Kidney FoundationCouncil on Renal Nutrition
http://www.kidney.org/professionals/CRN/
International Society of Renal Nutrition and Metabolism
http://www.kidney.org/ISRNM/
Canadian Association of Nephrology Dietitians
http://www.renalrd.ca/
Kidney Disease Improving Global Outcomes
http://www.kdigo.org/
120 Nutrition Therapy for Chronic Kidney Disease
REFERENCES
Aase, S. 2010. Kidney friendly: What the National Kidney Disease Education Program strategic plan means for
dietetic practice. J Am Diet Assoc. 110: 346351.
American Diabetes Association. 2011. Executive summary: Standards of medical care in diabetes2011.
Diabetes Care. 34(Suppl 1): S4S17.
American Dietetic Association. 2010. Nutrition Care Manual, Chronic Kidney Disease. Chicago, IL: American
Dietetic Association.
Aparicio, M. 2009. Protein intake and chronic kidney disease: Literature review, 2003 to 2008. J Renal Nutr.
19: S5S8.
Appel, L., Wright, J., Jr., Greene, T., et al. 2010. Intensive blood-pressure control in hypertensive chronic kid-
ney disease. N Engl J Med. 363: 918929.
Brenner, B., Meyer, T., Hostetter, T. 1982. Dietary protein intake and the progressive nature of kidney disease:
The role of hemodynamically mediated glomerular injury in the pathogenesis of progressive glomerular
sclerosis in aging, renal ablation, and intrinsic renal disease. N Engl J Med. 307: 652659.
Brommage, D., Karalis, M., Martin, C., et al. 2009. American Dietetic Association and the National Kidney
Foundation Standards of Practice and Standards of Professional Performance for registered dietitians
(generalist, specialty, and advanced) in nephrology care. J Renal Nutr. 19: 345356.
Beto, J., Bansal, V. 2004a. Medical nutrition therapy in chronic kidney failure: Integrating clinical practice
guidelines. J Am Diet Assoc. 104: 404409.
Beto, J., Bansal, V. 2004b. Nutrition interventions to address cardiovascular outcomes in chronic kidney dis-
ease. Adv Chronic Kidney Dis. 11: 391397.
Blumberg-Kason, S., Lipscomb, R. 2006. Evidence-based nutrition practice guidelines: A valuable resource in
the evidence analysis library. J Am Diet Assoc. 106: 19351936.
Byham-Gray, L., Wiesen, K., eds. 2004.A Clinical Guide to Nutrition Care in Kidney Disease. Chicago, IL:
American Dietetic Association.
Byham-Gray, L., Burrowes, J., Chertow, G., eds. 2008. Nutrition in Kidney Disease. Totowa, NJ: Humana
Press.
Byham-Gray, L., Wiesen, K., Goode, J. 2006. Scope of practice in renal nutrition. J Renal Nutr. 16: 160167.
Chobanian, A., Bakris, G., Black, H., et al. 2003. The Seventh Report of the Joint National Committee on
Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: The JNC 7 report. JAMA.
289: 25602572.
Collins, A., Couser, W., Dirks, J., et al. 2006. World Kidney Day: An idea whose time has come. Kidney Int.
69: 781782.
Cuppari, L., Avesani, C. 2004. Energy requirements in patients with chronic kidney disease. J Renal Nutr.14:
121126.
Cushman, W. 2007. JNC-7 guidelines: Are they still relevant? Curr Hypertens Rep. 9: 380386.
Diabetes Control and Complications Trial Research Group. 1993. The effect of intensive treatment of diabetes
on the development and progression of long-term complications in insulin-dependent diabetes mellitus.
N Engl J Med. 329: 977986.
Dietary Guidelines for Americans. 2010. http://www.cnpp.usda.gov/Publications/DietaryGuidelines/2010/
PolicyDoc/Chapter3.pdf (accessed June 8, 2011).
Eckardt, K., Berns, J., Rocco, M., et al. 2009. Definition and classification of CKD: The debate should be about
patient prognosisa position statement from KDOQI and KDIGO. Am J Kidney Dis. 53: 915920.
Escott-Stump, S. 2008. Nutrition and Diagnosis-Related Care, 6th edn. Philadelphia, PA: Lippincott, Williams
& Wilkins.
Fox, T. 2000. Institute of Medicine urges Medicare coverage of medical nutrition therapy. J Am Diet Assoc.
100: 166.
Fried, L., Orchard, T., Kasiske, B. 2001. Effect of lipid reduction on the progression of renal disease: A meta-
analysis. Kidney Int. 59: 260269.
Nutrition for Chronic Kidney Disease, Stages 13 121
Friedman, A. 2004. High-protein diets: Potential effects on the kidney in renal health and disease. Am J Kidney
Dis. 44: 950962.
Friedman, A. 2010. Omega-3 fatty acid supplementation in advanced kidney disease. Semin Dial. 23: 396400.
Fulgoni, V. 2008. 3rd. Current protein intake in America: Analysis of the National Health and Nutrition
Examination Survey, 20032004. Am J Clin Nutr. 87: 1554S1557S.
Healthy People. 2010. http://www.healthypeople.gov/hp2020/ (accessed December 1, 2010).
Hemmelgarn, B., Manns, B., Lloyd, A., et al. 2010. Relation between kidney function, proteinuria, and adverse
outcomes. JAMA. 303: 423429.
Holick, M. 2007. Vitamin D deficiency. N Engl J Med. 357: 266281.
Infante, M., Michael, P. 2002. Medicare Part B coverage and billing for medical nutrition therapy. J Am Diet
Assoc. 102: 32.
Institute of Medicine (IOM). 2010. Dietary reference intakes for calcium and vitamin D. http://www.iom.
edu/Reports/2010/Dietary-Reference-Intakes-for-Calcium-and-Vitamin-D.aspx (accessed December 1,
2010).
Kamimura, M., Avesani, C., Bazanelli, A., et al. 2011. Are prediction equations reliable for estimating resting
energy expenditure in chronic kidney disease patients? Nephrol Dial Transplant. 26: 544550.
Kasiske, B., Lakatua, J., Ma, J., et al. 1998. A meta-analysis of the effects of dietary protein restriction on the
rate of decline in renal function. Am J Kidney Dis. 31: 954961.
K/DOQI. 2000. Clinical practice guidelines for nutrition in chronic renal failure. National Kidney Foundation.
Am J Kidney Dis. 35: S1S140.
K/DOQI. 2002. Clinical practice guidelines for chronic kidney disease: Evaluation, classification, and stratifi-
cation. National Kidney Foundation. Am J Kidney Dis. 39: S1S266.
Kent, P. 2005. Integrating clinical nutrition practice guidelines in chronic kidney disease. Nutr Clin Pract. 20:
213217.
Klahr, S., Levey, A., Beck, G., et al. 1994. The effects of dietary protein restriction and blood-pressure control
on the progression of chronic renal disease. Modification of Diet in Renal Disease Study Group. N Engl
J Med. 330: 877884.
Knight, E., Stampfer, M., Hankinson, S., et al. 2003. The impact of protein intake on renal function decline in
women with normal renal function or mild renal insufficiency. Ann Intern Med. 138: 460467.
Kopple, J. 2001. National kidney foundation K/DOQI clinical practice guidelines for nutrition in chronic renal
failure. Am J Kidney Dis. 37: S66S70.
Kopple, J. 2010. Obesity and chronic kidney disease. J Renal Nutr. 20: S29S30.
Kris-Etherton, P., Harris, W., Appel, L. 2003. Omega-3 fatty acids and cardiovascular disease: New recommen-
dations from the American Heart Association. Arterioscler Thromb Vasc Biol. 23: 151152.
Levey, A., Eckardt, K., Tsukamoto, Y., et al. 2005. Definition and classification of chronic kidney disease:
A position statement from Kidney Disease: Improving Global Outcomes (KDIGO). Kidney Int. 67:
20892100.
Levey, A., Greene, T., Sarnak, M., et al. 2006. Effect of dietary protein restriction on the progression of kidney
disease: Long-term follow-up of the Modification of Diet in Renal Disease (MDRD) Study. Am J Kidney
Dis. 48: 879888.
Linden, A., Biuso, T., Butterworth, S.W. 2010. Help patients with chronic kidney disease stave off dialysis.
JFam Pract. 59: 212219.
Mafra, D., Cuppari, L., Favaro, D., et al. 2004. Zinc levels after iron supplementation in patients with chronic
kidney disease. J Ren Nutr. 14: 164169.
Marra, M., Boyar, A. 2009. Position of the American Dietetic Association: Nutrient supplementation. J Am Diet
Assoc. 109: 20732085.
Mitch, W., Ikizler, T., eds. 2010. Handbook of Nutrition and the Kidney, 6th edn. Philadelphia, PA: Lippincott,
Williams & Wilkins.
National Cholesterol Education Program Expert Panel. 2001. Executive summary on detection, evaluation,
and treatment of high blood cholesterol in adults (Adult Treatment Panel III). JAMA. 285: 24862497.
National Kidney Disease Education Program. 2010. http://nkdep.nih.gov/professionals/index.htm (accessed
December 1, 2010).
Otten, J., Hellwig, J., Meyers, L., eds. 2006. Dietary Reference Intakes, 6th edn. Washington, DC: National
Academy of Sciences.
Saran, R., Shahinian, V. 2010. CKD: A pandemic calling for concerted public health action. Adv Chronic
Kidney Dis. 17: 213214.
Saran, R., Hedgeman, E., Huseini, M., et al. 2010. Surveillance of chronic kidney disease around the world:
Tracking and reining in a global problem. Adv Chronic Kidney Dis. 17: 271281.
122 Nutrition Therapy for Chronic Kidney Disease
Savica, V., Bellinghieri, G., Kopple, J.D. 2010. The effect of nutrition on blood pressure. Annu Rev Nutr. 30:
365401.
Shils, M., Shike, M., Ross, A., et al., ed. 2006. Modern Nutrition in Health and Disease, 10th edn. Philadelphia,
PA: Lippincott, Williams & Wilkins.
Skeie, G., Braaten, T., Hjartaker, A., et al. 2009. Use of dietary supplements in the European Prospective
Investigation into Cancer and Nutrition calibration study. Eur J Clin Nutr. 63(Suppl 4): S226S238.
Slavin, J. 2008. Position of the American Dietetic Association: Health implications of dietary fiber. J Am Diet
Assoc. 108: 17161731.
Stamler, J. 1997. The INTERSALT Study: Background, methods, findings, and implications. Am J Clin Nutr.
65: 626S642S.
Uhlig, K., Berns, J., Kestenbaum, B., et al. 2010. KDOQI US commentary on the 2009 KDIGO Clinical
Practice Guideline for the Diagnosis, Evaluation, and Treatment of CKD-Mineral and Bone Disorder
(CKD-MBD). Am J Kidney Dis. 55: 773799.
U.S. Department of Agriculture. 2010. Nutrient intakes from food: Mean amounts consumed per individual, by
gender and age. What We Eat in America, NHANES 20072008. Agricultural Research Service.
Whaley-Connell, A., Sowers, J., Stevens, L., et al. 2008. CKD in the United States: Kidney Early Evaluation
Program (KEEP) and National Health and Nutrition Examination Survey (NHANES) 19992004. Am
JKidney Dis. 51: S13S20.
Zhang, Q., Rothenbacher, D. 2008. Prevalence of chronic kidney disease in population-based studies:
Systematic review. BMC Public Health. 8: 117.
9 Nutrition for Chronic
Kidney Disease, Stage 4
Ann Grothe
DaVita Peninsula Dialysis
CONTENTS
9.1 Introduction........................................................................................................................... 123
9.2 Background............................................................................................................................ 124
9.3 Assessment............................................................................................................................ 124
9.4 Nutritional Recommendations for Patients with CKD 4Macronutrients.......................... 125
9.4.1 Protein........................................................................................................................ 125
9.4.2 Energy........................................................................................................................ 126
9.5 Nutritional Recommendations for Patients with CKD 4Micronutrients........................... 127
9.5.1 Bone Metabolism and Phosphorus............................................................................ 127
9.5.2 Bone Metabolism and Calcium................................................................................. 128
9.5.3 Bone Metabolism and PTH....................................................................................... 128
9.6 Key Electrolytes in CKD 4.................................................................................................... 128
9.7 Vitamins and Minerals.......................................................................................................... 129
9.7.1 Vitamin D.................................................................................................................. 129
9.7.2 Anemia...................................................................................................................... 129
9.8 Comorbities and CKD 4........................................................................................................ 129
9.8.1 Diabetes..................................................................................................................... 130
9.8.2 Cardiovascular Disease............................................................................................. 130
9.8.3 Obesity....................................................................................................................... 130
9.9 Medical Nutrition Therapy.................................................................................................... 131
9.10 Education............................................................................................................................... 131
9.11 Summary............................................................................................................................... 132
References....................................................................................................................................... 133
9.1 INTRODUCTION
Chronic kidney disease Stage 4 (CKD 4) is a transitional stage with significant management chal-
lenges due to the wide variation in symptoms, lab values, and overall patient presentation. Nutrition
plays a key role not only in the management of progression of the disease but also in minimizing
the impact of the comorbidities seen in patients. Nutrition also affects the presentation of symp-
toms and long-term outcome of treatment of these patients when they undergo renal replacement
therapy (RRT). Nutrition management during this critical predialysis stage must be individualized
and closely monitored to maximize efficacy and avoid overrestriction of dietary intake.
Standards of care, specifically, with regard to the use of protein restriction remain controversial,
requiring the practitioner to balance the competing needs of decreasing the toxin load on the kid-
neys while limiting protein malnutrition. Goals of nutritional therapy include decreasing uremic
toxins, promoting adequate nutritional status, and utilizing dietary strategies to support manage-
ment of comorbidities. Establishing good self-management skills is vital for the patient to achieve
123
124 Nutrition Therapy for Chronic Kidney Disease
and maintain the necessary behavior and lifestyle changes needed to reach these goals and to ulti-
mately delay the progression to end-stage renal disease (ESRD; Beto and Bansal, 2004).
9.2 BACKGROUND
CKD 4 is historically defined based on an estimated glomerular filtration rate (eGFR) of 1529
mL/min. However, critics accuse the use of creatinine-based calculation for underestimating the
actual function of the kidneys and propose the use of more sensitive equations. The U.S. Renal Data
System estimates that about 14.2%15.2% (depending on which equation is used) of the popula-
tion is with CKD (U.S. Renal Data System, 2010). In addition, it reports an increasing incidence of
diabetes, hyptertension, and cardiovascular disease (CVD) as eGFR decreases. This is significant
given that the risk factors for CKD include diabetes, hypertension, obesity, family history, age,
and race (U.S. Renal Data System, 2010). Information on stage-specific incidence of CKD has
improved since Medicare started using stage-specific ICD-9 codes for tracking and identification
of CKD. Based on 2008 Medicare data, 400,000 people were diagnosed with CKD 4 (U.S. Renal
Data System, 2010).
Nutrition management for the patients with CKD 4 is highly individual and complex. The goals
of nutrition management comprise managing symptoms and comorbidities, delaying progression
of the disease, and optimizing nutritional status. CKD 4 is characterized by changes in the lab val-
ues and the associated symptoms as the body becomes less able to cope with the failing kidneys.
Fluid and electrolyte imbalances become more pronounced, affecting acidbase balance and regu-
lation of sodium and potassium. Patients often present with symptoms such as metabolic acidosis,
hyperkalemia, and increased edema. Mineral metabolism with respect to calcium and phosphorus
regulation as well as probable deficiency of 25-hydroxy vitamin D should be addressed. Hormonal
abnormalities and/or deficiencies in erythropoietin (EPO) and increase in parathyroid hormone
(PTH) increase the risk of anemia and secondary hyperparathyroidism in patients. Except for
anemia and edema, there are often few symptoms reported with the aforementioned changes in
physiology. However, alterations in gastrointestinal (GI) functions, such as anorexia, nausea and
vomiting, and altered taste are frequently reported. These symptoms are related to the increase in
uremic toxins. Weight changes related to fluid balance as well as decrease in dietary intake may
also be seen.
9.3 ASSESSMENT
Nutritional assessment of patients with stage 4 CKD must be comprehensive and include medical
and health history, food/nutrition-related history, anthropometrics, and biochemical parameters
(ADA, 2010). A thorough review is also important to identify medications such as blood pres-
sure medications, diuretics, or blood thinners, which may affect key lab values in patients with
CKD 4. Anthropometrics should include height, weight (edema-free), body mass index (BMI),
and recent blood pressure. It is important to note changes in weight that are not related to fluid
status and that are related to changes in medications. The National Kidney Foundation Kidney
Dialysis Outcome Quality Initiative (NKF-K/DOQI) recommends incorporating a subjective
global assessment (SGA) tool for evaluation and monitoring of nutritional status in the popula-
tion with CKD 4 (National Kidney Foundation, 2000). Kalantar-Zadeh et al. (2001) developed
the Malnutrition Inflammation Complex Syndrome subjective global assessment (MICS SGA) to
capture the unique factors associated with malnutrition in predicting morbidity and mortality out-
comes in the population with ESRD (Kalantar-Zadeh et al., 2001). This tool combines elements
of the conventional SGA with indicators such as BMI, serum albumin, and total iron-binding
capacity. It was recently found that morbidity and mortality in patients on renal transplant can be
predicted using the tool, and hence the tool should be considered for use in patients with CKD 4
(Molnar et al., 2010).
Nutrition for Chronic Kidney Disease, Stage 4 125
Tools such as diet recall, food frequency questionnaires, or food diaries can all be utilized to
obtain a food- and nutrition-related history but should be geared to renal-specific food groups for
assessment of intake of potassium, phosphorus, and protein. Online interactive tools are becom-
ing more prevalent and can be used to complete the assessment from patients home or office
before their medical appointment. In addition, access to appropriate foods should be assessed and
taken into account when developing diet recommendations. K/DOQI also recommends inclu-
sion of normalized protein nitrogen appearance when assessing dietary intake (National Kidney
Foundation, 2000).
The American Dietetic Association (ADA) recently published evidence-based guidelines for
CKD, which summarize well the components of a comprehensive assessment. They recommend
evaluating not only the nutritional status and evidence of protein-energy malnutrition but also
dietary factors related to glycemic control, inflammation, electrolyte disorders, mineral and bone
disorders, anemia, dyslipidemia, and, of course, kidney function (ADA, 2010). This approach takes
into account the complexity of CKD 4 in patients and the need to minimize the effect of comorbidi-
ties and uremic toxins on the kidneys while promoting optimal nutrition.
Assessment and monitoring of renal-specific lab values is essential for appropriate management
of patients with CKD 4. K/DOQI Clinical Practice Guidelines for Nutrition in Chronic Renal
Failure were published in 2000 and provide specific recommendations for laboratory value targets.
Care must be taken when interpreting lab values in patients with CKD 4. Serum albumin is the
preferred measurement for visceral protein stores and is found to be predictive of increased risk
of mortality in patients with ESRD (National Kidney Foundation, 2000). However, in the popula-
tion with renal diseases, serum albumin levels are often confounded by fluid status (edema) and
chronic inflammation (Fuhrman et al., 2004; Kalantar-Zadeh et al., 2003). Albumin is a negative
acute-phase protein that decreases during illness or trauma. In addition, systemic inflammation
caused by cytokines and other mediators significantly decreases hepatic proteins such as albumin
and prealbumin. This relationship necessitates that in patients with CKD 4, hepatic proteins, spe-
cifically albumin, are more appropriately viewed as a prognostic indicator versus a biomarker for
nutritional status (Fuhrman et al., 2004). Albumin can be very useful in predicting the severity of
the illness and the outcomes in CKD. Consequently, serum albumin alone should not be used to
determine the nutritional status but should be used in conjunction with other elements for a com-
prehensive nutritional assessment.
9.4 N
UTRITIONAL RECOMMENDATIONS FOR PATIENTS
WITH CKD 4MACRONUTRIENTS
9.4.1 Protein
K/DOQI Clinical Practice Guidelines for Nutrition in Chronic Renal Failure has become the stan-
dard of care for most providers and addresses both macro-and micronutrient needs for patients
with CKD. Determining the recommendations for appropriate protein intake for patients with CKD
4 remains the most controversial aspect of care. K/DOQI recommends a low-protein diet (LPD)
providing 0.60 g/kg/day for nondialyzed patients with a GFR of <25 mL/min (National Kidney
Foundation, 2000). It also recommends a protein level of 0.75 g/kg/day for those patients who are
not willing to follow an LPD or are unable to sustain adequate total energy intake on an LPD.
LPDs have been one of the primary interventions initiated for decreasing the workload on the
kidneys while reducing uremia and its effects on the rest of the body. Decrease in the intake of
phosphorus, potassium, and sodium tends to occur with an LPD, leading to improvements in many
of the complications of kidney failure. However, debate remains on the safety of restricting protein
intake in patients who are already at the risk of malnutrition. Studies exploring the long-term risks
and benefits of an LPD have yielded mixed results. Shortfalls in many of the studies include poor
assessment of adherence to prescribed protein intake levels, limited long-term follow-up, and the
126 Nutrition Therapy for Chronic Kidney Disease
exclusion of diabetics (Eyre et al., 2008). It should be noted that a spontaneous decrease in protein
intake is associated with an eGFR of <25 mL/min secondary to taste changes and GI issues (Ikizler,
2009).
A 2007 Cochrane review looked at protein restriction for diabetics with renal disease and found
only small improvements in renal function with protein-restricted diets (Robertson et al., 2007).
Interestingly, this review found that the actual protein intake ranged from 0.7 to 1.1 g/kg/day.
Cianciaruso et al. (2008) found that in over 400 patients, LPD improved metabolic control without
an increased risk of malnutrition (Cianciaruso). In a follow-up study, they concluded that an LPD was
not significantly more effective than a moderate-protein diet (0.8 g/kg/day) in decreasing the risk of
death or initiation of RRT, and therefore they believe that it has secondary effects on metabolic factors
(Cianciaruso et al., 2009). The Modification of Diet in Renal Disease study is considered the definitive
study to date on the effect of dietary modifications on CKD outcomes. The study group performed a
long-term follow-up of participants in Study B [LPD vs. VLPD (very low protein diet) = 0.28 mg/kg/
day plus keto/amino acid supplementation] and concluded that a VLPD had no significant effect on
delaying progression of kidney failure but increased the risk of death on long-term use, particularly
in those starting dialysis (Menon et al., 2009). Given that restricting protein intake has the potential
to preserve renal function and reduce the symptoms of uremia with minimal impact on nutritional
status, many feel that this recommendation should be utilized more frequently with close monitoring
by a dietitian. Critics believe that the minimal effect of delaying disease progression is far outweighed
by the potential for malnutrition and suggest that the focus should be on less risky methods to slow
disease progression than on protein restriction (Eyre and Attman, 2008; Kasiski etal., 1998).
While efficacy of the LPD remains questionable, adherence to the diet is a key factor to be
considered. Proponents of the LPD emphasize the need to assess a patients ability to adhere to the
recommendations as necessary for the effectiveness of the LPD. Designing a palatable LPD is nec-
essary to promote adherence of the LPD and requires the professional skills of a registered dietitian
(RD). Close monitoring is also essential to ensure that the patient does not develop protein-energy
malnutrition. Some experts recommend a trial period of 6 months to determine whether use of LPD
is an effective strategy for individual patients (Robertson et al., 2007).
The protein source, animal versus vegetable, has also received consideration when determining
protein recommendations. There exists a persistent belief that red meat in high amounts accelerates
renal failure. A recent review concluded that the absolute amount of protein intake, no matter the
source, was associated with renal injury in healthy people and with progression of renal failure in
those with CKD (Bersnstein et al., 2007). However, for persons with diabetes, evidence suggests
that substituting vegetable or fish protein for animal protein may decrease the amount of protein in
the urine. Further study is needed, in this very important area, to make conclusive recommenda-
tions, and therefore, the final effective amount of protein intake will need to be based on individual
patients and their goals as well as response to medical nutrition therapy (MNT).
9.4.2 Energy
Adequate dietary energy intake is essential to support lower protein recommendations and optimize
amino acid utilization. According to K/DOQI Guidelines, an intake of 35 kcal/kg/day is required
to maintain nitrogen balance, as well as albumin levels, and weight in nondialyzed patients with a
GFR <25 mL/min (National Kidney Foundation, 2000). Patients >60 years or more may require
less (30 kcal/kg/day) calories based on lower activity levels. The ADA provides further guidance
in its CKD Evidence-Based Guidelines and recommends a range of 2235 kcal/kg/day factoring in
weight status and goals, age, gender, activity level, and other metabolic stressors of patients, such as
comorbidities, surgery, or infections (ADA, 2010).
The key to determining the appropriate, individualized recommendation for protein and energy
intake rests on the estimated body weight used for the calculations. Actual body weight can reflect
fluid overload in the nondialyzed patient and lead to overestimating needs and potential weight
Nutrition for Chronic Kidney Disease, Stage 4 127
gain.Determining the edema-free weight in patients with CKD 4 can be challenging and often neces-
sitates the clinician to use an estimated or desired body weight based on height and weight history.
K/DOQI recommends using a standard body weight (SBW) based on National Health and Nutrition
Survey (NHANES) II data for age, height, gender, and frame size or an adjusted weight for those who
fall below 95% of the SBW or above 115% of the SBW (National Kidney Foundation, 2000). Both
under- and overestimation of needs can be detrimental to the patients with CKD 4. Frequent monitoring
of adherence to intake recommendations and of the changes in weight and nutritional status is neces-
sary to determine the appropriateness of the recommendations regardless of what method is used. It
should also be noted that weight loss might be a necessary goal for patients with CKD 4 to improve
overall health, blood pressure, and glycemic control. This goal must be balanced against the risks of
malnutrition inherent in restricting both protein and total calories and requires close monitoring by both
the physician and the dietitian.
9.5 N
UTRITIONAL RECOMMENDATIONS FOR PATIENTS
WITH CKD 4MICRONUTRIENTS
9.5.1 Bone Metabolism and Phosphorus
Phosphorus is an essential mineral for bone structure and a number of physiological processes in
the body. Phosphorus is absorbed through the intestines, with the aid of active vitamin D, and is
excreted via the kidneys. Consequently, as GFR declines and kidney failure progresses, phosphorus
levels in the blood begin to rise. However, owing to the ability of the kidneys to adapt to an increase
in phosphorus levels and an increase in PTH and fibroblast growth factor-23, overt hyperphosphate-
mia does not occur until the onset of CKD 4 (Burke, 2008). It is well established that uncontrolled,
chronic high-phosphorus levels contribute to hyperparathyroidism that leads to high-turnover
bone disease, promotes vascular calcification, and is associated with increased all-cause mortality
(Burke, 2008). The increased incidence of CVD seen in the population with CKD is believed to be
related to the arterial calcification mediated by high phosphorus. Hyperphosphatemia is considered
an independent risk factor for morbidity and mortality in renal failure (Block et al., 2004). Early and
adequate phosphorus control may have long-term implications.
The interplay of phosphorus, calcium, and PTH is very complex as kidney function declines, with
common practice standards in the predialysis population focused on addressing the lab values of
phosphorus, calcium, and PTH only as they become out of range. Current recommendations, how-
ever, suggest preventing high phosphorus levels in patients with CKD 4 by limiting dietary phos-
phorus intake to 8001000 mg/day or 1012 mg/g of protein intake (National Kidney Foundation,
2003; Sigrist et al., 2009). Following an LPD supports this recommendation as most phosphorus
comes from protein and dairy sources. Using the protein recommendation guideline as a basis for
phosphorus intake minimizes phosphorus sources that have minimal protein content. This is an
important consideration when seeking to minimize the risk of malnutrition by overrestricting the
diet. As the GFR reaches 15 mL/min, dietary control will often not be adequate to prevent hyper-
phosphatemia, and phosphate-binding medications may be necessary. Binders may also be a useful
tool for patients for whom an LPD is inappropriate.
Dairy products, animal protein, and nuts in the diet have historically been the primary sources
of phosphorus, which have been addressed in the diet for patients with CKD. However, phosphorus-
containing food additives are frequently being used in food production. They are found in beverages
as a stabilizer or in meat products as a preservative and for color enhancement (Murphy-Gutekunst,
2007). Often this additional phosphorus is not captured on food labels, and therefore it is difficult
to identify this. In addition, this inorganic phosphorus appears to be more easily absorbed and is
estimated to contribute an additional 1000 mg/day of phosphorus in the diet (Uribarri and Calvo,
2003). With ongoing education on these facts, these significant sources of hidden phosphorus must
be taken into account for adequate management of phosphorus.
128 Nutrition Therapy for Chronic Kidney Disease
potassium levels. Other causes of hyperkalemia include uncontrolled diabetes, acidosis, tissue
breakdown, and chronic constipation (National Kidney Foundation, 2009). Incidence of hyperkale-
mia increases in patients with CKD 4; however, it is important to determine the contributing factors
before limiting the dietary intake of potassium immediately and further restricting the diet. Intake
recommendation for dietary potassium in patients with CKD 4 is <2.4 g/day if they have hyperkale-
mia. Lower protein intake will support this intake level, but paying attention to intake of fruits and
vegetables that are considered high sources of potassium, such as tropical fruits or potatoes, is also
important. Reading of food labels is also an important tool, as sodium is increasingly being replaced
with potassium in many low-sodium canned and prepackaged foods. Education on appropriate low-
sodium alternatives that do not use additional potassium is increasingly necessary for recommenda-
tion of appropriate diet to patients with CKD 4.
9.7.1 Vitamin D
The body stores vitamin D as 25-OH vitamin D, which must then be activated by the kidney to form
1, 25 OH vitamin D or active vitamin D. Patients with CKD are at increased risk of vitamin D defi-
ciency, which is defined as <30 ng/mL, as a result of limiting dietary phosphorus, chronic illness,
age, and renal failure. K/DOQI recommends treating vitamin D deficiency to maintain adequate
levels of 25-OH vitamin D (Cuppari and Garcia-Lopes, 2009). Treatment recommendations vary
from aggressive treatment of 50,000 IU of ergocalciferol weekly, until levels are >30 ng/mL, to a
moderate daily dose of 10002000 IU of cholecalciferol (Heaney et al., 2003; National Kidney
Foundation, 2003). It should be noted that the current DRI for vitamin D is 600800 IU/day with an
upper limit (UL) of 4000 IU/day (IOM, 2010). Renal-specific vitamin formulations that also contain
10002000 IU D3 are available now.
9.7.2 Anemia
Anemia is a common feature in patients with CKD 4, with estimates of >50% of patients in stages
35 suffering from anemia. As renal failure progresses, the kidney is unable to produce the hor-
mone EPO, which stimulates red blood cell production. Medical management of anemia in CKD
includes the use of recombinant human EPO. In addition, as mentioned earlier, adequate iron stores
are necessary to support this treatment. Patients who remain unresponsive to EPO with adequate
iron stores should be evaluated for vitamin B12 and folic acid deficiency and treated if needed (ADA,
2010). Many continue to recommend vitamin C to enhance the absorption of iron supplements;
however, intake of levels above the DRI should be avoided (National Kidney Foundation, 2006).
Often for patients with CKD 4, what began as one chronic illness of hypertension or diabetes
then becomes layered with additional chronic issues requiring multiple medications with concomi-
tant diet and/or lifestyle adjustments. Assisting the patients with CKD 4 in balancing priorities and
developing goals that are achievable and sustainable is a key role of the renal dietitian. Stressing to
the patients the significance of each incremental improvement in the various areas of concern may
help them keep their focus and motivation.
9.8.1 Diabetes
Adequate diabetic management can slow the progression of renal failure in patients with CKD 4.
Diet management is essential to reach and maintain good glycemic control while avoiding the risks
of hypoglycemia. K/DOQI recommends achieving a hemoglobin A1c of <7% or an estimate aver-
age glucose of <154 mg/dL to preserve renal function and slow down diabetes-related nephropathy
(NKF, 2007). For insulin-dependent diabetics, the risks of hypoglycemia increase as renal failure
progresses, and the kidney is less able to clear insulin that then remains longer in the blood stream.
Increasing GI issues and poor dietary intake also contribute to more frequent hypoglycemic epi-
sodes. Education on renal-specific foods to address hypoglycemia, such as apple juice instead of
orange juice, must be included. Often the diet becomes overwhelming for diabetic patients with
CKD 4, who must learn to balance carbohydrate, fat, and protein intake while restricting sodium
and potassium. RDs who are knowledgeable in renal-specific diet can help the patient with CKD 4
manage this complex diet.
9.8.3 Obesity
Obesity and weight management must also be addressed in patients with CKD 4. Obesity plays
a critical role in the development and management of diabetes and hypertension as well as CVD.
Obesity is also believed to predispose people to renal failure and is an independent risk factor for
graft failure and death in posttransplant stage in patients (Kopple, 2010; Meier-Kriesche et al.,
2002). However, the goals of weight management must be constantly balanced against preventing
protein-energy malnutrition in this at-risk group. As mentioned earlier, LPDs must be supported
by adequate energy intake. Therefore, the typical strategy of reduced or low-calorie diets may not
be appropriate for patients with CKD 4. Diets that are considered effective in the healthy popula-
tion, such as low-carbohydrate diets (<35% calories from carbohydrates) or diets high in dairy
foods, should be avoided as they often have higher levels of protein, phosphorus, and calcium than
Nutrition for Chronic Kidney Disease, Stage 4 131
that recommended for CKD 4. Research on safe and effective diets for those with CKD is limited.
However, a patient who is focused on a high-quality diet that promotes good diabetic and blood
pressure control as well as cardiovascular health will likely result in maintaining his/her weight and
possibly promoting slow weight loss.
Encouraging increased physical activity (within the physical limitations of the patient) may be
an effective tool of weight management in patients with CKD 4, as it also promotes maintenance
of lean body mass and improves overall cardiovascular health (ADA, 2010). In addition, physical
activity has been shown to improve diabetic control and renal function (Straznicky et al., 2011).
The American Diabetes Association and the American College of Sports Medicine have recently
released their joint position statement on exercise and type 2 diabetes. They recommend 150 min of
moderately vigorous aerobic activity weekly plus 23 sessions of resistance training (Colberg et al.,
2010). ADA guidelines on adult weight management also recommend the use of multiple behavior
strategies for effective weight loss. They include self-monitoring, stress management, stimulus con-
trol, problem solving, contingency management, cognitive restructuring, and social support (ADA,
2006). Beyond weight management, these strategies will be necessary for patients with CKD 4 and
should be incorporated into the comprehensive plan of care for those patients.
Strategies for improving adherence are also addressed in diabetes and hypertension man-
agement in the KDOQ/I guidelines. K/DOQI guidelines emphasize, in the Clinical Practice
Recommendations for Diabetics and CKD published in 2007, that effective strategies to effectively
manage both diabetes and CKD depend on adequate self-management skills (NKF, 2007). They
list six strategies that they believe should comprise the treatment plan for patients with diabetic
CKD and that, except for glycemic control, are applicable to all patients with CKD 4. The strategies
include the following: monitoring and treatment of blood glucose, blood pressure, nutrition, smok-
ing cessation, exercise, and adherence to medications (NKF, 2007).
Assessment of the patients ability to adhere to diet and lifestyle recommendations must be done to
identify and address potential barriers. The dietitian can provide tools for establishing goals, tracking
progress, and problem solving, which can assist patients in managing their complex needs. K/DOQI
also stresses the need for education and treatment plans to be culturally and economically sensitive
as well as geared to the learning level of the patient. Engaging the support of the family can also be
useful when a patient must make significant changes to his diet and lifestyle. A focus on establishing
good self-management skills and habits can clearly have an impact on all aspects of care for patients
with CKD 4. We must recognize patients with CKD as the central players in the management of their
health status and must focus on developing their problem-solving skills so as to address their barriers
to adherence of diet/medications and avoid reliance on information-only education.
9.10 EDUCATION
Utilizing multiple strategies to improve adherence is essential for successful management of patients
with CKD 4. Although education alone is not sufficient, well-designed educational pieces that are
132 Nutrition Therapy for Chronic Kidney Disease
patient-specific are a valuable tool for the dietitian. The Internet is a tool that has not been fully
utilized. To date, there is limited research on the effectiveness of Web-based nutrition interventions
for CKD, diabetes, or hypertension. A review of Web-based weight-loss interventions found those
that were dynamic, individualized the process, and utilized self-monitoring tools were more effec-
tive and had greater retention (Arem et al., 2010). Currently, large dialysis centers offer such tools
free of charge for patients with CKD. However, not all patients have access to the Internet on a daily
basis. Effective education pieces should address the amount of sodium, potassium, and phosphorus
in basic foods as well include information on reading of food labels to determine the nutrient content
of purchased foods. In addition, education that combines components of diabetes management with
the above provides patients with a resource that they can apply to their daily life.
9.11 SUMMARY
Nutrition management of patients with CKD 4 requires ongoing collaboration with the patient and the
multidisciplinary team to successfully address all the concurrent contributing factors. Nutrition and
diet play a key role as many symptoms and disease outcomes are related to dietary intake and can be
managed with appropriate adjustments. The comprehensive assessment of patients with CKD 4 should
include the following: diet and medication history, knowledge about their disease, behavior and life-
style assessment, and an understanding about socioeconomic factors that may influence adherence to
recommendations. Early and accurate assessment of macro- and micronutrient intake is essential for
managing the symptoms related to CKD 4 as well as for slowing down the progression of the disease
(Table 9.1). Understanding the role of diet in management of the comorbidities associated with CKD 4
assists in the effectiveness of the medications used to manage both diabetes and hypertension (Grundy
et al., 2001; Mitch, 2005). In addition to medical management, behavior and lifestyle changes in
weight management, physical activity level, and smoking cessation are needed to support these goals.
TABLE 9.1
Macro and Micronutrient Goals for Patients with CKD 4
Nutrient Diabetic Nondiabetic
Energy 2235 kcal/kg 2235 kcal/kg
Protein 0.81.0 g/kg 0.60.8 g/kg
Total fat 25%35% of total calories Only if dyslipidemia
Saturated and trans fat <7% of calories and/or cardiovascular
disease
Cholesterol <200 mg/day
Phosphorus 800100 mg/day (1012 mg/g protein)
Calcium <2000 mg/day includes all sources
Potassium <2400 mg if elevated
Sodium 15002300 mg/day (lower end optimal)
Renal multivitamin
intravenous infusion (MVI)
Data combined from sources: USDA, Dietary Guidelines for Americans. Dietary
Guidelines.gov. Online: www.cnpp.usda.gov/DGAs2010-DGACReport.htm
(accessed September 12, 2010); ADA (American Dietetic Association Evidence
Library), Chronic Kidney Disease Evidence-Based Nutrition Practice
Guideline, 2010. Online: www.adaevidencelibrary.com/topic.cfm?cat=3927
(accessed September 27, 2010); National Kidney Foundation, Pocket Guide to
Nutrition Assessment of the Patient with Chronic Kidney Disease, 4th ed.,
National Kidney Foundation, New York, 2009.
Nutrition for Chronic Kidney Disease, Stage 4 133
However, adherence to behavior and lifestyle changes is particularly challenging for patients
with CKD 4 owing to both the complexity and the uniqueness of the diet. The renal dietitian has the
opportunity to bring all aspects of disease management together and assist patients in developing
strategies to meet their individual goals. The renal dietitian also plays an important role in coordi-
nating care with the various practitioners who comprise the interdisciplinary team for patients with
CKD 4. Communicating with the nephrologist on MNT plans and progress can provide an addi-
tional layer of reinforcement and accountability for the patient, thereby increasing the likelihood
of success of management of CKD. Ultimately, adequate management of CKD 4 will be measured
based on the ability to delay the need for RRT and on the nutritional status of patients with CKD 4
when they reach ESRD.
Finally, practice guidelines and standards of care are changing rapidly as organizations such
as the National Kidney Foundation continue to evaluate current research on CKD, with frequent
updates to the KDOQ/I guidelines. The ADA Evidence Analysis Library produces evidence-based
nutrition practice guidelines for specific health problems. Their recently published guideline on CKD
is a valuable resource with many useful tools for developing a comprehensive plan for nutrition inter-
vention as well as monitoring and evaluation. It is essential that the dietitians providing MNT to the
patient with CKD stay informed. Fortunately, there are multiple tools available to assist them. The
following list includes resources that should be checked frequently for the latest recommendations:
REFERENCES
ADA. (American Dietetic Association Evidence Library). 2006. Recommendations Summary Adult Weight
Management: Multiple Behavior Therapy Strategies. May. Online: www.adaevidencelibrary.com/tem-
plate.cfm?template=guide_summary&key=628 (accessed November 27, 2010).
ADA. (American Dietetic Association Evidence Library). 2010. Chronic Kidney Disease Evidence-Based Nutrition
Practice Guideline. Online: www.adaevidencelibrary.com/topic.cfm?cat=3927 (accessed September 27,
2010).
Arem, H., and Irwin, M. 2010. Obesity management: A review of web-based weight loss interventions in
adults. Obes Rev., August.
Bersnstein, A.,Treyzon, L., Zhaoping, L. 2007. Are high-protein vegetable-based diets safe for kidney func-
tion? A review of the literature. J Am Diet Assoc. 107 644650.
Beto, J., and Bansal, V. 2004. Medical nutrition therapy in chronic kidney failure: Integrating clinical practice
guidelines. J Am Diet Assoc. 104:404409.
Block, G., Klassen, P., Lazarus, J., et al. 2004. Mineral metabolism, mortality, and morbidity in maintenance
hemodialysis. J Am Soc Nephrol. 15: 22082218.
Burke, S. 2008. Phosphate is a uremic toxin. J Ren Nutr. 18(no. 1): 2732.
Cianciaruso, B., Pota, A., Pisani, A., et al. 2008. Metabolic effects of two low protein diets in chronic kidney
disease stage 45A randomized controlled trial. Nehprol Dial Transplant. 23: 636644.
Cianciaruso, B., Pota, A., Bellizzi, V., et al. 2009. Effect of low-versus moderate-protein diet on progression of
CKD: Follow-up of a randomized controlled trial. Am J Kidney Dis. 54: (no. 61) 10521061.
Colberg, S., Sigal, R.J., Fernhall, B., et al. 2010. Exercise and type 2 diabetes: The American College of Sports
Medicine and the American Diabetes Association: Joint position statement. Diabetes Care. 33:(no. 12)
147167.
Cuppari, L., and Garcia-Lopes, M. 2009. Hypovitaminosis D in chronic kidney disease patients: Prevalence and
treatment. J Ren Nutr. 19:(no. 1) 3843.
Eyre, S., and Attman, P. 2008. Protein restriction and body composition in renal disease. J Ren Nutr. 18 (2):
167186.
134 Nutrition Therapy for Chronic Kidney Disease
Eyre, S., Attman, P., Haraldsson, B. 2008. Positive effects of protein restriction in patients with chronic kidney
disease. J Ren Nutr. 18: (no. 3) 269280.
Fuhrman, M., Charney, P., Mueller, C. 2004. Hepatic proteins and nutrition assessment. J Am Diet Assoc. 104:
(no. 8): 12581264.
Grundy, S., Becker, D., Clark, L., et al. 2001. Executive summary of the Third report of the NCEP expert panel
on detection, evaluation, and treatment of high blood cholesterol in adults. JAMA. 285: 24882497.
Heaney, R., Davies, K., Chen, T., et al. 2003. Human serum 25-hydroxycholecalciferol response to extended
oral dosing with cholecalciferol. Am J Clin Nutr. 77: (no. 1) 204210.
Ikizler, T. 2009. Dietary protein restriction in CKD: The debate continues. Am J Kidney Dis. 53: (no. 2) 20817.
IOM. 2010. Dietary reference intakes for calcium and vitamin D. Institute of Medicine Report at a Glance.
Online: www.iom.edu/Reports/2010/Dietarty-Reference-Intakes (accessed December 10, 2010).
Kalantar-Zadeh, K., Kopple, J., Block, G., et al. 2001. A malnutrition-inflammation score is correlated with
morbidity and mortality in maintenance hemodialysis patients. Am J Kidney Dis. 38: (no. 6) 12511263.
Kalantar-Zadeh, K., Stenvinkel, P., Pillon, L., et al. 2003. Inflammation and nutrition in renal insufficiency. Adv
Ren Replace Ther. 10: (no. 3) 155169.
Kasiski, B., Lakatua, J., Ma, J., et al. 1998. A meta-analysis of the effects of dietary protein restriction on the
rate of decline in renal function. Am J Kidney Dis. 31: (no. 6) 954961.
Kopple, J. 2010. Obesity and chronic kidney disease. J Ren Nutr. 20: (no. 5S) S29S30.
Meier-Kriesche, H., Arndorfer, J., Kaplan, B. 2002. The impact of body mass index on renal transplant out-
comes: A significant risk factor for graft failure and patient death. Transplantation. 73:7078.
Menon, V., Kopple, J., Wang, X., et al. 2009. Effect of a very low-protein diet on outcomes: Long-term follow-
up of the Modification of Diet in Renal Disease (MDRD) Study. Am J Kidney Dis. 53: 208217.
Mitch, W. 2005. Beneficial responses to modified diets in treating patients with chronic kidney disease. Kidney
Int Suppl. 94: S133S135.
Molnar, M., Keszei, A., Czira, M., et al. 2010. Evaluation of the malnutrition-inflammation score in kidney
transplant recipients. Am J Kidney Dis. 56: (no. 1) 102111.
Murphy-Gutekunst, L. 2007. Hidden phosphorus: Where do we go from here? J Ren Nutr. 17: e31e36.
National Kidney Foundation. 2000. K/DOQI nutrition guidelines in chronic renal failure. Am J Kidney Dis. 35:
(no. 6) S56S63.
National Kidney Foundation. 2003. K/DOQI clinical practice guidelines for bone metabolism and disease in
chronic kidney disease. Am J Kidney Dis. 42: (no. 4) S1-S201.
National Kidney Foundation. 2006. K/DOQI clinical practice guidelines and clinical practice recommendations
for anemia in chronic kidney disease. NKF KDOQ/I Guidelines. Online: www.kidney.org/professionals/
KDOQI/guidelines_anemia/index.htm (accessed Nov 14, 2010).
National Kidney Foundation. 2007. Clinical practice guidelines and clinical practice recommendations for
diabetes and chronic kidney disease. NKF KDOQI Guidelines. Online: www.eatright.org/kdoqi/guide-
line_diabetes (accessed October 15, 2010).
National Kidney Foundation. 2009. Pocket Guide to Nutrition Assessment of the Patient with Chronic Kidney
Disease. 4th. ed. New York: National Kidney Foundation.
Robertson, L., Waugh, N., Robertson, A. 2007. Protein restriction for diabetic renal disease. Cochrane Database
Syst Rev 4.
Sigrist, M., Chiarelli, G., Lim, L., et al. 2009. Early initiation of phosphate lowering dietary therapy in non-
dialysis chronic kidney disease: A critical review. J Ren Care. 35: Suppl 7178.
Straznicky, N., Grima, M.T., Lambert, E.A., et al. 2011. Exercise augments weight loss induced improvement
in renal function in obese metabolic syndrome individuals. J Hypertens. 29: (no. 3) 553564.
U.S. Renal Data System. 2010. USRDS 2010 Annual Data Report: Atlas of Chronic Kidney Disease and End-
Stage Renal Disease in the United States. Bethesda, MD: National Institute of Health, National Institute
of Diabetes and Digestive and Kidney Diseases.
Uribarri, J. and Calvo, M. 2003. Hidden sources of phosphorus in the typical American diet: Does it matter in
nephrology? Semin Dial. 16(no. 3): 186188.
USDA. 2010. Dietary Guidelines for Americans. Dietary Guidelines.gov. June. Online: www.cnpp.usda.gov/
DGAs2010-DGACReport.htm (accessed September 12, 2010).
10 Nutrition for Chronic
Kidney Disease, Stage 5
Lesley McPhatter
University of Virginia
CONTENTS
10.1 Introduction........................................................................................................................... 135
10.2 Dialysis Treatment Options and Adequacy Measurements................................................... 136
10.3 Diet Prescription: Energy and Protein................................................................................... 137
10.4 Diet Prescription: Fluids, Sodium, and Potassium................................................................ 138
10.5 Vitamins and Minerals.......................................................................................................... 141
10.6 Special Considerations.......................................................................................................... 143
10.6.1 Cardiovascular Disease............................................................................................. 143
10.6.2 Dialysis Patients with HIV/AIDS.............................................................................. 144
10.6.3 Older Adults with CKD............................................................................................. 145
10.6.4 Disaster Planning and Emergency Diet..................................................................... 146
10.7 Summary............................................................................................................................... 146
References....................................................................................................................................... 147
10.1 INTRODUCTION
Just as nutrition is a cornerstone of treatment for many diseases, including diabetes and obesity,
diet is paramount in the treatment of all stages of chronic kidney disease (CKD). When the
glomerular filtration rate is 10% or less than the normal rate (90120 mL/min/1.73m 2), a patient
is considered to be in end-stage renal disease (ESRD; KDOQI Guidelines, 2002). Dialysis is
needed to replace diminished kidney function. Some patients in end-stage renal failure receive
kidney transplants. This restores kidney function, and the patient is able to return to a more nor-
mal diet (Figure 10.1).
The diet for dialysis patients is complicated, multifaceted, and must be individualized to each
patients needs. Maximizing intake with adequate protein and calories while limiting fluid, sodium,
potassium, and phosphorus for a chronic disease requires diligence and a patient-centered team
approach for the best overall patient outcome.
Mortality rates for patients with CKD on dialysis (CKDStage 5) in the United States are
higher than the general population. Among dialysis patients aged 2044 and 4564, mortality rates
in 2008 reached 83 and 174 deaths per 1000 patient years, respectivelyboth figures are eight times
greater than those seen in the general population. Rates among transplant patients are closest to
those of non-ESRD patients, ranging from 1.2 times greater in those aged 2044 to 1.6 times higher
among the patients above 65 years of age (USRDS, 2010).
Malnutrition affects 40%70% of all dialysis patients and significantly increases mortality
risk. There are many reasons for these alarming malnutrition statistics in dialysis patients. These
include the complications from kidney failure: uremia, fatigue, weakness, nausea, and vomiting.
Studies also show that patients do not eat secondary to poor appetite, dietary monotony, and lack of
physical/financial support (Sundell, 2007). Complications from various comorbid conditions such
135
136 Nutrition Therapy for Chronic Kidney Disease
Renal failure
Dialysis Fluid
technique overload
Circulating
endotoxins
Protective
effect?
Hyperlipidemia Obesity
Food intake
FIGURE 10.1 Schematic representation of the pathophysiology of kidney disease wasting in maintenance
hemodialysis patients. (Reproduced from Kalantar-Zadeh, K. and Balakrishnan, V, Hemodial Int., 10, 315
325, 2006. With permission from Blackwell Publishing.)
as diabetes mellitus and cardiovascular disease also affect dietary intake. Thirty-seven percent of
dialysis patients have diabetes mellitus, 82% have hypertension, and 63% have cardiovascular dis-
ease (USRDS, 2008).
Yet another reason for the development of malnutrition is poor intake related to inadequate dialy-
sis. Under dialyzed patients experience decreased taste acuity and anorexia resulting in insufficient
dietary energy and protein intake. In patients who are adequately dialyzed, dietary restrictions
and fluid limitations may impair oral intake. Appetite stimulants (megace, prednisone) and anti-
depressants with an appetite enhancing side effect (remeron) may be used in some settings. Use is
controversial and clinical trials predicting long-term positive outcomes are limited. Use should be
monitored closely and dosing should be adjusted and tapered carefully to avoid negative side effects.
prescribed artificial kidney called the dialyzer. The composition range of the dialysis bath is out-
lined as follows:
Variations depend on the facility standard, individual patient parameters, and tolerance for the
dialysis treatment. Machine choice is facility preference, but machines have a variety of specifics to
maximize the treatment for that patient with the best BFR, DFR, adjustments for bicarbonate and
sodium parameters, and the ability to monitor achievement of the adequacy goals for that patient
throughout the treatment. The artificial kidney or dialyzer is chosen based on patients needs and
biocompatibility parameters (Locatelli et al., 2004; Palmer, 2001).
Dialysis adequacy is calculated using the urea reduction ratio, which determines the decrease
in blood urea over the course of the treatment. Pre- and post-dialysis-treatment blood samples of
blood urea nitrogen (BUN) are drawn, and the following formula is used to calculate the results:
(Pre BUN post BUN)/pre BUN 100.
A goal of 65% is the current objective for CHD. In 2011, the Centers for Medicare and Medicaid
Services (CMS) began to require facilities to achieve this goal in at least 96% of their patients
who dialyze in the clinic. Most CHD patients should reach this goal after their first 6 months on
dialysis (Federal Register, 2008). Eventually, all dialysis patients adequacy will be evaluated using
the KT/V, a more complex measure of adequacy that includes an residual renal function and is an
adequacy marker that is calculated for PD. The goal for KT/V is >1.2.
within the higher limit of normal range (KDOQI, 2000). Since 2008, the CMS has recommended a
goal albumin for all dialysis patients of 4 g/dL. Amino acid losses are estimated at 812 g per CHD
treatment (Federal Register, 2008). Tables 10.1 and 10.2 contain summary energy and nutrient data
for hemodialysis and PD.
TABLE 10.1
Daily Nutrient and Fluid Needs for Adults
Undergoing Conventional Hemodialysis
Nutrients Recommendations
Energy 3035 kcal/kg
Protein 1.2 g/kg
Sodium 15002400 g
Potassium 23 g
Fluids Urine output plus 1000 mL
Calcium 2 g including binder load
Phosphorus 1012 mg/g/protein
Ascorbic acid 60100 mg
Pyridoxine 510 mg
B12 3 g
Folic acid 15 mg
No A or K
Zinc 15 mg
Riboflavin 1.82.0 mg
Niacin 20 mg
Thiamin 1.52.0 mg
Biotin 2030 g
Vitamin E 1015 IU
Pantothenic acid 10 mg
Iron Individualized
Active vitamin D As needed to treat mineral bone
disorder (MBD)
Nutritional vitamin D Replete to normal lab value for D3
Nutrition for Chronic Kidney Disease, Stage 5 139
TABLE 10.2
Daily Nutrient and Fluid Needs for
Adults Undergoing Peritoneal Dialysis
Nutrient Recommendations
Energy a 3035 kcal/kg
Protein 1.21.3 g/kg
Sodium 15002400 g
Potassium 34 g
Fluids As tolerated
Calcium 2 g including
binder load
Phosphorus 1012 mg/g/protein
Ascorbic acid 60100 mg
Pyridoxine 510 mg
B12 3 g
Folic acid 15 mg
No A or K
Zinc 15 mg
Riboflavin 1.82.0 mg
Niacin 20 mg
Thiamin 1.52.0 mg
Biotin 2030 g
Vitamin E 1015 IU
Pantothenic acid 10 mg
Iron Individualized
Active vitamin D As needed to treat
MBD
Nutritional vitamin D Replete to normal lab
value for D3
is not always necessary to restrict fluid intake unless it exceeds the maximum that can be removed
during the treatment regimen.
Sodium restriction is determined by the patients fluid and hypertensive state. Hypotensive
patients may benefit from additional dietary sodium, and normotensive patients may need only a
healthy dietary limitation of 2400 mg/day (KDOQI, 2000). The 2010 U.S. Dietary Reference Intake
guidelines recommend further limiting Na to <1500 mg/day for people with chronic diseases such
as diabetes, hypertension, and kidney disease (IOM, 2010). The feasibility of this and the long-term
benefit for CKD Stage 5 patients will require further study. Convenience foods, table salt, fast foods,
enhanced meats, canned vegetables, and other highly processed foods are the greatest sources of
sodium for dialysis patients.
Potassium (K) intake for patients on CHD is usually restricted to 23 g/day. Patients on the
more-frequent dialysis modalities may not require restriction or may only need to restrict K on their
days off dialysis. Patients with low-normal serum levels may not need to limit K. Patients who have
low potassium levels should be encouraged to increase potassium intake to avoid symptoms such as
muscle cramping.
Monthly laboratory test results can guide decisions on optimal K intake. Some patients may
need to restrict more during their longest interdialytic period and may eat more freely dur-
ing the week. The sources of hidden potassium in processed foods continue to grow as lower
140 Nutrition Therapy for Chronic Kidney Disease
sodium goals are embraced. Unfortunately, in most cases, potassium is not listed on a products
nutrition label. Patients and families should be provided with a list of the potassium content
of common foods. They should also be aware that reduced sodium products such as salt sub-
stitutes, low sodium soups, popcorn, and frozen entrees often replace sodium with potassium
chloride (KCl).
The goal for K, as noted earlier, varies with laboratory reference range values, but is typically
3.56 mEq/L for CKD patients. Hyperkalemia may present as general muscle weakness, difficult
ambulation, or bradycardia and can be life threatening; however, many patients are asymptom-
atic. Treatment goals include determining the cause of hyperkalemia. Nondietary causes include
hemolysis of lab sample, inadequate dialysis, high K concentration in dialysate, catabolism, hyper-
glycemia, insulin deficiency in diabetics, acidosis, and interactions with drugs including angioten-
sin-converting enzyme inhibitors and beta blockers. Dietary sources of high potassium are potatoes,
tomatoes, oranges, nuts, and any products containing KCl. One teaspoon of salt substitute as NOSalt
contains 664 mg potassium. See Table 10.3 for an expanded list of foods that are high in potassium
(USDA, 2011).
Potatoes and other tuberous root vegetables (e.g., yucca, batata, eddo, yampi, and yams) are a sig-
nificant part of the diet for many persons. The potassium content of these vegetables can be reduced
by double cooking. The vegetables should be peeled and sliced, covered in water, brought to a boil,
cooked 510 min, and then drained. Fresh water should be added to the cooking pot, brought to a
boil for the second time, and the vegetable cooked until it is soft and tender (Burrowes and Ramer,
2008; Figure 10.2).
TABLE 10.3
Higher Potassium Foods
Amount of
Food Portion Potassium (mg)
Baked beans 1 cup 653
Banana 1 medium 422
Beet greens 1 cup 1309
Cantaloupe 1 c pieces 427
Honeydew melon 1 c pieces 388
Lima (butter) beans cup 445
Milk, reduced fat, 2% 1 cup 366
Milk shake, chocolate 11 oz 672
Orange juice, fresh 1 cup 443
Peaches 1 medium 285
Prunes, dried, stewed cup 494
Peanuts, oil roasted cup 573
Potato with skin, baked 1 medium 751
Potato fries 10 strips 334
Raisins cup 543
Sweet potato, baked 1 medium 542
Spinach, cooked from raw cup 418
Tomato 1 medium 292
TABLE 10.4
General Vitamin and Mineral Renal Formulations
Recommended Recommended
Vitamin Amount/Day Vitamin Amount/Day
Vitamin C 60100 mg Thiamin (B1) 1.5 mg
Riboflavin (B2) 1.7 mg Niacin 20 mg (as
niacinamide)
Pyridoxine (B6) 10 mg Cobalamin (B12) 6 mcg
Folic acid 1 mg Pantothenic acid 510 mg
Biotin 150 mcg Zinc 12.5 mg
TABLE 10.5
Higher Phosphorus Foods
Amount of
Phosphorus
Food Portion (mg)
Almonds 22 133
Baked beans 1 cup 258
Black-eyed peas, frozen, boiled 1 cup 208
Bran cereal, 100% cup 344
Cheese sauce cup 278
Couscous 1 cup 294
Ice cream, chocolate 1 cup 170
Ice cream, vanilla 1 cup 138
Lima (butter) beans, boiled cup 110
Milk, 2% 1 cup 229
Peanuts, oil roasted 1 cup 572
Peanut butter, creamy smooth 2 Tbsp 115
Split peas, boiled 1 cup 194
Sunflower seeds 1 oz 322
Taco 1 large 313
Trail mix with chocolate, nuts, and seeds cup 283
Whole wheat bread 1 slice 59
Yogurt, low-fat-fruit flavor 8 oz 270
Phosphorus levels are difficult to control in ESRD through dietary restrictions only. Phosphate
binders are necessary to maintain acceptable blood serum levels. Typical binders include calcium
carbonate, calcium acetate, magnesium carbonate, lanthanum carbonate, and sevelamer carbonate.
Aluminum hydroxide is a very effective binder, but it is rarely used because of the potential for
aluminum toxicity.
Iron deficiency is a frequent concern in patients receiving dialysis. Causal factors include gastro-
intestinal loss, blood draws, bleeding at the dialysis access site, and blood collection in the hemo-
dialyzer membrane. There is also increased demand for iron during erythropoietin therapy. Some
patients are able to maintain adequate serum levels through diet and oral supplements; however, the
majority of patients require parenteral iron therapy.
Nutrition for Chronic Kidney Disease, Stage 5 143
TABLE 10.6
The National Cholesterol Education Program (2010) Uses the Following Heart
Disease Risk Classifications
Total Cholesterol mg/dL mmol/L HDLCHOL mg/dL mmol/L
Desirable < 200 < 5.2 High 60 1.6
Borderline high 200239 5.26.2 Low < 40 < 1.0
High > 240 6.2
LDLCHOL mg/dL mmol/L Triglycerides mg/dL mmol/L
Optimal < 100 < 2.6 Normal 150 1.7
Near optimal 100129 2.63.3 Borderline 150197 1.72.2
Borderline high 130159 3.44.1 High 200499 2.35.6
High 160189 4.14.9 Very high > 500 5.7
Very high 190 5.0
144 Nutrition Therapy for Chronic Kidney Disease
TABLE 10.7
American Heart Association Diet and Lifestyle Recommendations for Cardiovascular
Disease Risk Reduction
Balance kilocalorie intake and physical activity to achieve or maintain a healthy body weight.
Consume a diet rich in vegetables and fruits.
Choose whole-grain, high-fiber foods.
Consume fish at least twice per week.
Limit your intake of saturated fat to < 7% of energy, trans fat to < 1% of energy, and CHOL to < 300 mg/day.
Minimize your intake of sugary beverages and foods. Added sugar should be limited to no more than 100 kcal for
women and 150 kcal for men each day.
Choose and prepare foods with little or no salt.
If you consume alcohol (ETOH), do so in moderation.
The Dash Diet is a well researched low fat diet that is very popular for use in prevention of cardiac disease. It is
especially helpful for reduction of elevated blood pressures.
DASH Food Categories Daily Servings Based on a 2000 kcal Diet
Breads, cereals, and other grain products (three servings should be 68
whole grain)
Vegetables 45
Fruits 45
Low-fat-dairy products 23
Lean meat, seafood, and poultry 6 ozs or less
Fats and sweets limit
Nuts, seeds, and legumes 45 per week
TABLE 10.8
Therapeutic Lifestyle Diet
NCEP Guidelines for Patients
Guidelines for Adults with High CHOL
Total fat Up to 35% total calories if mostly
monounsaturated
Saturated < 7%
Cholesterol 200 mg/day
Total calories Maintain desirable weight
Soluble fiber 1025 g/day
Plant stanols/sterols 2 g/day
Physical activity As recommended
TABLE 10.9
American Heart Association Recommendations for
Lowering Elevated Blood Lipid Levels in Adults
Step 1% Total Step 2 % Total
Prudent Diet Guidelines Calories Calories
Total fat < 30 < 30
Saturated < 10 <7
Trans <1 <1
Monounsaturated 1015 1015
Polyunsaturated 10 10
Carbohydrates 5060 5060
Protein 1520 1520
Cholesterol < 300 mg/day < 200 mg/day
TABLE 10.10
Dialysis Friendly High Fiber Fruits and Vegetables
Phosphorus
Item Serving Size Fiber (g) Potassium (mg) (mg)
Apple 1 medium 3.3 148 15
Blackberries raw 1 cup 7.6 233 32
Blueberries raw 1 cup 3.5 112 17
Carrot raw 1 medium 2.0 230 25
Cauliflower boiled 1 cup 4.9 250 43
Collards boiled 1 cup 5.3 220 57
Dates dried 4 206 210 20
Frozen mixed vegetables 1 cup 8.0 308 93
boiled
Green snap beans boiled 1 cup 4.0 182 36
Peaches canned 1 cup 3.1 206 22
Pears canned 1 cup 3.9 129 17
Pineapple raw 1 cup 2.2 169 12
Raspberries frozen 1 cup 11.0 285 42
Winter squash 1 cup baked 2.2 181 22
The use of protease inhibitors and/or nucleoside reverse transcriptase inhibitors can exhibit
symptoms of fat redistribution and peripheral lipodystrophy. Clinical signs are elevated blood lip-
ids, insulin resistance, and enlarged truncal girth. A diet that avoids simple carbohydrates, is higher
in fiber and lower in saturated fats, with necessary adjustments for kidney disease, is generally
recommended (American Dietetic Association, 2010).
musculoskeletal changes that can increase the risk of inadequate nutritional status. CKD is also
known to impair taste perception.
Dry mouth, or xerostomia, is quite common in older adults, and the usual fluid restriction
required for dialysis patients serves to exacerbate the problem. Therapies can include sucking on
sugarless candy or chewing sugarless gum, using mouth sprays, avoiding tobacco and alcohol use,
and limiting salty foods. At home, the use of a humidifier can help to moisten the air. If possible,
medications that contribute to dry mouth should be changed.
Taste perception and olfaction decline with aging. Salt and sugar tastes are the last strong sensa-
tions. The older patients diet should contain some of these strong flavors to enhance appetite (NIH
Senior Health, 2011).
Poor dentition and periodontal disease also plague older adults. Five percent of seniors older than
65 years have no teeth, and 23% have untreated decay (NIDCR, 2011). Dietary modifications, such
as recommending canned fruits instead of fresh, can help increase overall food intake.
As aging reduces the pleasure of eating, anorexia and weight loss may occur. Poor intake along
with impaired digestion and absorption of nutrients leads to malnutrition.
Patient dietary education should emphasize frequent small meals and snacks. For patients with
mobility problems, approved ready-to-eat meals and easy-to-prepare recipes are very helpful.
Nutritional supplements, either canned or homemade, are an easy way to add protein and calories
to the diet.
Education materials should be in large print, sans serif type, with high contrast between the
words and background, and should be at the appropriate reading level for the patient. Patients fami-
lies and caregivers should always be included in the educational counseling experience (Thomas
etal., 2001).
10.7 SUMMARY
Maintaining proper nutrition in the dialysis patient requires a patient-centered team approach.
Socioeconomic status, mental and physical cognitive levels, and comorbid conditions all play a
role in the maintenance of a patients nutritional status. To determine the best course of action for
each patient, an individualized care plan must be established along with measurable goals as soon
as CKD is recognized. Interventions can include dietary nutritional supplementation and appe-
tite stimulants. Use of appetite stimulants is controversial and clinical trials predicting long-term
positive outcomes are limited. Use should be monitored closely and dosing should be adjusted and
tapered carefully to avoid negative side effects (Bossola et al., 2009, 2010). They can improve nutri-
tion outcomes quickly. In extreme cases of malnutrition, patients may require short- or long-term
use of intradialytic parenteral nutrition or home total parenteral nutrition. The correction of social
and/or economic barriers through assistance programs such as Meals On Wheels or home health
care providers can be beneficial. In some cases, placing the patient in assisted living or nursing
facilities will provide the best outcome. Regardless, a patient who is failing nutritionally will not
survive if not treated aggressively and correctly. Focusing on the total nutrition picture, prioritizing
goals and helping the patient and family understand the need for changes to the diet will ultimately
prove the most valuable to the dialysis patient.
Nutrition for Chronic Kidney Disease, Stage 5 147
TABLE 10.11
Emergency Shopping List for the Adult Dialysis Patient
Food stored in the refrigerator and/or freezer should be used first. Limit fluid intake as much as possible.
(Food for 23 days)
Bottled water: allow 5 gallons
(~23 L) for hygiene purposes plus usual fluid restriction
Boxed juices
Powdered milk, boxed milk, or small cans of evaporated milk
Loaf of white bread
Dry cereal: corn flakes, rice flakes, cheerios, puffed wheat and rice, or shredded wheat
Box of vanilla wafers or other plain cookies
Box of graham crackers
Box of unsalted crackers
Granulated sugar
Small jars of mayonnaise (open one each day)
Small cans/packets of canned meats and fish (open, eat, and then throw away leftovers. Do not try to save
without refrigeration)
Peanut butter
Hard candy in different flavors
Canned fruit: peaches, fruit cocktail, pears, pineapple, mandarin oranges, and applesauce
Fresh apples, lemons, carrots, if available
Jellies: apple, grape, strawberry, blueberry, blackberry
Marshmallows
Plastic dinnerware and utensils, paper towels, napkins, and a nonelectrical can opener.
REFERENCES
American Dietetic Association. 2010. Position paper: Nutrition intervention and human immunodeficiency
virus infection. J Am Diet Assoc. 110: 11051119.
American Dietetic Association. 2011. Evidence-Based Nutrition Practice Guidelines on CKD. Available at:
http://www.adaevidencelibrary.com/category.cfm (accessed July, 2011).
American Heart Association. 2010. www.heart.org, accessed July 8, 2010.
Bossola, M., Tazza, L., Luciani, G. 2009. Mechanisms and treatment of anorexia in end-stage renal disease
patients on hemodialysis. J Renal Nutr. 19(1): 29.
Bossola, M., Tazza, L., Giungi, S., et al. 2010. Artificial nutritional support in chronic hemodialysis patients:
Anarrative review. J Renal Nutr. 20(4): 213223.
Burkart, J. 2004. Metabolic consequences of peritoneal dialysis. Semin Dial. 17(6): 498504.
Burrowes, J. and Ramer, N. 2008. Changes in potassium content of different potato varieties after cooking.
JRenal Nutr. 18(6): 530534.
Federal Register. 2008. Conditions for coverage for end stage renal disease facilities interpretive guidelines,
final rule. Federal Register, 73(73),Tuesday, April 15.
Institutes of Medicine. 2010. Dietary reference intakes: Electrolytes and water. Available at: http://www.iom.
edu/Global/News%20Announcements/~/media/442A08B899F44DF9AAD083D86164C75B.ashx
Friedman, A., Boston, A., Levey, A., et al. 2002. Plasma total homocysteine levels in patients undergoing noc-
turnal versus standard hemodialysis. J Am Soc Nephrol. 13: 265268.
Kalantar-Zadeh, K. and Balakrishnan, V. 2006. The kidney disease wasting: Inflammation, oxidative stress, and
diet-gene interaction. Hemodial Int. 10: 315325.
KDIGO Guidelines for CKD Mineral bone disorder. 2009. J Int Soc Nephrol. 76: Supplement 113.
KDOQI Bone Disease Work Group. 2003. K/DOQI clinical practice guidelines for bone metabolism and dis-
ease in chronic kidney disease. Serum calcium and calciumphosphorus product. Am J Kidney Dis. 42:
S77S83.
KDOQI Clinical Practice Guidelines for Chronic Kidney Disease. 2002. Guideline 1: Definition and Stages
of Chronic Kidney Disease. National Kidney Foundation. www.kidney.org (accessed March 24, 2011).
148 Nutrition Therapy for Chronic Kidney Disease
KDOQI Nutrition Work Group. 2000. K/DOQI clinical practice guidelines for nutrition in renal failure.
Management of protein and energy intake. Am J Kidney Dis. 35:S40S45.
Kjellstrand, C. and Ing, T. 1998. Daily hemodialysisHistory and revival of superior dialysis method and
literature review. ASAIO J. 44:117122.
Kopple, J. 2010 Trace elements and vitamins. In Mitch, W. and Ikizler, T. (Eds.), Handbook of Nutrition and
the Kidney. Wolters Kluwer, Philadelphia, PA, 163176.
Locatelli, F., Covic, A., Chazot, C., et al. 2004. Optimal composition of the dialysate with emphasis on its influ-
ence on blood pressure. Nephrol Dial Transplant. April 19: 785796.
Mathes, H. 2010. Management of cardiovascular disease in patients with impaired renal function. Renal
Nutrition Forum. Summer 29(3): 68.
McCann, L. ed. 2009. Pocket Guide to Nutrition Assessment of the Patient with Chronic Kidney Disease, 4th
ed. New York: National Kidney Foundation.
Mohr, P., Nuemann, P., Franco, S., et al. 2001. The case for daily dialysis: Its impact on costs and quality of
life. Am J Kidney Dis. 37(4):777789.
National Cholesterol Education Program. 2010. http://www.nhlbi.nih.gov/guidelines/cholesterol/atglance.htm
(accessed March 29, 2011).
National Institutes of Dental and Craniofacial Research. 2011. http://www.nidcr.nih.gov/DataStatistics/
(accessed April 1, 2011).
National Institutes of Health (NIH). 2011. http://nihseniorhealth.gov/problemswithtaste/toc.html (accessed
March 31, 2011).
Palmer, B. 2001. Individualizing the dialysate for hemodialysis patients. Semin Dialysis. JanFeb 14 (1): 4149.
Pertosa, G., Grandaliano, G., Simone, S., et al. 2005. Inflammation and carnitine in hemodialysis patients.
JRenal Nutr. 15(1): 812.
Plourd, D. 1995. Nutritional management of the dialysis patient with AIDS. J Renal Nutr. 5(4): 182193.
Raj, D., Ouwendyk, M., Francoeur, R., et al. 2000. Beta 2-microglobulin kinetics in nocturnal hemodialysis.
Nephrol Dial Transpl. 15: 5864.
Sarathy, S., Sullivan, C., Leon, J., et al. 2008. Fast food, phosphorus-containing additives and the renal diet.
JRenal Nutr. 18(5): 466470.
Sullivan, J. 2010. Effect of short daily hemodialysis and nightly home hemodialysis on phosphorus status.
Renal Nutrition Forum. Summer 29(3): 15.
Sundell, M. 2007. Actual intake vs. prescribed diet in a hemodialysis population: Comparison using a two day
dietary recall. Renal Nutrition Forum. 26(3): 812.
Tabibi, H., Hakeshzadeh, F., Hedayati, M., et al. 2011. Effects of l-carnitine supplement on serum amyloid A
and vascular inflammation markers in hemodialysis patients: A randomized controlled trial. J Renal Nutr.
21(6): 485491.
Thomas, L., Michels, P., Richter, D., et al. 2001. Identification of the factors associated with compliance to
therapeutic diets in older adults with end stage renal disease. J Renal Nutr. 11(2): 8089.
USDA. 2011. Nutrient database for standard reference. http://www.nal.usda.gov/fnic/foodcomp/search
(accessed March 22, 2011).
US Renal Data System, USRDS. 2008. Diabetes and Digestive and Kidney Diseases, Bethesda, MD, 2008.
US Renal Data System, USRDS. 2010. Annual Data Report: Atlas of Chronic Kidney Disease and End-Stage
Renal Disease in the United States, National Institutes of Health, National Institute of Diabetes and
Digestive and Kidney Diseases, Bethesda, MD.
11 Nutrition for Children
and Adolescents with
Chronic Kidney Disease
Peggy Solan
Seattle Childrens Hospital
CONTENTS
11.1 Etiologies of Chronic Kidney Disease in Children.............................................................. 149
11.2 Epidemiology of CKD in Children....................................................................................... 150
11.3 Staging of CKD in Children................................................................................................. 150
11.4 Pediatric Nutrition Assessment............................................................................................. 150
11.5 Nutrient Needs...................................................................................................................... 152
11.5.1 Energy Needs............................................................................................................. 152
11.5.2 Protein........................................................................................................................ 153
11.5.3 Fluid........................................................................................................................... 154
11.5.4 Sodium....................................................................................................................... 155
11.5.5 Potassium................................................................................................................... 156
11.5.6 Iron............................................................................................................................. 156
11.6 Bone Health.......................................................................................................................... 156
11.6.1 Calcium...................................................................................................................... 156
11.6.2 Phosphorus................................................................................................................. 157
11.6.3 Vitamin D.................................................................................................................. 157
11.6.4 Parathyroid Hormone................................................................................................ 158
11.7 Vitamin and Mineral Supplements....................................................................................... 159
11.8 Growth Hormone.................................................................................................................. 159
11.9 Nutrition Support.................................................................................................................. 160
11.9.1 Enteral Nutrition........................................................................................................ 160
11.9.2 Parenteral Nutrition................................................................................................... 160
11.10 Summary............................................................................................................................... 161
References....................................................................................................................................... 161
149
150 Nutrition Therapy for Chronic Kidney Disease
and interstitial nephritis. In contrast to adult causes of CKD, diabetic nephropathy and hypertension
are rare causes of pediatric CKD (NAPRTCS, 2010).
For example, a 6-year-old boy with a height of 120 cm and creatinine of 3 mg/dL would have a
GFR of 20. He would be classified as having stage 4 CKD and may be nearing the need for kidney
replacement therapy (Hogg et al., 2003).
TABLE 11.1
Stages of Chronic Kidney Disease
CKD Stage 1 2 3 4 5 or 5D
GFR (mL/ 90 6089 3059 1529 <15
min/1.73m2)
Stage description of With normal or Mild reduction of Moderate Severe reduction Kidney failure
kidney damage increased GFR GFR reduction of of GFR
GFR
Nutrition treatment Ensure adequate Modify diet as Modify diet as Continue to Modify diet
nutrition for necessary for necessary for further modify dependent on
growth, treat growth and growth; evaluate diet; prepare for dialysis treatment
comorbidites, estimate CKD and treat kidney
and monitor progression complications replacement
CVD risk therapy
Sources: Hogg, et al., Pediatrics, 111, 14161421, 2003; Heilbron, et al., Pediatr. Nephrol., 5, 511, 1991; NKF K/DOQI,
Am. J. Kidney Dis., 35, S1S140, 2000; NKF K/DOQI, Am. J. Kidney Dis., 53, S16S123, 2009.
Abbreviations: CKD, chronic heart disease; CVD, cardiovascular disease; GFR, glomerular filtration rate.
Nutrition for Children and Adolescents with Chronic Kidney Disease 151
weekly outpatient follow-up until a stable pattern of growth is established. Toddlers will likely
require monthly follow-up at least.
Recommended assessment components include dietary intake, height- or length-for-age percen-
tile or standard deviation score (SDS); height or length velocity-for-age percentile or SDS; estimated
dry weight and weight-for-age percentile or SDS; head circumference until age 3, and normal-
ized protein catabolic rate (nPCR). See Table 11.2 for recommended monitoring schedule (National
Kidney Foundations Kidney Disease Outcomes Quality Initiative, 2009).
Malnutrition is common in children with CKD. It is related to inadequate intake and is associ-
ated with anorexia, taste changes and a multitude of other gastrointestinal issues, including reflux,
especially in infants, and constipation, especially in those with polyuria.
The best markers of nutritional status are problematic with kidney disease. For example, fluid
overload makes it difficult to estimate lean body mass. Also, the child may appear to have adequate
weight for length or weight for height according to the growth grid but may be cachexic upon visual
exam. Arm anthropometry may be useful to document malnutrition in this child.
Protein malnutrition is common, related to inadequate intake associated with anorexia and the
taste changes reported by some with kidney disease. Here, the commonly used marker of albu-
min may not be useful because albumin may be normal in the setting of starvation and depressed
TABLE 11.2
Frequency of Nutritional Assessment for Children with CKD Stages 2 to 5 and 5 Dialysis
Minimum Interval in Months
Age 0 to <1 years Age 13 years Age >3 years
Measure CKD CKD CKD CKD CKD CKD CKD CKD CKD CKD
23 45 5D 23 45 5D 2 3 45 5D
Dietary intake 0.53 0.53 0.52 13 13 13 612 34 34 34
Height or 0.51.5 0.51.5 0.51 13 12 1 36 612 13 13
length-for age
percentile or SDS
Height or length 052 0.52 0.51 16 13 12 6 6 6 6
velocity-for-age
percentile or SDS
Estimated dry 0.51.5 0.51.5 0.251 13 12 0.51 36 36 13 13
weight and
weight-for-age
percentile or SDS
BMI-for-height- 0.51.5 0.51.5 0.51 13 12 1 36 36 13 13
age percentile or
SDS
Head 0.51.5 0.51.5 0.51 13 12 1 N/A N/A N/A N/A
circumference-
for-age percentile
or SDS
nPCR N/A N/A N/A N/A N/A N/A N/A N/A N/A 1a
Abbreviation:BMI, body mass index; CKD, chronic heart disease; N/A, not applicable; nPCR, normalized protein catabolic
rate; SDS, standard deviation score.
a Only applies to adolescents receiving HD.
Source: National Kidney Foundation. Am. J. Kidney Dis., 53, S1S124, 2009 (suppl 2). With permission.
152 Nutrition Therapy for Chronic Kidney Disease
in the setting of volume overload and inflammation. Hypoalbuminemia has been associated with
increased mortality in children as well as adults (Wong et al., 2002).
Pre-albumin is not typically used in the assessment of pediatric patients with CKD because lev-
els increase due to decreased clearance of the molecule with kidney disease.
Food records may supply valuable information for the nutrition assessment of a child. However,
the common problems of accurate completion and avoidance of recording foods not recommended
may yield false results.
Growth retardation is a common concern in children with CKD. Short stature has been associ-
ated with increases in morbidity and mortality (Wong et al., 2000). Adequate growth may continue
until significant wasting occurs (Behrman and Kliegman, 1996). Use of the SDS or z score is an
alternate method of expressing percentiles. For example, an SDS of 2 correlates with the second
percentile. An SDS of >2.5 has been associated with increased risk of death and increased hospi-
talization time (Wong et al., 2000).
Adequate intake of calories and protein is especially important for optimal growth. Growth and
development deficits acquired during infancy may never fully recover (Foster and Leonard, 2004).
TABLE 11.3
Estimated Daily Calorie Needs Children at Healthy Weights
Age (Years) Inactive Moderate Activity Active
23 either gender 10001200 10001400 10001400
48 12001400 14001600 16002000 Male
14001800 Female
913 14001600 Male 18002200 Male 20002600 Male
16002000 Female 16002000 Female 18002200 Female
1418 20002400 Male 24002800 Male 28003200 Male
1800 Female 2000 Female 2400 Female
Source: U.S. Department of Agriculture and U.S. Department of Health and Human Services.
Dietary Guidelines for Americans, 2010, U.S. Government Printing Office, December
2010, Washington, DC.
Nutrition for Children and Adolescents with Chronic Kidney Disease 153
FIGURE 11.1 Counseling session. (Courtesy of the National Institute of Diabetes and Digestive and Kidney
Diseases, National Institutes of Health.)
11.5.2 Protein
Protein intake is an important part of all childrens diets for general health reasons, such as preven-
tion of infection and illness, as well as optimal growth. The healthy child typically exceeds the
recommended daily allowance for protein. The young child takes in 35 times the estimated aver-
age requirement (Fulgoni, 2008). Although there are data suggesting that restricting protein intake
limits progression of kidney disease in adults, whether this is also true in pediatrics is controversial
and may be problematic (Chaturvedi and Jones, 2007). Limiting protein intake to recommended
daily needs may be helpful in reducing uremia and its side effects. However, it is important that the
child maintains adequate caloric intake for growth. Depending upon the family situation, limiting
protein may contribute to failure to thrive. Nutrition counseling is indicated to determine feasibility
of this therapy with each family (Figure 11.2).
The latest KDOQI pediatric guidelines decreased the recommended protein needs for pediatric
patients with CKD (Table 11.4). This resulted in lower protein recommendations for children on
dialysis than for adults on dialysis on a per-kilogram basis. For example, the recommendation for an
adolescent on hemodialysis is 0.95 g protein/kg, whereas the adult recommendation is 1.2 g protein/
kg (National Kidney Foundations Kidney Disease Outcomes Quality Initiative, 2009).
Individualization of protein goals remains important. Protein intake may be suboptimal due to
anorexia and preference for foods other than protein sources. Creative methods to increase protein
intake may be successful, including use of special recipes, modular supplements, protein-contain-
ing bars, and special shakes or smoothies.
Children on peritoneal dialysis have the highest estimated protein needs per kilogram. Dialysis-
related protein losses are variable. The risk for kwashiorkor exists if protein intake does not meet
needs, whereas energy needs can be partly met by the dextrose absorbed from dialysate.
Typical protein losses from peritoneal dialysis are reported as 0.28 g/kg in the first year of life
decreasing to less than 0.1 g/kg in adolescents (Quan and Baum, 1996). Additional protein requirements
range from 0.15 to 0.35 mg/kg, depending on age. Table 11.4 presents recommended protein intake.
High peritoneal transporters may need increased dietary protein. Studies on aminoacid and protein loss
have not been quantified on children. It is estimated that adding 0.1 g/kg/day of protein will meet needs
154 Nutrition Therapy for Chronic Kidney Disease
Hemodialyzer
(where filtering takes place)
FIGURE 11.2 Teenager on dialysis. (Courtesy of the National Institute of Diabetes and Digestive and Kidney
Diseases, National Institutes of Health.)
TABLE 11.4
Recommended Dietary Protein Intake in Children with CKD Stages 35 and 5 Dialysis
Recommended Recommended
Daily for CKD Stage for CKD Stages
Reference 3 (g/kg/day) 45 (g/kg/day) Recommended
Intake (DRI) (100%140% (100%120% for HD (g/kg/ Recommended for
Age (g/kg/day) DRI) DRI) day)a PD (g/kg/day)b
06 months 1.5 1.52.1 1.51.8 1.6 1.8
712 months 1.2 1.21.7 1.21.5 1.3 1.5
13 years 1.05 1.051.5 1.051.25 1.15 1.3
413 years 0.95 0.951.35 0.951.15 1.05 1.1
1418 years 0.85 0.851.2 0.851.05 0.95 1.0
Source: National Kidney Foundation, Am. J. Kidney Dis., 53, S1S124, 2009. With permission.
Abbreviations: CKD, chronic kidney disease; DRI, dietary reference intake.
a DRI + 0.1 g/kg/d to compensate for dialysis losses.
b DRI + 0.150.3 g/kg/d depending on patients age to compensate for peritoneal losses.
for children dialyzing 3 days per week. Increased protein needs would be expected with more frequent
dialysis (National Kidney Foundations Kidney Disease Outcomes Quality Initiative, 2009).
11.5.3 Fluid
Fluid goals are variable and dependent on the childs diagnosis, urine output, and other losses. The
infant with polyuria may require up to 240 mL fluid per kilogram, whereas the child with polyuria
may require several liters of fluid per day.
Nutrition for Children and Adolescents with Chronic Kidney Disease 155
FIGURE 11.3 Fluids. (Courtesy of the National Institute of Diabetes and Digestive and Kidney Diseases,
National Institutes of Health.)
Urine output commonly decreases on dialysis. Limiting fluid input to urine output plus insensible
losses is generally recommended. This may require use of very concentrated formulations to meet
the needs of those primarily fed by liquid formulas. For example, a typical infant formula contains
20 calories per ounce. To meet caloric needs of a child with CKD and a fluid restriction, formula
may need to be gradually concentrated to greater than 40 calories per ounce.
Children on hemodialysis (HD) often require a very restricted fluid intake for optimal dialy-
sis runs. It may be necessary to dialyze an infant daily to meet caloric needs until the transition
to a concentrated formula is tolerated. It is important to provide adequate nutrition for growth.
Increasing frequency of dialysis to allow adequate nutritional intake may not be popular with fam-
ily or staff but may be necessary for growth. Transitioning to peritoneal dialysis may result in a
liberalization of fluid restriction (Figure 11.3).
11.5.4 Sodium
Infants or children with kidney disease may need increased sodium intake for optimal growth
or may need to limit sodium intake owing to problems with fluid retention and/or hypertension.
Limiting sodium intake is a major challenge for families used to eating and cooking with processed
foods and eating out. Involving the entire family in the new lower sodium diet is recommended.
The American Heart Association recommends that all Americans decrease their sodium intake to
less than 1500 mg/day (Lloyd-Jones et al., 2010). The entire family may benefit from the sodium
reduction, and the child will likely better meet recommendations if the whole family transitions to
a low-sodium diet. Given that the typical American consumes 3400 mg sodium per day, reducing
sodium intake to the recommended levels may be a drastic change, and adaptation will take time.
Children with nephrotic syndrome are placed on a low-sodium diet at diagnosis, and it is recom-
mended that it be continued during remissions due to the difficulty of readjusting to a low-sodium
diet during disease flares.
Conversely, infants and children with polyuria may benefit from sodium supplementation for opti-
mal growth. A study of infants and toddlers found that sodium supplementation in the form of chlo-
ride and/or bicarbonate at doses of 24 mEq/100 ml fluid intake and a fluid intake of 180240 ml/kg
resulted in improvements in linear growth without the aid of growth hormone (Parekh et al., 2001).
156 Nutrition Therapy for Chronic Kidney Disease
Medications such as sodium phosphate, sodium bicarbonate, sodium chloride, and sodium polysty-
rene sulfonate administered to treat other renal-related abnormalities may add to the sodium intake.
11.5.5 Potassium
Potassium typically needs to be limited as disease progresses to Stage 5. Infants may be placed
on breast milk treated with sodium polystyrene sulfonate or on a low-potassium infant formula.
Standard progression for infant feeding is followed utilizing low-potassium fruits and vegetables.
Rather than advance to regular milk at 1 year of age as per usual pediatric guidelines, a low-
potassium infant formula is often continued to help control both potassium and phosphorus intake.
Potassium control may be easier than sodium control for many children. Learning to choose low-
potassium beverages and to limit high-potassium fruits and vegetables becomes second nature for
most children and they seem to easily transition back to the limitation if needed temporarily during
the post-transplant period and if the transplanted kidney fails.
11.5.6 Iron
Iron supplementation becomes an important part of the life of the infant or child with kidney dis-
ease. Maintaining iron stores is important to help maintain energy for the normal activities of
childhood and to prevent anemia-related learning problems. The healthy infant typically requires
iron supplementation during the first year of life to ensure normal levels and prevent failure to
thrive and learning issues. In addition, the infant or child with kidney disease frequently receives
erythropoietic-stimulating agents to help achieve optimal iron status.
Parents often note the effects of iron supplementation such as black stools and constipation. Stool
softeners may be included in the daily regimen in order to prevent problems such as the anorexia,
abdominal pain, and vomiting experienced with severe constipation.
11.6.1 Calcium
Hypercalcemia and hypocalcemia are seen in infants and children with kidney disease. It is recom-
mended that the dietary reference intake (DRI) for calcium be the goal, adjusted as needed based
on clinical status. The 2011 DRIs for calcium include the selected expansion of the upper levels of
intake, especially during the teenage years. At this time, there is no evidence that these parameters
will be acceptable for children with CKD. Table 11.5 shows the new data.
Hypocalcemia is commonly seen in the child with newly diagnosed end-stage disease. Calcium
supplementation between meals can help to normalize labs and if taken with meals provides phos-
phorus binding. Calcium in liquid form is available and is especially useful with infant and toddlers
and in older children with swallowing issues.
Calcium intake varies with age, but one should ensure that the the upper limits of calcium
intake are not exceeded once the hypocalcemic period resolves. The risk of mineral deposits
throughout the body increases with an elevated calcium and phosphorus product (serum calcium
times serum phosphorus). The calcium phosphorus product should be less than 65 for young chil-
dren and less than 55 for those older than 12 years (National Kidney Foundations Kidney Disease
Outcomes Quality Initiative, 2005).
Nutrition for Children and Adolescents with Chronic Kidney Disease 157
TABLE 11.5
Recommended Calcium Intake for Children with CKD Stages 25 and 5 Dialysis
Upper Limit for CKD Stages
Upper Limit (for New 2011 Upper Limit 25, 5D (Dietary +
Age DRI Healthy Children) Changesa Phosphate Binders)
06 months 210 ND 1000 420
712 months 270 ND 1500 540
13 years 500 2500 No change 1000
48 years 800 2500 No change 1600
918 years 1300 2500 3000 2500
Source: Some data in the table reproduced from National Kidney Foundation, Am. J. Kidney Dis., 53, S1S124, 2009. With
permission.
Abbreviations: CKD, chronic kidney disease, DRI, dietary reference intake; ND, not determined.
a Column insert from the Institute of Medicine, National Academies, DRIs for Calcium, 2011.
Hypercalcemia may be associated with calcium supplements and vitamin D therapies of the
active form, and less frequently, the inactive form. Also, hypercalcemia may be seen in vitamin A
toxicities associated with kidney disease. Treatment involves discontinuing supplements or adjust-
ing formula and diet to decrease vitamin A and calcium intake. Avoiding use of topical agents
containing vitamins A and D is also recommended (National Kidney Foundations Kidney Disease
Outcomes Quality Initiative, 2009).
11.6.2 Phosphorus
Finding the balance between adequate but not excessive phosphorus intake is a challenge in man-
aging most infants and children with kidney disease and is exacerbated as the older child and
adolescent become more independent. As with calcium, maintaining normal phosphorus levels is
recommended to promote optimal bone health and prevent mineral deposits throughout the body.
The infant may need phosphorus supplementation. Intravenous products, such as sodium phos-
phate for injection, may be used enterally if the infant is too young to tolerate other methods of
increasing phosphorus intake.
Limiting dietary phosphorus and including phosphorus-binding agents in the diet are important
components of the nutrition plan for children with kidney disease. The official guideline is to limit
phosphorus intake to varying percentages of the DRI. Helping families understand that limiting
dairy products and finding alternatives is a first step in phosphorus control education. Low-mineral
infant formulas and specially designed adult renal formulas may help control phosphorus intake
while maintaining adequate nutritional intake.
Phosphorus binders taken with meals and snacks along with a low-phosphorus diet can control
phosphorus levels. Hyperphosphatemia may be seen in a child who is not eating, so caution is
advised before assuming nonadherence. If calcium-based binders are needed at levels that exceed
upper limits of calcium, the use of noncalciumcontaining binders is recommended. Variations of
the sevelamer product are frequently used. The powdered form can be used by those infants and
children who are unable to take the pill form.
11.6.3 Vitamin D
The promotion of optimal vitamin D levels for the prevention of various diseases has caught the
attention of the general press. Children with CKD, like healthy children, may require supplemen-
tation to achieve normal levels. Guidelines for monitoring of 25-hydroxy vitamin D levels and
158 Nutrition Therapy for Chronic Kidney Disease
TABLE 11.6
Recommended Supplementation for Vitamin D Deficiency/Insufficiency in Children with
CKD
Serum 25 (OH) Ergocalciferol (Vitamin D2) or
D (ng/mL) Definition Cholecalciferol (Vitamin D3) Dosing Duration (months)
<5 Severe vitamin D deficiency 8000 IU/day orally or enterally 4 weeks 3
or (50,000 IU twice per month for 2
months) 2 months
515 Mild vitamin D deficiency 4000 IU/day orally or enterally 12 weeks 3
or (50,000 IU every other week, for 12
weeks)
1630 Vitamin D insufficiency 2000 IU/day or (50,000 IU every 4 weeks) 3
Source: National Kidney Foundation, Am. J. Kidney Dis., 53, S1S124, 2009. With permission.
Abbreviation: CKD, chronic kidney disease.
FIGURE 11.4 Calcitriol. (Courtesy of the National Institute of Diabetes and Digestive and Kidney Diseases,
National Institutes of Health.)
supplementation are provided by the pediatric KDOQI guidelines (Table 11.6). Provision of both
the inactive and active forms of vitamin D may be needed by children with kidney disease. The
inactive form of vitamin D can be given on a weekly or monthly basis if the daily pill burden from
other medications is limiting adherence to the medication regimen (National Kidney Foundations
Kidney Disease Outcomes Quality Initiative, 2009).
Hypercalcemia while the child is on active vitamin D may be treated by discontinuing or
decreasing active vitamin D or by initiating a trial of an alternate vitamin D analog that may cause
less hypercalcemia. A review of the childs diet and supplements for excess calcium and vitamin A
intake is also indicated (Figure 11.4).
TABLE 11.7
Recommended Frequency of Measurement for Bone
Disease Markers
Calcium, Phosphorus, PTH and Alkaline
Stage GFR Total CO2 Phosphatase
3 3059 Semi-annually Semi-annually
4 1529 Quarterly Quarterly
5 <15 Monthly Quarterly
utilize their natural growth hormone. Children must be receiving adequate nutritional intake before
growth hormone is initiated. Correction of acidosis, hyperphosphatemia, and hyperparathyroidism
should have occurred prior to growth hormone initiation. Administration typically begins after the
first year of life and is most effective in toddlers started on it before the age of two. Growth hormone
is most effective in the first year of use. Growth hormone administration usually involves a daily
injection. One study reported height increases of 10.7 3.1 cm/year versus 6.5 2.6 cm/year for
the first year and 7.8 2.1 cm/year versus 5.5 1.9 for the second year of growth hormone (Mahan
et al., 2006).
Growth velocity should be monitored, with the expectation that height velocity will reach above
average levels so that catch-up height may be achieved. Calculations for mid-parental height can
provide an indication of expected genetic height potential for the child. Paternal height (cm) plus
maternal height (cm) plus 13 cm/2 is predictive for boys. For girls, add together paternal and mater-
nal heights (cm) and then subtract 13 cm/2 (Abitbol et al., 1996).
11.10 SUMMARY
The child with CKD faces many challenges as does the team providing care. As the stage of CKD
progresses, the child will require frequent monitoring in order to optimize nutritional status and
growth. Diets for children with CKD are as individualized and as liberal as possible to promote
adequate intake. Families will require frequent, ongoing education and support as their child grows
and they transition through the stages of CKD with their child. A multidisciplinary team consist-
ing of a pediatric dietitian along with other pediatric specialists including nurses, social workers,
therapists, and nephrologists will help the child achieve optimal growth and nutritional status.
REFERENCES
Abitbol, C., Chan, J., Trachtman, H., et al. 1996. Growth in children with moderate renal insufficiency:
Measurement, evaluation, and treatment. J Pediatr 129(2):S3S8.
Behrman, R. and Kliegman, R. 1996. Nelson Textbook of Pediatrics. Edited by R.E.K. Behrman, Robert;
Nelson, Waldo E. 15th edition. Philadelphia, PA: WB Saunders.
Chaturvedi, S. and Jones, C. 2007. Protein restriction for children with chronic renal failure. Cochrane
Database Syst Rev (4):CD006863.
Foster, B. and Leonard, M. 2004. Measuring nutritional status in children with chronic kidney disease. Am J
Clin Nutr 80(4):801814.
Fulgoni, V. 2008. Current protein intake in America: Analysis of the National Health and Nutrition Examination
Survey, 20032004. Am J Clin Nutr 87(5):1554S1557S.
Heilbron, D., Holliday, M., Al-Dahwi, A., et al. 1991. Expressing glomerular filtration rate in children. Pediatr
Nephrol 5(10):511.
Hogg, R., Furth, S., Lemley, K., et al. 2003. National Kidney Foundations Kidney Disease Outcomes Quality
Initiative clinical practice guidelines for chronic kidney disease in children and adolescents: Evaluation,
classification, and stratification. Pediatrics 111 (6 Pt 1):14161421.
Intakes, Subcommittees on Upper Reference Levels of Nutrients and Interpretation and Uses of Dietary
Reference Intakes; Standing Committee on the Scientific Evaluation of Dietary Reference. 2002. Dietary
Reference Intakes for Energy, Carbohydrate, Fiber, Fat, Fatty Acids, Cholesterol, Protein, and Amino
Acids (Macronutrients). Washington, D.C.: National Academies.
Kher, K., Schnaper, H., and Makker, S. 2007. Clinical Pediatric Nephrology. Edited by K. K. Kher, H. W.
Schnaper and S. P. Makker. 2nd ed. London: Informa Healthcare.
Ledermann, S., Shaw, V., and Trompeter, R. 1999. Long-term enteral nutrition in infants and young children
with chronic renal failure. Pediatr Nephrol 13(9):870875.
Lloyd-Jones, D., Hong, Y., Labarthe, D., et al. 2010. Defining and setting national goals for cardiovascular
health promotion and disease reduction: The American Heart Associations strategic Impact Goal through
2020 and beyond. Circulation 121(4):586613.
Mahan, J., Warady, B., and Committee Consensus. 2006. Assessment and treatment of short stature in pediatric
patients with chronic kidney disease: A consensus statement. Pediatr Nephrol 21(7):917930.
NAPRTCS (North American Pediatric Renal Trials and Collaborative Studies). 2010. Annual Transplant Report.
National Kidney Foundations Kidney Disease Outcomes Quality Initiative. 2005. Clinical practice guide-
lines for bone metabolism and disease in children with chronic kidney disease. Am J Kidney Dis 46 (4,
Suppl1):S1S122.
162 Nutrition Therapy for Chronic Kidney Disease
National Kidney Foundations Kidney Disease Outcomes Quality Initiative. 2009. KDOQI clinical practice
guideline for nutrition in childrens with CKD: 2008 Update. Am J Kidney Dis 53 (3, Suppl 2):S16S123.
Nutrition, The American Society for Parenteral and Enteral. 2002. Guidelines for the use of parenteral and
enteral nutrition in adult and pediatric patients. J Parent Ent Nutrit 26(1):1SA138SA.
Orellana, P., Juarez-Congelosi, M., and Goldstein, S. 2005. Intradialytic parenteral nutrition treatment and
biochemical marker assessment for malnutrition in adolescent maintenance hemodialysis patients. J Ren
Nutr 15(3):312317.
Parekh, R., Flynn, J., Smoyer, W., et al. 2001. Improved growth in young children with severe chronic renal
insufficiency who use specified nutritional therapy. J Am Soc Nephrol 12(11):24182426.
Quan, A. and Baum, M. 1996. Protein losses in children on continuous cycler peritoneal dialysis. Pediatr
Nephrol 10(6):728731.
Schwartz, G., Munoz, A., Schneider, M., et al. 2009. New equations to estimate GFR in children with CKD.
JAm Soc Nephrol 20 (3):629637.
U.S. Department of Agriculture and U.S. Department of Health and Human Services. December 2010. Dietary
Guidelines for Americans, 2010. 7thEd., Washington, DC: U.S. Government Printing Office.
U.S. Renal Data System. 2010. USRDS 2010 Annual Data Report: Atlas of Chronic Kidney Disease and End-
Stage Renal Disease in the United States. Bethesda, MD: National Institutes of Health, National Institute
of Diabetes and Digestive and Kidney Diseases.
Wong, C., Gipson, D., Gillen, D., et al. 2000. Anthropometric measures and risk of death in children with end-
stage renal disease. Am J Kidney Dis 36 (4):811819.
Wong, C., Hingorani, S., Gillen, D., et al. 2002. Hypoalbuminemia and risk of death in pediatric patients with
end-stage renal disease. Kidney Int 61 (2):630637.
12 Pregnancy and Kidney Disease
Jeannine C. Lawrence
University of Alabama
CONTENTS
12.1 Background............................................................................................................................ 163
12.2 Physiology in Pregnancy and Renal Disease......................................................................... 164
12.3 Assessment/Evaluation of Pregnant Patient with CKD......................................................... 165
12.3.1 Clinical Data.............................................................................................................. 165
12.3.2 Medical History/Medications.................................................................................... 165
12.3.3 Dietary Intake............................................................................................................ 165
12.3.4 Physical Activity........................................................................................................ 165
12.4 Nutrition Prescription............................................................................................................ 165
12.4.1 Weight Gain............................................................................................................... 165
12.4.2 Macronutrients........................................................................................................... 166
12.4.3 Micronutrients........................................................................................................... 167
12.5 Medications with Nutritional Implications............................................................................ 167
12.5.1 Hypertension.............................................................................................................. 167
12.5.2 Anemia...................................................................................................................... 167
12.5.3 Electrolyte and AcidBase Disturbances.................................................................. 167
12.5.4 Transplantation.......................................................................................................... 167
12.6 Managing Comorbidities....................................................................................................... 169
12.7 Postpregnancy and Breastfeeding.......................................................................................... 169
References....................................................................................................................................... 169
12.1 BACKGROUND
Pregnancy in women with kidney disease or renal failure is an infrequent occurrence. Generally,
more severe kidney dysfunction along with a higher number of associated comorbidities, means it
is more likely that a womans fertility will be impaired and that an ensuing pregnancy will be more
complicated (Piccoli et al., 2010a; Vidaeff et al., 2008). It is estimated that the pregnancy rate of
women of childbearing age with renal disease ranges from 0.03% to 7% (Fink et al., 1998; Holley
and Reddy, 2003), which is well below the estimated pregnancy rate of 10.3% in the general U.S.
population (CDC, 2009). Causes for the reduction in pregnancy rates in women with renal disease
are not completely understood; however, it is known that there is a marked reduction in presence of
menses and/or ovulation in women undergoing dialysis (Holley et al., 1997; Piccoli et al., 2010b).
Once pregnancy has begun, it is considered to be high risk and requires complex and intensive man-
agement by the health-care team (Figure 12.1).
In case of pregnancy in women with mild kidney disease, the pregnancy itself does not result in
a chronic decrease in kidney function but may result in alternative damaging effects, such as devel-
opment of proteinuria, preeclampsia, and/or initiation or exacerbation of preexisting hypertension
(Fischer, 2007). However, as the severity of the maternal kidney disease increases to moderate or
severe, a concomitant decline in kidney function during pregnancy can be seen (Fischer, 2007).
Accordingly, the effects of maternal kidney disease on fetal outcomes vary based on the severity
163
164 Nutrition Therapy for Chronic Kidney Disease
FIGURE 12.1 Prenatal care. (Courtesy of National Institute of Diabetes and Digestive and Kidney Diseases,
National Institutes of Health.)
of the disease. In cases of mild maternal kidney disease, successful pregnancy outcomes have been
described in 68%98% of observed pregnancies, with no obstetrical or fetal complications reported in
approximately 65% of these pregnancies (Bar et al., 2000; Chapman et al., 1994; Holley et al., 1996).
These data contrast markedly with fetal outcomes in women with severe kidney disease. In this group,
pregnancy is extremely rare and, when it does occur, typically it results in preterm delivery, intrauter-
ine growth retardation, or fetal death (Fischer, 2007). Dialysis, especially daily dialysis treatments,
can be an important therapeutic tool in improving maternal and fetal outcomes in maternal kidney
disease (Piccoli et al., 2010b). The goal of nutritional intervention in maternal kidney disease is to find
the appropriate balance between minimizing the intake of nutrients detrimental to kidney function
and reducing toxemia while still providing appropriate nutrition for the developing fetus.
Conversely, in postrenal transplant patients, pregnancy is relatively common, and medical man-
agement is more focused on management of risks associated with immunosuppressive medications.
The goal of nutritional intervention in postrenal transplant patients during pregnancy is typically
oriented toward maintaining an appropriate rate of weight gain and monitoring the development of
potential comorbidities including, most notably, type 2 diabetes mellitus.
who undergoes a peritoneal dialysis (PD) regimen with daily dialysate exchanges may become
uncomfortable using her prepregnancy exchange volumes in later pregnancy. To accommodate the
decreased availability of abdominal space, the clinician may prescribe a reduced exchange volume
with a higher number of exchanges performed daily (Hou, 1999). These alterations in dialysis pre-
scription will necessarily affect the nutrition prescription.
FIGURE 12.2 Dietary counseling. (Courtesy of National Institute of Diabetes and Digestive and Kidney
Diseases, National Institutes of Health.)
TABLE 12.1
Recommendations for Weight Gain during Pregnancy
Total Weight Gain Range
Prepregnancy Body Mass Index (kg/m2) Single Pregnancy (kg/lbs) Twin Pregnancy (kg/lbs)
<18.5 (Underweight) 12.518/2840 Insufficient data available to set guidelines
18.524.9 (Normal weight) 11.516/2535 1725/3754
25.029.9 (Overweight) 711.5/1525 1423/3150
30.0 (Obese) 59/1120 1119/2542
mothers pregravid body mass index (BMI; Rasmussen et al., 2009). In patients receiving dialysis,
dry weight should be used for BMI calculation (Table 12.1).
12.4.2 Macronutrients
Once the total energy and protein needs have been established, the remaining calories can be dis-
tributed between fat and carbohydrate sources. As coronary heart disease is the leading cause of
death in patients undergoing HD, PD, or kidney transplantation (Kasiske et al., 2004), recommen-
dations for dietary fat intake are modified based on the absence or presence of hyperlipidemia. In
the absence of hyperlipidemia, minimize cardiovascular disease (CVD) risk by implementing the
American Heart Association guidelines, including limiting saturated fat (<7% of energy), trans
fats (<1%), and cholesterol intake (<300 mg/day). In the presence of hyperlipidemia, implement the
Therapeutic Lifestyle Changes dietary goals for fat intake, including a total fat intake of 25%35%
of calories, with a saturated fat intake of <7% of calories and the remaining bulk of fat calories (up
to 20%) distributed primarily toward monounsaturated fats and secondarily toward polyunsaturated
fats and cholesterol of <200 mg/day (NCEP Panel, 2002). Remaining calorie requirements are to be
met with carbohydrate sources.
Pregnancy and Kidney Disease 167
12.4.3 Micronutrients
Patients in stages 13 of chronic kidney disease (CKD) or postrenal transplantation are advised
to take a standard prenatal vitamin daily. However, patients in later stages of CKD or in ESRD
are typically prescribed a standard, water-soluble renal vitamin dosage that is double the typical,
nonpregnancy dosage. In cases of dialysis, the recommendations for folic acid intake are increased
due to increased losses during dialysis. In these patients, 1.8 mg of folic acid is recommended daily
(Hou, 1999; Stover, 2007). In addition, micronutrients that may require supplementation if they are
not provided in adequate amounts in the standard multivitamin dosage prescribed during pregnancy
include vitamin D, calcium, iron, and zinc (15 mg/dL; Stover, 2007) (Table 12.2).
12.5.2 Anemia
Anemia is a common complication during pregnancy and is even more frequently observed in
pregnant patients receiving HD. Oral iron supplements may be used to treat milder cases of anemia.
However, intravenous (IV) iron, in the forms of iron sucrose or iron gluconate, may be used if oral
supplements prove ineffective (Vidal et al., 1998). It should be noted that the use of IV iron prepara-
tions may result in increased absorption by the fetus with subsequent acute iron toxicity (Hou and
Firanek, 1998). Therefore, this route of administration is to be used conservatively and monitored
carefully.
12.5.4 Transplantation
Maternal immune suppression is essential during pregnancy; therefore, the effects of certain
immunosuppressive agents at this lifecycle stage are well studied. The primary agents used for
immune suppression in this population are prednisone, azathioprine, cyclosporine, and tacroli-
mus (Vidaeff et al., 2008). Although each has demonstrated potential risks to fetal development,
these risks are outweighed by the potential costs of insufficient immune suppression to both the
mother and the fetus. Nutrition considerations during pregnancy, which are related to the use
of these drugs, include osteopenia (prednisone); exacerbation of diabetes or increased risk of
development of gestational diabetes (prednisone, cyclosporine, and tacrolimus); hypertension
(prednisone and cyclosporine); and elevated creatinine levels (cyclosporine) (American College
of Rheumatology Ad Hoc Committee on Clinical Guidelines, 2006; Kitridou, 1997; Kainz etal.,
2000).
168 Nutrition Therapy for Chronic Kidney Disease
TABLE 12.2
Nutritional Guideline for Pregnant Patients with CKD and for Patients on Dialysis or
Postrenal Transplant
Energy
CKD/HD/PD First trimester: BEE activity factor (1.21.4) or 35 kcal/kg prepregnancy IBWa; second and
third trimesters: add 300 kcal/dLb
Posttransplantation First trimester: BEE activity factor (1.21.4) or 2535 kcal/kg prepregnancy IBW; second
and third trimesters: add 300 kcal/dL
Protein
CKD Stages 13: 0.8 g/kg + 10 g/day
Stages 45 without dialysis: 0.6 g/kg + 10 g/dayc
HD 1.11.4 g/kg prepregnancy IBW + 10 g/day
PD 1.21.5 g/kg prepregnancy IBW + 10 g/day
Posttransplantation 1.01.2 g/kg prepregnancy IBW + 10 g/day
Fluid
CKD Unrestricted unless fluid retention is present
HD 10002000 mL/interdialytic interval, not to exceed 2 kg interdialytic fluid weight gain
PD Sufficient to maintain fluid balance. Monitor fluid retention status
Posttransplantation Unrestricted unless fluid retention is present
Calcium
CKD 1000 mg/day
HD/PD Individualizedevaluate serum Ca++, phosphorus, and PTH values; ~10001200 m
g/day.
Evaluate calcium concentration of dialysate and phosphate binder dosage
Posttransplantation 12001500 mg/day
Phosphorus
CKD/HD/PD Individualized per serum values; ~1200 mg/day
Posttransplantation 1200 mg/day
Potassium
CKD Unrestricted unless hyperkalemic, then 24 g/day
HD Individualized per serum values; ~40 mg/kg prepregnancy IBW
PD Individualized per serum values, may not require restriction
Posttransplantation Unrestricted unless hyperkalemic, then 24 g/day
Sodium
CKD Individualizedevaluate serum values, blood pressure, and fluid retention status; ~24 g/day
HD Individualizedevaluate serum values, blood pressure, and fluid retention status; ~23 g/day
PD Individualizedevaluate serum values, blood pressure, and fluid retention status; ~24 g/day
Posttransplantation Individualized; ~24 g/day
Source: Hou, S., Am. J. Kidney Dis., 33, 235252, 1999; Stover, J., Adv. Chronic Kidney Dis., 14, 212214, 2007; and
Wiggins, K. and Harvey, K., J. Ren. Nutr., 12, 190196, 2002.
Abbreviations: CKD, chronic kidney disease; HD, hemodialysis; PD, peritoneal dialysis; PTH, parathyroid hormone.
a IBW = Ideal Body Weight
b When calculating energy prescription for women receiving PD, be certain to factor in glucose calories received from the
dialysate solution.
c Recognize that while this protein goal is recommended to minimize the deterioration of kidney function, it may not be
achievable given the increased total energy needs required during pregnancy.
Pregnancy and Kidney Disease 169
REFERENCES
ACOG Committee. 2002. Opinion no. 267: Exercise during pregnancy and the postpartum period. Obstet
Gynecol. 99:171173.
American Academy of Pediatrics Committee on Drugs. 1994. The transfer of drugs and other chemicals into
human milk. Pediatrics. 93:137150.
American College of Rheumatology Ad Hoc Committee on Clinical Guidelines. 1996. Guidelines for monitor-
ing drug therapy in rheumatoid arthritis. Arthritis Rheum. 39:723731.
Artal, R. and OToole, M. 2003. Guidelines of the American College of obstetricians and gynecologists for
exercise during pregnancy and the postpartum period. Br J Sports Med. 37: 612.
Bar, J., Ben-Rafael, Z., Padoa, A., et al. 2000. Prediction of pregnancy outcome in subgroups of women with
renal disease. Clin Nephrol. 53(6):437444.
Brookhyser, J. 1989. The use of parenteral nutrition supplementation in pregnancy complicated by end-stage
renal disease. J Am Diet Assoc. 89(1):9394.
Centers for Disease Control (CDC). October 14, 2009. Estimated pregnancy rates for the United States, 1990
2005: An update. Natl Vital Stat Rep. 58(4):2.
Chapman, A., Johnson, A. and Gabow, P. 1994. Pregnancy outcome and its relationship to progression of renal
failure in autosomal dominant polycystic kidney disease. J Am Soc Nephrol. 5(5):1178185.
Erick, M. 2008. Nutrition during pregnancy and lactation. In Mahan, L.K., and Escott-Stump, S. eds. Krauses
Food and Nutrition Therapy. St. Louis, MO: Saunders Elsevier, 187.
Fink, J., Schwartz, S., Benedetti, T., et al. 1998. Increased risk of adverse maternal and infant outcomes among
women with renal disease. Paediatr Perinat Epidemiol. 12(3):277287.
170 Nutrition Therapy for Chronic Kidney Disease
Fischer, M. 2007. Chronic kidney disease and pregnancy: Maternal and fetal outcomes. Adv Chronic Kidney
Dis. 14(2):132145.
Holley, J., Bernardini, J., Quadri, K., et al. 1996. Pregnancy outcomes in a prospective matched control study
of pregnancy and renal disease. Clin Nephrol. 45(2):7782.
Holley, J. and Reddy, S. 2003. Pregnancy in dialysis patients: A review of outcomes, complications, and man-
agement. Semin Dial. 16(5):384388.
Holley, J., Schmidt, R., Bender, F., et al. 1997. Gynecologic and reproductive issues in women on dialysis. Am
J Kidney Dis. 29(5):685690.
Hou, S. 1999. Pregnancy in chronic renal insufficiency and end-stage renal disease. Am J Kidney Dis.
33(2):235252.
Hou, S. and Firanek, C. 1998. Management of the pregnant dialysis patient. Adv Ren Replace Ther. 5(1):2430.
Hyten, F. 1988. Nutrition and metabolism. In: Hyten, F., ed., Clinical Physiology in Obstetrics. Oxford,
England: Blackwell Scientific Publications, 177.
Josephson, M. and McKay, D. 2007. Considerations in the medical management of pregnancy in transplant
recipients. Adv Chronic Kidney Dis. 14(2):156167.
Kainz, A., Harabacz, I., Cowlrick, I., et al. 2000. Review of the course and outcome of 100 pregnancies in 84
women treated with tacrolimus. Transplantation. 27; 70(12):17181721.
Kasiske, B., Cosio, F., Beto, J., et al. 2004. National Kidney Foundation. Clinical practice guidelines for man-
aging dyslipidemias in kidney transplant patients: A report from the managing dyslipidemias in Chronic
Kidney Disease Work Group of the National Kidney Foundation Kidney Disease Outcomes Quality
Initiative. Am J Transplant. 4(S7):1353.
Kitridou, R. 1997. The mother in systemic lupus erythematosus. In Wallace, D.J. and Hahn, B.H. Dubois
Lupus Erythematosus 5th ed., Baltimore, MD: Williams & Wilkins, 9671002.
Korzets, A., Azoulay, O., Ori, Y., et al. 2008. The use of intradialytic parenteral nutrition in acutely ill haemo-
dialysed patients. J Ren Care. 34(1):148.
Lindheimer, M. and Katz, A. 1992. Renal physiology and disease in pregnancy. In Seldin, D.W. and Giebisch,
G. eds. The Kidney: Physiology and Pathophysiology, 2nd ed., New York: Raven Press, 33713405.
Lindheimer, M. and Katz, A. 2001. The normal and diseased kidney in pregnancy. In Schrier, R.W., ed. Diseases
of the Kidney and Urinary Tract, 7th ed., Philadelphia, PA: Lippincott Williams and Wilkins, 21292165.
Maynard, S. and Thadhani, R. 2009. Pregnancy and the kidney. J Am Soc Nephrol. 20(1):1422.
National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment
of High Blood Cholesterol in Adults (Adult Treatment Panel III). 2002. Third Report of the National
Cholesterol Education Program (NCEP) expert panel on detection, evaluation, and treatment of high
blood cholesterol in adults (Adult Treatment Panel III) final report. Circulation. 106(25):31433421.
Piccoli, G., Attini, R., Vasario, E. et al. 2010a. Pregnancy and chronic kidney disease: A challenge in all CKD
stages. Clin J Am Soc Nephrol. 5(5):844855.
Piccoli, G., Conijn, A., Consiglio, V. et al. 2010b. Pregnancy in dialysis patients: is the evidence strong enough
to lead us to change our counseling policy? Clin J Am Soc Nephrol. 5(1):6271.
Rasmussen, K., Yaktine, A., eds. Committee to Reexamine IOM Pregnancy Weight Guidelines; Institute of
Medicine; National Research Council. 2009. Weight gain during pregnancy: Reexamining the guidelines.
Online: http://www.nap.edu/catalog/12584.html (accessed January 1, 2011).
Stover, J. 2007. Nutritional management of pregnancy in chronic kidney disease. Adv Chronic Kidney Dis.
14(2):212214.
Stover, J. 2008. Pregnancy. In: Byham-Gray, L., Burrowes, J. and Chertow, G. eds. Nutrition and Health:
Nutrition in Kidney Disease. Totowa, NJ: Humana Press, 419329.
Sturgiss, S., Dunlop, W. and Davison, J. 1994. Renal haemodynamics and tubular function in human pregnancy.
Baillieres Clin Obstet Gynaecol. 8(2):209234.
Tuot, D., Gibson, S., Caughey, A., et al. 2010. Intradialytic hyperalimentation as adjuvant support in pregnant
hemodialysis patients: Case report and review of the literature. Int Urol Nephrol. 42(1):233237.
Vidal, M., Ursu, M., Martinez, A., et al. 1998. Nutritional control of pregnant women on chronic hemodialysis.
J Ren Nutr. 8(3):150156.
Vidaeff, A., Yeomans, E. and Ramin, S. 2008. Pregnancy in women with renal disease. Part I: General prin-
ciples. Am J Perinatol. 25(7):385397.
Wiggins, K. and Harvey, K. 2002. A review of guidelines for nutrition care of renal patients. J Ren Nutr.
12(3):190196.
Williams, D. and Davison, J. 2008. Chronic kidney disease in pregnancy. BMJ. 26; 336(7637):211215.
13 Obesity and Physical Activity
Tanis Vye Mihalynuk
Acadia University
CONTENTS
13.1 Introduction........................................................................................................................... 171
13.2 Energy Balance...................................................................................................................... 172
13.3 Physical Activity.................................................................................................................... 172
13.4 PA and QoL........................................................................................................................... 177
13.5 Obesity and Weight Management.......................................................................................... 177
13.6 Obesity Paradox..................................................................................................................... 179
13.7 Conclusions............................................................................................................................ 179
References....................................................................................................................................... 180
13.1 INTRODUCTION
Obesity increases the risk of several chronic diseases, such as type 2 diabetes, hypertension, car-
diovascular disease (CVD), inflammatory disorders, common cancers, depression, and chronic
kidney disease (CKD). Although the global incidence of CKD is on the rise, it is termed a silent
epidemic (Stenvinkel, 2010). Pandemic trends in overweight and obesity may be largely respon-
sible for eclipsing this public health problem. Although there are various causes of CKD, there is
a growing evidence that obesity is a risk factorindependent of conditions such as diabetes and
CVD (Eknoyan, 2006; Ting et al., 2009). A Swedish case-control study of over 900 cases and
matched controls with chronic renal failure (CRF) showed a threefold increase in CRF among
cases who were overweight at the age of 20 (Ejerblad et al., 2006). Moreover, a recent systematic
review and meta-analysis estimated that in the United States, about one-fourth and one-third of
cases with kidney disease among men and women, respectively, could be attributed to overweight
and obesity (Wang et al., 2008).
It has been established that kidney damage leads to discharge of protein into the urine
(albuminuria and proteinuria) and subsequent muscle wasting and anemia as well as higher
blood pressure. Several mechanisms by which excess body weight further alters renal physiology,
including insulin resistance, increase in oxidative, endoplasmic reticulum, and proinflammatory
stresses, impairment of fibrinolysis, dysregulation of the reninangiotensinaldosterone system,
and compensatory hyperinsulinemia (Lastra et al., 2006), have been proposed. More recent ones
include lipid accumulation in the kidney (Corpeleijn et al., 2009) and secretion of adverse signal-
ing molecules, including adipokines (Axelsson, 2008; Mathew, 2011) (leptin, adiponectin, and
retinol-binding protein) and cytokines (resistin, visfatin, interleukin 6, and tumor necrosis factor),
by the adipose tissue.
As with most chronic diseases, demographic variables such as age, sex, ethnicity, and socioeco-
nomic status may affect the incidence and prevalence of CKD (Kiberd, 2006). A study by Hallan et
al. (2006) of over 30,000 men and women each showed that although obesity, smoking, and physi-
cal activity (PA) were associated with CKD, men were less susceptible than women to these risk
factors. However, Krol et al. (2010) recently reported, in a cohort study of over 2500 participants,
that increasing age and comorbidities are more detrimental to men than to women. In the classical,
171
172 Nutrition Therapy for Chronic Kidney Disease
multigenerational Framingham prospective study of over 2500 participants (Fox, 2004), at about
19-years follow-up it was found that cardiovascular risk factors combined with obesity and use of
tobacco were the predictors of new-onset CKD. Further investigation is needed to elucidate demo-
graphic determinants of CKD and related comorbidities such as obesity.
Although exercise programs for those with CKD had been reportedly introduced 30 years ago
(Goldberg et al., 1979), an ongoing concern regarding those with CKD and other chronic conditions
is the lack of regular PA. This is of particular concern with those on regular hemodialysis (HD),
given the added time burden associated with the procedure. An innovative means of surmounting
CKD, a lifestyle hurdle, is the inclusion of PA during HD treatment, otherwise known as intradia-
lytic exercise (Figure 13.1), which is considered safe and beneficial (Davis and Holcombe, 2011).
Several questionnaires have been used to estimate the role of PA in CKD (Johansen et al., 2001),
with the Human Activity Profile correlating best with three-dimensional accelerometers compared
with the Physical Activity Scale for the Elderly and the Medical Outcomes Study Short Form. Gait
length and speed, stair-climbing time and chair-raising time, and overall physical and physiological
functioning (e.g., V02 Max) are examples of various parameters studied in individuals with CKD.
Exercise can contribute to reduced blood pressure and enhanced physical capacity, as recently
observed by Henrique et al. (2010). In this study, 14 patients with CKD who were undergoing HD
were assessed before and after 12 weeks of PA. In a systematic review of 29 clinical trials (Cheema
and Fiatarone Singh, 2005), physical and physiological improvements were noted following aero-
bic training in patients with CKD, who were undergoing HD. Moreover, in a 12-month study of
10 patients on HD, who were free from severe comorbidities, it was noted that moderate exercise
improved aerobic capacity, overall physical functioning, and quality of life (QoL) (Capitanini et al.,
2008). Similar benefits have also been observed in those on peritoneal dialysis (Beasley et al., 1986).
As with nutrition, PA as part of a lifestyle intervention should be individualized (Kutner, 2007) and
promoted as early as possible, as a progressive decline in PA may occur as a consequence of anemia
and skeletal muscle dysfunction. It has been documented that patients on HD may experience a decline
of over 3% in PA each month after dialysis (Johansen et al., 2003). Fatigue can be a chief complaint
of patients with CKD because of anemia and muscle wasting. Therefore, it is imperative to impress
upon them that PA will not aggravate these symptoms but promote health and well-being. Brunier and
Graydon, (1993) looked at the effect of anemia, nonspecific symptoms, and PA on the fatigue level of
43 patients with end-stage renal disease, who were on dialysis. He found that the degree of anemia
FIGURE 13.1 Exercising while on dialysis. (Used with permission from Sylvia Ruttan, patient at Kingston
General Hospital Satellite Dialysis Unit, and Cheryl King-Van Vlack, PhD, associate professor and lead study
investigator on the effects of intradialytic exercise on physical function, dialysis efficacy, and cardiovascular
function, School of Rehabilitation Therapy, Queens University, Ontario.)
174 Nutrition Therapy for Chronic Kidney Disease
was not related to fatigue and that inactivity contributed more to fatigue than the symptoms. Even in
patients with CKD who are on a protein-restricted diet, resistance training has been observed to build
muscle mass and strength (Castaneda et al., 2001). Further, in a cross-sectional study of over 90 men
and women each on HD (median age = 59 years), it was found that factors associated with PA included
age, serum albumin concentration, and physical function (Li and Fan, 2010).
Among the recommended forms of PA, a combination of endurance, flexibility, and strength
training is often encouraged. Bed bicycle ergometers are frequently used in inpatient HD programs
that include a PA component (Kosmadakis et al., 2010). It is believed that exercise programs com-
bined with dialysis may have higher participation rates than outpatient programs, given the habitual,
structured nature of HD. Moreover, no adverse events were reported in a study of exercisers in 200
German dialysis centers, from 1994 to 2004 (Daul et al., 2004). In this study, nearly all participants
were able to do some form of PA. The program included low-intensity endurance activities, training
with a bed bicycle ergometer, gymnastics to increase muscular strength, coordination, and flexibil-
ity, and relaxation techniques. Headley et al. (2002) found that more than 12 weeks of resistance
training improved the strength and functional capacity of patients with CKD who were on HD.
Other PA recommendations for patients with CKD include community-based walking programs,
tai chi, yoga, swimming and/or water exercises, and physical therapy, which can be adopted to meet
appropriate strength-training needs when necessary. Patients undergoing peritoneal dialysis should
not swim in ponds or lakes where catheter-exit infections are possible (Figures 13.2 through 13.5).
To avoid injury and excessive risks associated with PA, it is recommended that patients with
CKD build on activity patterns slowly (Knap et al., 2005). Ten minutes of walking or household
chores is a start. Patients using wheelchairs can try stretching exercises (Figure 13.6). Health care
providers should keep a watch on fluid restrictions and medications. In a recent review of indications
and contraindications of PA in patients with CKD, the authors concluded as follows: While there
FIGURE 13.2 Stretching exercises will help strengthen arm muscles. (From Waxart/Dreamstime.com,
Dreamstime USA Headquarters, Brentwood, TN. With permission.)
Obesity and Physical Activity 175
FIGURE 13.3 Stretching exercises will improve flexibility. (From Waxart/Dreamstime.com, Dreamstime
USA Headquarters, Brentwood, TN. With permission.)
FIGURE 13.4 Exercise that will help improve balance. (From Waxart/Dreamstime.com, Dreamstime USA
Headquarters, Brentwood, TN. With permission.)
176 Nutrition Therapy for Chronic Kidney Disease
FIGURE 13.5 Exercise that will help strengthen hips and thighs and will also improve balance. (From
Waxart/Dreamstime.com, Dreamstime USA Headquarters, Brentwood, TN. With permission.)
FIGURE 13.6 Flexibility exercises recommended for everyone. (From Lisa F. Young/Dreamstime.com,
Dreamstime USA Headquarters, Brentwood, TN. With permission.)
are still no large randomized controlled trials evaluating the survival benefits of exercise, the evi-
dence reviewed justifies regular use of exercise programmes in patients with advanced chronic kid-
ney disease (Kosmadakis et al., 2010). Although data regarding indications and contraindications
are primarily observational and epidemiological, one can conclude with a high degree of certainty
that the potential benefits of regular PA to patients and to the society at large are vast, including
Obesity and Physical Activity 177
better physical and physiological functioning and mobility, improved QoL, and savings in health
care cost. Rare complications of PA have been reported in this population, the most common being
low blood pressure during HD, as per a meta-analysis (Cheema and Fiatarone Singh, 2005). Yet,
surprisingly, PA has not been adopted as a routine component of patient-care programs. In a report
on nephrologists views on exercise for CKD, 95% of the 45 physicians surveyed included physical
inactivity as a risk factor for CKD, over 75% wanted nephrologists to provide counseling on PA, and
74% sought written guidance on PA for their patients (Krause, 2004).
The key message for individuals with chronic conditions is the importance of medical approval
and supervision before making significant changes in PA. Clearly, the more comorbid the condi-
tion, the likelihood of medical risks is higher, and hence the need for close supervision is greater.
A simple talk test can be recommended to patients with CKD to ensure that they are not exer-
cising too vigorously; particularly during lengthy aerobic activities, patients should be able to
carry on a regular conversation. This basic test was closely correlated with VO2, heart rate, and
ventilator threshold on both treadmill and cycle ergometer, in 16 healthy participants (Persinger
et al., 2004). Finally, a lifestyle change that includes PA is highly recommended for patients with
CKD.
diabetes, advanced age, hypertension, and obesity. It also found that obesity was a more robust cor-
relate of microalbuminuria than diabetes and hypertension.
In patients with CKD stages 14, weight loss is generally recommended, as it reduces proteinuria
and glomerular hyperfiltration (Teta, 2010). Notably, urinary albumin excretion is a predictor of
both CKD and CVD. PA can be a protection against discharge of protein into urine, given its role in
enhancing endothelial function. Several treatment pathways may be adapted from the guidelines on
obesity treatment and prevention, put forth by Lau (2007), based on the degree of overweight and
comorbidities. Notably, lifestyle modifications, such as diet, PA, and psychological/emotional sup-
ports, are vital to CKD treatment. PA should be emphasized to increase muscle mass, decrease body
weight, and enhance the overall emotional, physical, and physiological well-being of patients. For
nutrition, total macronutrient energy intake over protein restriction should be encouraged, whenever
possible. Studies of patients who have undergone gastric bypass surgery for morbid obesity have
shown a significant reduction in mortality, owing to major weight loss of the patients (Adams etal.,
2007; Cook et al., 2008). This includes evidence from a long-term trial (Sjostrom et al., 2007) in
which after over 7 years, a reduction of 40% for all-cause mortality, 56% for heart disease, 60%
for cancer, and 92% for diabetes was observed. As focal-segmental glomeruli-sclerosis is related
to obesity, particularly abdominal obesity, bariatric surgery is emerging as a highly effective, long-
term treatment (Alexander et al., 2009).
Several tools are available to assess the potential risks of CKD and other chronic diseases due
to excess body weight. BMI provides a measure of body weight in relation to heightfor most
people, the number correlates with direct measures of body fat, including underwater weighing and
dual-energy x-ray absorptiometry (Garrow et al., 1985; Mei et al., 2002). At BMIs less than 18.5
and greater than 24.9, a robust association with increased mortality exists, as illustrated by a U- or
J-shaped mortality curve (Allison et al., 1997). An adult with a BMI of 30 or more is considered
obese. The National Heart, Lung and Blood Institute has further classified obesity into types IIII,
with type III being an indicator of morbid obesity (BMI > 40) (NHLBI, 2010) (Table 13.1). Online
BMI calculators are available to simplify BMI calculations for patients with CKD and their health
care providers (CDC, 2010).
Waist circumference (WC) is rapidly emerging as the preferred weight-related indicator of CKD.
Although ethnic variation has been reported for WC cut-off values, measures of 35 and 40 in. for
TABLE 13.1
Classification of Overweight and Obesity by BMI, Waist Circumference, and Associated
Disease Risks
Disease Risksa Relative to Normal Weight and Waist Circumference
Men 102 cm ( 40 in.) Men > 102 cm (> 40 in.)
BMI (kg/m2) Obesity Class Women 88 cm ( 35 in.) Women > 88 cm (> 35 in.)
Underweight 18.5
Normalb 18.524.9
Overweight 25.029.9 Increased High
Obesity 30.034.9 I High Very high
35.039.9 II Very high Very high
Morbid obesity 40 III Extremely high Extremely high
Source: National Heart, Lung, and Blood Institutes Obesity Education Initiative: Guidelines on overweight and obesity.
Abbreviations: BMI, body mass index; CVD, cardiovascular disease; CKD, chronic kidney disease.
a Disease risks for type 2 diabetes, hypertension, CVD, and CKD.
b Increased waist circumference can also be a marker for increased risk even in persons of normal weight.
Obesity and Physical Activity 179
women and men, respectively, seem to pose increased risks of chronic diseases. Central or abdomi-
nal fat tissue is generally more metabolically active and readily mobilized to cells, tissues, and
organ systems in which accumulation can cause damage, such as oxidative stress, proinflammation,
and atherosclerotic lesions (Beydoun and Wang, 2007).
As with type 2 diabetes, most of the deaths due to CKD in the United States (Chen et al., 2004)
and, presumably, in other countries are due to CVD, with atherosclerosis being the primary form
of CVD. A robust association exists between metabolic syndrome and type 2 diabetes, which is
often a precursor to CKD (USRDS, 2003). Metabolic syndrome includes a cluster of cardiometabolic
conditions, including dyslipidemia, insulin resistance, hypertension, hyperglycemia, and abdominal
obesity. Nearly one-fourth of Americans over 20 years have this syndromeexcess weight being the
main cause of these symptoms (Wassink et al., 2008). It was found that WC was a better prognostic
marker for mortality than BMI in a prospective cohort of 993 kidney transplant recipients (Kovesdy
et al., 2010). Moreover, in a representative sample of over 3000 participants, Noori et al. (2009) con-
cluded that WC was a more important determinant of CKD in adults than waist-to-hip ratio and BMI.
Regarding physiological implications, the U.S. NHANES findings from 1998 to 1994 (Guarnieri
et al., 2010) revealed that participants with 3, 4, and 5 aspects of the metabolic syndrome had
increased odds of 1.62, 2.45, and 3.19, respectively, for microalbuminuriacompared to those with
0 or 1 aspects. These associations were independent of sex, age, race, or ethnicity. This creates a
vicious cycle because increased renal damage may aggravate features of the metabolic syndrome,
including insulin resistance and hypertension. Therefore, addressing the interactions between CKD,
obesity, and metabolic syndrome is of utmost importance.
As physiological benefits are evident with as little as 5%10% reduction in on total body weight,
long-term weight management is crucial for CKD. The challenge is to address long-term weight
management in the treatment of chronic diseases. Innovative means of increasing PA are warranted.
The overwhelming population-based evidence of the benefit of the use of the pedometer in weight
management (Bravata et al., 2007) also appears relevant to the population with CKD. The practice
goal of 10,000 steps a day provides a ready, teachable concept in patient care. Nowicki et al. (2010)
observed a decrease in BMI and blood pressure in patients with CKD with an increase in the use of
the pedometer. Zamojska et al. (2006) further noted that simple pedometer use can correlate with
key clinical and biochemical parameters in this population. In this instance, the less physically
active participants had lower concentrations of albumin and increased anemia.
13.7 CONCLUSIONS
It is highly likely that PA contributes to reduced morbidity and mortality and increased QoL in
patients with CKD, with weight management being central to these health benefits. PA guidelines
180 Nutrition Therapy for Chronic Kidney Disease
TABLE 13.2
Online Resources
Physical Activity Guidelines, U.S. National Kidney Foundation: Staying Fit with Kidney Disease (www.Kidney.
Department of Health and Human org/atoz/content/stayfit.cfm)
Services (HHS) (http://www.health.gov/
paguidelines)
Life Options (www.lifeoptions.org) healthfinder: A Guide to Reliable Health Information on Physical Activity
and Other Topics, HHS (http://www.healthfinder.gov)
Office of Disease Prevention and Health Centers for Disease Control and Prevention (CDC), HHS (http://www.cdc.
Promotion, HHS (http://odphp.osophs. gov/physicalactivity)
dhhs.gov)
Food and Nutrition Service, USDA (http:// CDC Information about Preventing Falls in Older Adults, HHS (http://www.
www.fns.usda.gov/fns) cdc.gov/ncipc/factsheets/adultfalls.htm)
U.S. Department of Health and Human National Institute on Aging Exercise Guide, HHS (http://www.nia.nih.gov/
Services Online (www.health.gov/ HealthInformation/Publications/ExerciseGuide/chapter01.htm)
PAGuidelines)
for patients with CKD are generally congruent with those for the general population, with an impor-
tant caution about starting and progressing PA slowly and requiring patients to be under the super-
vision of a health care provider. As with other robust behavior change modalities, it is essential
to provide small, measurable, and realistic recommendations of PA and weight management for
patients with CKD. Multidisciplinary care (Cueto-Manzano et al., 2010; Johansen, 2005)includ-
ing primary care physicians, dietitians, nurses, and social workersalong with self-help/support
groups is recommended, for which there are many online resources available (Table 13.2).
In a recent article, Painter (2009) commented, although there is robust evidence that these [CKD]
patients benefit from regular exercise training and/or increasing physical activity, the nephrology
community has not adopted recommendations and encouragement for physical activity as a part of
the routine care plan. Given the high likelihood of comorbid conditions, national PA guidelines
that ideally align with those for other chronic diseases are warranted. Moreover, a multidimensional
approach for treatment and prevention of chronic diseases is recommended. Qualitative (Jennette
et al., 2010) and quantitative (Nikolas et al., 2004) data support the heightened need for increased
knowledge and awareness of risk factors associated with CKD, including type 2 diabetes, family
history, and hypertension. Further focus is needed on innovations in this area and on community-
based initiatives such as education and health screening, improved measures of body composition
and energy expenditure, and better understanding of the mechanisms underlying the relationship
between CKD and obesity.
REFERENCES
Adams, T., Gess, R., Smith, S., et al. 2007. Long-term mortality after gastric bypass surgery. N Engl J Med.
357(8):753761.
Agarwal, R., Bills, J., Light, R. 2010. Diagnosing obesity by body mass index in chronic kidney disease: An
explanation of the obesity paradox? Hypertension 56(5):893900. Epub 2010 September 27.
Alexander, J., Coodman, H., Hawver, L., et al. 2009. Improvement and stabilization of chronic kidney disease
after gastric bypass. Surg Obes Relat Dis. 5(2):237241. Epub 2008 August 27.
Allison, D., Myles, S., Moonseong, H., et al. 1997. Hypothesis concerning the U-shaped relation between body
mass index and mortality. Am J Epidem. 146:339349.
Axelsson, J. 2008. Obesity in chronic kidney disease: Good or bad? Blood Purif. 26(1):2329. Epub 2008
January 10.
Beasley, C., Smith, D., Neale, T. 1986. Exercise capacity in chronic renal failure patients managed by continu-
ous ambulatory peritoneal dialysis. Aust NZ J Med. 16:510.
Obesity and Physical Activity 181
Beddu, S, Baird, B., Zitterkoph, J., et al. 2009. Physical activity and mortality in chronic kidney disease
(NHANES III). Clin J Am Soc Nephrol. 4:19011906.
Bello, A., Peters, J., Wight, J., et al. 2010. The kidney evaluation and awareness program in Sheffield (KEAPS):
A community-based screening for microalbuminuria in a British population. Nephron Clin Pract.
116(2):c95c103. Epub 2010 May 21.
Beydoun, M. and Wang, Y. 2007. Gender-ethnic disparity in BMI and waist circumference shifts in US adults.
Obesity 17(1):169176.
Bravata, D., Smith-Spangler, C., Sundaram, V., et al. 2007. Using pedometers to increase physical activity and
improve health: A systematic review. JAMA 21;298(19):2296304.
Brenner, I. and Brohart, K. 2008. Weekly energy expenditure and quality of life in hemodialysis patients.
CANNT J. 18(4):3640.
Brodin, E., Ljungman, S., Hedberg, M., et al. 2001. Physical activity, muscle performance and quality of life in
patients treated with peritoneal dialysis. Scan J Urol Nephrol. 35(1):7178.
Brunier, G. and Graydon, J. 1993. The influence of PA on fatigue in pts with ESRD on dialysis. ANNA J.
20(4):457461. Discussion 462, 521.
Canadas Physical Activity Guide for Healthy Living. 2010. Public Health Agency of Canada and Canadian
Society for Exercise Physiology. Online: www.paguide.com (accessed December 2010).
Capitanini, A., Cupisti, A., Mochi, N., et al. 2008. Effects of exercise training on exercise aerobic capacity and
quality of life in hemodialysis patients. J Nephrol. 21(5):738743.
Castaneda, C., Gordon, P., Uhlin, K., et al. 2001. Resistance training to counteract the catabolism of a low-
protein diet in patients with chronic renal insufficiency. Ann Intern Med. 135:965976.
CDC. 2010. Online ref for BMI calculator. Online: www.cdc.gov/healthyweight/assessing/bmi/adult_bmi/eng-
lish_bmi_calculator/bmi_calculator.html (accessed December 2010).
Cheema, B. and Fiatarone Singh, M. 2005. Exercise training in patients receiving maintenance hemodialysis:
A systematic review of clinical trials. Am J Nephrol. 25:352364.
Chen, J., Muntner, P., Hamm, L., et al. 2004. The metabolic syndrome and chronic kidney disease in US adults.
Ann Intern Med. 140:167174.
Cook, S., MacLaughlin, H., Macdougall, I. 2008. A structured weight management programme can achieve
improved functional ability and significant weight loss in obese patients with chronic kidney disease.
Nephrol Dial Transplant. 23:263268.
Corpeleijn, E., Bakker, S., Stolk, R. 2009. Obesity and impaired renal function: Potential for lifestyle interven-
tion? Eur J Epidemiol. 24(6):275280. Epub 2009 May 7.
Cueto-Manzano, A., Martinez-Ramirez, H., Cortes-Sanabria, L. 2010. Management of chronic kid-
ney disease: Primary health-care setting, self-care and multidisciplinary approach. Clin Nephrol.
Sup;74(S1):99104.
Daul, A., Schafers, R., Daul, K., et al. 2004. Exercise during hemodialysis. Clin Nephrol. 61(Suppl1):
S26S30.
Davis, J. and Holcombe, J. 2011. Intradialytic exercise: A pilot program. Dialysis Transplant. 40(6):258260.
Ejerblad, E., Fored, C., Lindblad, P., et al. 2006. Obesity and risk for chronic renal failure. J Am Soc Nephrol.
17:16951702.
Eknoyan, G. 2006. A history of obesity, or how what was good became ugly and then bad. Adv Chronic Kidney
Dis. 13(4):421427.
Fox, C., Larson, M., Leip, E., et al. 2004. Predictors of new-onset kidney disease in a community-based popula-
tion. JAMA 291:844850.
Garrow, J. and Webster, J. 1985. Quetelets index (W/H2) as a measure of fatness. Int J Obes. 9:147153.
Goldberg, A., Hagberg, J., Delmez, J., et al. 1979. Exercise training improves abnormal lipid and carbohydrate
metabolism in hemodialysis patients. Trans Am Soc Artif Intern Organs. 25:431437.
Guarnieri, G., Zanetti, M., Vinci, P., et al. 2010. Metabolic syndrome and chronic kidney disease. J Ren Nutr.
20(5 Suppl):S19S23.
Hallan, S., de Mutsert, R., Carlsen, S., et al. 2006. Obesity, smoking and physical inactivity as risk factors for
CKD: Are men more vulnerable? Am J Kidney Dis. 47(3):396405.
Headley, S., Germain, M., Mailloux, P., et al. 2002. Resistance training improves strength and functional mea-
sures in patients with end-stage renal disease. Am J Kidney Dis. 40(2):355364.
Heber, D. 2010. An integrative view of obesity. Am J Clin Nutr. 9(suppl):280S283S.
Henrique, D., Reboredo Mde, M., Chaoubah, A., et al. 2010. Aerobic exercise improves physical capacity in
patients under chronic hemodialysis. Arq Bras Cardiol. 94(6):823828.
Hsieh, R., Lee, W., Huang, H., et al. 2007. Quality of life and its correlates in ambulatory hemodialysis patients.
J Nephrol. 20:731738.
182 Nutrition Therapy for Chronic Kidney Disease
Jennette, C., Vupputuri, S., Hogan, S., et al. 2010. Community perspectives on kidney disease and health pro-
motion from at-risk populations in rural North Carolina, USA. Rural Remote Health. 10:1388. Online:
www.rrh.org.au
Johansen, K., Kaysen, G., Young, B., et al. 2003. Longitudinal study of nutritional status, body composition and
physical function in hemodialysis patients. Am J Clin Nutr. 77:842846.
Johansen, K., Painter, P., Kent-Braun, J,. et al. 2001. Validation of questionnaires to estimate physical activity
and functioning in end-stage renal disease. Kidney Int. 59(3):11211127.
Johansen, K. 2005. Exercise and CKD: Current recommendations. Sports Med. 35(6):485499.
Kalantar-Zadeh, K., Streja, E., Kovedsky, C., et al. 2010. The obesity paradox and mortality associated
with surrogates of body size and muscle mass in patients receiving hemodialysis. Mayo Clin Proc.
85(11):9911001.
Kiberd, B. 2006. The chronic kidney disease epidemic: Stepping back and looking forward. J Am Soc Nephrol.
17:29672973.
Knap, B., Butorvic-Ponikvar, J., Ponikvar, R., et al. 2005. Regular exercise as part of treatment for patients with
end-stage renal disease. Ther Apher Dial. 9(3):211213.
Kosmadakis, G., Bevington, A., Smith, A., et al. 2010. Physical exercise in patients with severe kidney disease.
Nephron Clin Pract. 115:c7c16.
Kouldi, E., Lacovides, A., Iordanidis, P. 1997. Exercise renal rehabilitation program: Psychosocial effects.
Nephron. 77:152158.
Kovesdy, C., Czira, M., Rudas, A., et al. 2010. Body mass index, waist circumference and mortality in kidney
transplant recipients. Am J Transplant. 10(12):26442651. Epub 2010 November 18.
Krause, R. 2004. WGRR-European Working Group on Renal Rehabilitation and Exercise Physiology.
Nephrologists view on exercise training in chronic kidney disease (results of the questionnaire at the
WCN 2003). Clin Nephrol. 61(Suppl 1):S2S4.
Krol, E., Rutkowski, B., Czarniak, P., et al. 2010. Aging or comorbid conditionswhat is the main cause of
kidney damage? J Nephrol. 23(4):444452.
Kutner, N., Zhang, R., Mclellan, W. 2000. Patient-reported quality of life early in dialysis treatment: Effects
associated with usual exercise activity. Nephrol Nurs J. 27(4):357367.
Kutner, N. 2007. How can exercise be incorporated into the routine care of patients on dialysis? Int Urol
Nephrol. 39(4):12811285.
Lastra, G., Manrique, C., Sowers, J. 2006. Obesity, cardiometabolic syndrome and chronic kidney disease: The
weight of the evidence. Adv Chronic Kidney Dis. 13(4):365373.
Lau, D. 2007. Obesity Canada Clinical Practice Guidelines Steering Committee and Expert Panel. Synopsis of
the 2006 Canadian clinical practice guidelines on the management and prevention of obesity in adults
and children. CMAJ April 10;176(8):11031106.
Li, M. and Fan, X. 2010. Patients having hemodialysis: Physical activity and associated factors. J Adv Nurs.
66(6):13381345. Epub 2010 April 1.
Mathew, A., Okada, S., Sharma, K. 2011. Obesity related kidney disease. Curr Diabetes Rev. 7(1):4149.
McClellan, W., Abramson, J., Newsome, B., et al. 2010. Physical and psychological burden of CKD among
older adults. Am J Nephrol. 31(4):309317. Epub 2010 February 13.
Mei, Z., Grummer-Strawn, L., Pietrobelli, A., et al. 2002. Validity of body mass index compared with other
body-composition screening indexes for the assessment of body fatness in children and adolescents. Am
J Clin Nutr. 75(6):978985.
Mokdad, A., Marks, J., Stroup, D., et al. 2004. Actual causes of death in the United States, 2000. JAMA
29(10):12381245.
Monteon, F., Laidlaw, S., Shaib, J., et al. 1986. Energy expenditure in patients with chronic renal failure. Kidney
Int. 30(5):741747.
Navaneethan, S., Yehnert, H., Moustarah, F., et al. 2009. Weight loss interventions in chronic kidney disease:
Asystematic review and meta-analysis. Clin J Am Soc Nephrol. 4:15651574.
NHLBI obesity guidelines. 2010. Online. http://www.nhlbi.nih.gov/guidelines/obesity/bmi_tbl.htm (accessed
July 2011).
Nikolas, T., Gershon, F., Opotowsky, A., et al. 2004. Awareness of kidney disease in the US population:
Findings from the National Health and Nutrition Examination Survey (NHANES) 1999 to 2000. Am J
Kidney Dis. 44(2):185197.
Noori, N., Hosseinpanah, F., Nasiri, A., et al. 2009. Comparison of overall obesity and abdominal adiposity in
predicting chronic kidney disease incidence among adults. J Ren Nutr. 19(3):228237. Epub March 3,
2009.
Obesity and Physical Activity 183
Nowicki, M., Murlikiewicz, K., Jagodzinka, M. 2010. Pedometers as a means to increase spontaneous physical
activity in chronic hemodialysis patients. J Nephrol. 23(3):297305.
Obermayr, R., Temml, C., Gutjahr, G., et al. 2009. Body mass index modifies the risk of cardiovascular death in
proteinuric chronic kidney disease. Nephrol Dial Transplant. 24(8):24212428. Epub 2009 February 24.
Ouzoni, S., Kouidi, E., Sioulis, A., et al. 2009. Effects of intradialytic exercise training on health-related quality
of life indices in haemodialysis patients. Clin Rehabil. 23:5363.
Painter, P. 2009. Implementing exercise: What do we know? Where do we go? Adv Chronic Kidney Dis.
16(6):536544.
Persinger, R., Foster, C., Gibson, M., et al. 2004. Consistency of the talk test for exercise prescription. Med Sci
Sports Exerc. 36(9):16321636.
Sjostrom, L., Narbo, K., Sjostrom, C., et al. 2007. Effects of bariatric surgery on mortality in Swedish obese
subjects. N Engl J Med. 357(8):741752.
Soni, R., Weisbord, S., Unruh, M. 2010. Health-related quality of life outcomes in chronic kidney disease. Curr
Opin Nephrol Hypertens. 19(2):153159.
Stack, A. and Murthy, B. 2008. Exercise and limitations in physical activity levels among new dialysis in the
United States: An epidemiologic study. Ann Epidemiol. 18(12):880888.
Stenvinkel, P. 2010. Chronic kidney disease: A public priority and harbinger of premature cardiovascular dis-
ease. J Intern Med. 268(5):456467.
Stolic, R. 2010. Obesity in renal failure: Health or disease? Med Hypotheses. 75(6):497500. Epub 2010 July
24.
Tackling Obesity: The evidence and the uncertainty. The UK Foresight Project. 2007. Online: www.bis.gov.uk/
assets/bispartners/docs/obesity/obesity_final_part2.pdf (accessed December 2010).
Teta, D. 2010. Weight loss in obese patients with chronic kidney disease: Who and how? J Ren Care.
36(Suppl1):163171.
Ting, S., Nair, H., Ching, I., et al. 2009. Overweight, obesity and chronic kidney disease. Nephron Clin Pract.
112c:c121c127.
U.S. Department of Health and Human Services (USDHHS). 2008. Physical activity guidelines for Americans
[electronic resource]: Be active your way: A fact sheet for adults, Washington, D.C. Online: www.health.
gov/PAGuidelines (accessed December 2010).
U.S. Renal Data System (USRDS). 2003. 2003 Annual Data Report: Atlas of End Stage Renal Disease in the
United States. Bethesda, MD: National Institutes of Health, National Institute of Diabetes and Digestive
and Kidney Diseases.
Wang, Y., Chen, X., Song, Y., et al. 2008. Association between obesity and kidney disease: A systematic review
and meta-analysis. Kidney Int. 73(1):1933. Epub 2007 October 10.
Wassink, A., Van Der Graaf, Y., Soedamah-Muthu, S., et al. 2008. Smart Study Group. Metabolic syndrome and
incidence of type 2 diabetes in patients with manifest vascular disease. Diab Vasc Kid Res. 5(2):114122.
Zamojska, S., Szklarek, M., Niewodniczy, M., et al. 2006. Correlates of habitual physical activity in chronic
hemodialysis patients. Nephrol Dial Transplant. 21:13231327.
14 Chronic Kidney Disease
and Mineral and Bone
Disorder Management
C.J. Parris
Columbia Nephrology
Beth Parris
Blue Cross Blue Shield of South Carolina
CONTENTS
14.1 Introduction........................................................................................................................... 185
14.2 Phosphorus............................................................................................................................. 186
14.3 Calcium.................................................................................................................................. 188
14.4 Parathyroid Hormone............................................................................................................ 189
14.5 Vitamin D.............................................................................................................................. 189
14.6 Summary............................................................................................................................... 193
References....................................................................................................................................... 193
14.1 INTRODUCTION
This chapter discusses chronic kidney disease and mineral bone disorder (CKDMBD) and the role
it plays in the increased incidence of cardiovascular morbidity and mortality in CKD. Just how great
is the risk? After adjusting for age, race, and gender, cardiovascular disease (CVD) mortality rates in
patients with CKD Stage 5 are 1020 times those of the general population (Foley et al., 1998). Most
patients with advanced CKD present with vitamin D deficiency, secondary hyperparathyroidism
(SHPT), hypertension, insulin resistance, vascular calcifications, and dyslipidemia. These comor-
bidities may start early in Stage 3 CKD and, though they seem dissimilar, have more in common
than is apparent at first review (Andress, 2005; Becker et al., 2005; Elder, 2002; Kramer et al., 2005).
As renal function declines, the body tries to maintain calcium homeostasis through adaptive
and compensatory mechanisms. These work well up to a point, but as CKD progresses, the com-
pensatory mechanisms begin to fail. There is a decline in urinary phosphorus excretion leading
to increased serum phosphorus, which stimulates increased fibroblast growth factor 23 (FGF-23),
causing a reduction in active vitamin D, subsequent elevation of parathyroid hormone (PTH), and
reduced urinary calcium excretion leading to calcium imbalance. This maladaptive dysregulation
leads to elevated phosphorus, worsening SHPT and, if untreated, calcium overload, which contrib-
utes to vascular calcifications and increased cardiovascular (CV) morbidity and mortality (Gutierrez
et al., 2005; Kalantar-Zadeh et al., 2010; Seiler et al., 2009; Figure 14.1).
Since 1989, the National Kidney Foundation Dialysis Outcomes Quality Initiative (K/DOQI)
guidelines have guided the treatment of metabolic bone disorder in dialysis patients. In 2003,
the scope of the NKF guidelines was expanded by the K/DOQI. The more recent guidelines
185
186 Nutrition Therapy for Chronic Kidney Disease
FIGURE 14.1 Progression of bone disease. (Courtesy of Shaun Riffle, University of South Carolina School
of Medicine, Columbia, SC.)
revolutionized the care of CKD patients because they not only included recommendations for the
dialysis population, but for the first time also made recommendations for all patients with CKD.
The guidelines stressed prevention and early diagnosis and continued to focus on treatment. The
new guidelines also defined the five stages of CKD and started to shed more light on the comor-
bidities of CKD. The bone and mineral section of the guidelines included specific recommenda-
tions for the prevention and treatment of SHPT (NKF, 2002).
In 2009, the Kidney Disease Improving Global Outcome (KDIGO) CKD-MBD Guidelines
recommended changes to the KDOQI (2003) bone guidelines placing more emphasis on trending
mineral and PTH values; attempting to control PTH, phosphorus, and calcium more tightly within
the normal range for CKD Stages 35; and expanding the recommended PTH range for dialysis
patients to 29 times normal (KDIGO, 2009). With the release of KDOQI Commentary on KDIGO
in February 2010, the guidelines became the accepted standard of care in the United States (Kasiske
et al., 2010; Uhlig et al., 2010).
A new system of bundling charges became effective in 2011 with the Centers for Medicare
and Medicaid Services (CMS) prospective payment system for the dialysis population. Dialysis
companies will no longer be able to charge separately for the IV drugs or for oral drugs with IV
equivalents that are used to treat CKDMBD. Oral medications without IV equivalents, such as
phosphorus binders and calcimimetics, will come into the bundle in 2014. Exactly what effect this
will have on quality outcomes remains to be seen (CMS, 2008).
14.2 PHOSPHORUS
Phosphorus is one of the most abundant minerals in the human body, second only to calcium. It
is stored in bones, teeth, DNA, and cell membranes throughout the body. Inorganic phosphorus
is critical for skeletal development and the conversion of food to energy. Phosphorus helps with
muscle contraction, nerve conduction, and kidney function. Phosphorus deficiency does not nor-
mally occur except with the use of certain products, such as calcium, sevelemer, and antacids
that contain aluminum or magnesium, which prevent phosphorus absorption by binding it in the
gut. Most phosphorus is intracellular, but a change in pH and serum glucose can cause it to shift
in and out of cells, changing the level that is measured without changing the total body phos-
phorus (KDIGO, 2009). Approximately 700 mg of phosphorus is present in the average adult, of
which 85% is contained in bone in the form of hydroxyapatite. Fifteen percent of the extracellular
Chronic Kidney Disease and Mineral and Bone Disorder Management 187
phosphorus is circulating and is measured when a serum phosphorus level is obtained. The
Recommended Daily Allowance (RDA) for phosphorus is about 1000 mg for adults, although
the average dietary intake is between 800 and 1500 mg/day. Approximately 65% of ingested
phosphorus is absorbed in the small intestine, and approximately 200 mg is exchanged between
the extracellular pool and bone. The kidneys excrete about 900 mg of excess phosphorus a day.
Kidney excretion of phosphorus is the primary method of maintaining phosphorus homeostasis
(Brenner, 2008). Foods high in phosphorus are the protein-rich foods like meat, dairy products,
and legumes. Approximately 70% of the phosphorus in meat and dairy products is absorbed. Beef
and chicken contain about 8 mg phosphorus per gram of protein, much less than low-fat milk,
which has 28 mg phosphorus per gram of protein. Balancing a diet containing high biologic value
protein, while adhering to a low-phosphorus diet, is difficult at best. Processed meats and cheeses
often contain phosphorus additives, which are noted on the list of ingredients but not on the nutri-
tion label. Educating patients to read the list of ingredients will help them to learn which foods to
avoid and to make better dietary choices (USDA, 2001).
Recent studies used in the formulation of the KDIGO CKD-MBD guidelines suggest that dialysis
patients have higher mortality rates with even a modest elevation in phosphorus. One study looked
at the association between higher phosphorus levels and mortality. Of the patients who had phos-
phorus levels maintained within the KDOQI guidelines, 72% had an increased risk of mortality. A
linear relationship was observed between serum phosphorus and mortality, such that with each 0.5
mg/dL increase in phosphorus, there was a corresponding increase in mortality. When phosphorus
levels reached 3.5 mg/dL or above, a statistically significant increase in mortality was observed. A 1
mg/dL increase in serum phosphorus was associated with a significant 35% increased risk for acute
myocardial infarction (MI) and a 28% increased risk for death or nonfatal MI. This study clearly
demonstrated that for dialysis patients, increased phosphorus is associated with an increased risk of
cardiovascular morbidity and mortality (Kestenbaum et al., 2005).
It appears that even in the non-CKD population, the risks associated with elevated phosphorus
are higher as well. To evaluate this effect, the Framingham Offspring Study evaluated the relation-
ship of serum phosphorus and calcium to the incidence of CVD. Participants were excluded from
the analysis if they had CVD or CKD. The primary outcomes were MI, angina, cerebrovascular
events, peripheral vascular disease, and congestive heart failure. The analysis revealed that partici-
pants with high serum phosphorus levels were associated with an increased risk of CVD (Dhingra
et al., 2007). In a second study of non-CKD patients with a recent MI, higher baseline serum phos-
phorus was associated with a significantly greater risk of MI and death (Tonelli et al., 2005).
To prevent the CKD comorbidities associated with high phosphorus, it is recommended that
patients follow a low-phosphorus diet. Though controversial, a low-protein diet of 0.60.8 g/kg/day
may also slow the progression of kidney disease, reduce proteinuria, and keep serum phosphorus
within normal limits (Mitch, 2005). Once the patient has progressed to dialysis, a higher-protein
diet is recommended. It is difficult to increase protein intake and at the same time keep phosphorus
intake low.
KDIGO and KDOQI Commentary on KDIGO suggest more emphasis should be placed on
maintaining phosphorus toward the normal or reference range. The 2003 KDOQI Guidelines
suggested that a phosphorus range of 3.55.5 mg/dL was optimal, but there is ample evidence,
even in the non-CKD population, to suggest that tighter phosphorus control would be benefi-
cial. Data from several large dialysis populations that compared patients with serum phosphorus
6.5mg/dL to patients with serum phosphorus > 6.5 mg/dL showed that the higher phosphorus
group were at a significantly increased risk of mortality from coronary artery disease (CAD) and
sudden death compared to the group with lower phosphorus levels (Ganesh et al., 2001). Another
analysis of 40,538 hemodialysis patients found that serum phosphorus levels less than 3 mg/dL
and more than 5 mg/dL were associated with increased relative risk of death (Block et al., 2004).
Another analysis of 58,000 hemodialysis patients confirmed the increased risk for death associ-
ated with high serum phosphorus, but it did not find the same association with low phosphorus
188 Nutrition Therapy for Chronic Kidney Disease
after controlling for malnutrition, inflammation, and cachexia syndrome. Therefore, the KDIGO
Guidelines do not suggest keeping phosphorus above 3.5 mg/dL as the 2003 KDOQI Guidelines
recommended (Kalantar-Zadeh et al., 2006).
The relationship between elevated phosphorus and increased risk of death in the dialysis popu-
lation is well established. What other modifiable risk factors contribute to vascular calcifications,
increased CV events, and death? Actually, an increase in mortality is associated with all mineral
and bone parameters, including phosphorus, calcium, and PTH, although the highest mortality is
associated with phosphorus (Block et al., 2004). It is important to recognize that diet is not the only
source of phosphorus: an elevated PTH can cause resorption of phosphorus and calcium from bone.
As CKD progresses, bones increase the production of FGF-23 to try to keep serum phosphorus in the
normal range, causing phosphaturia. FGF-23 also suppresses activation of vitamin D by the kidney
and contributes to the development of SHPT. Another ominous sign is that dialysis patients with the
highest FGF-23 have the highest mortality independent of PTH, calcium, and phosphorus (KDIGO,
2009).
14.3 CALCIUM
The measured serum calcium is a poor reflection of total body calcium. Only 1% of total body cal-
cium is measurable in the serum; the rest is stored in bone. Only ionized calcium, generally 40%
50% of total serum calcium, is physiologically active. Nonionized calcium is bound to albumin and
is not physiologically active. In the presence of low serum albumin, there is an increase in ionized
calcium relative to total calcium; thus, total serum calcium may underestimate the active serum
calcium. A formula for estimating corrected calcium is to add 0.8 mg/dL to the serum calcium for
every 1 g decrease in serum albumin below 4 g/dL (KDIGO, 2009).
Serum calcium effectively determines the rate of PTH secretion, since with a slight reduction in
serum calcium there is a prompt increase in PTH secretion occurring within a matter of seconds.
The rise occurs as a result of preformed PTH being released from stored puvules in the parathyroid
glands. If PTH secretion is not effective at maintaining the blood calcium level, increased PTH
synthesis occurs over several hours to days. The increased PTH synthesis is mediated through the
parathyroid calcium and vitamin D receptors. As CKD progresses, active vitamin D levels fall and
further stimulate PTH secretion. PTH causes calcium and phosphorus resorption from bone and
reduces calcium excretion by the kidney. PTH then causes increased activation of vitamin D, which
increases absorption of calcium and phosphorus in the gut. The net result of increased PTH secre-
tion is an increase in serum calcium (Andress, 2006; Brown et al., 1999; Rodriguez et al., 2006).
In CKD 4 and 5, serum calcium levels decline as active vitamin D levels fall. This results in
decreased intestinal absorption of calcium in the gut (Hsu, 2007). By the time most patients reach
dialysis, they lack adequate kidney function to excrete calcium and subsequently end up in a positive
calcium balance and hypercalcemia (Friis et al., 1968; Popovtzer et al., 1969). Hypercalcemia, more
so than hypocalcemia, is associated with increased mortality in the dialysis population. Using a
multivariant analysis of a large dialysis population, it was found that the association between serum
calcium and relative risk of death was linear with lower risk at lower calcium concentrations. The
risk of death with higher calcium was independent of PTH or phosphorus (Kalantar-Zadeh etal.,
2006).
The 2003 KDOQI Guidelines called for maintaining the serum calcium in the range of 8.49.5
mg/dL, but with the newer 2009 KDIGO and 2010 KDOQI Commentary on KDIGO the stringent
control of calcium at the lower end of the normal range has been relaxed and it is now recommended
to maintain calcium within the normal or reference range for the lab. Calcium levels that are higher
than normal are associated with an increased risk of vascular calcification and result in increased
morbidity and mortality. When calcification occurs or when hypercalcemia recurs, care should be
exercised to maintain the calcium in the reference range, and the use of calcium-containing phos-
phorus binders should be avoided (Kasiske et al., 2010).
Chronic Kidney Disease and Mineral and Bone Disorder Management 189
14.5 VITAMIN D
Vitamin D parent compound is derived from dietary sources or produced in the skin from exposure
to heat and sunlight. The compound is converted in the liver to 25-hydroxyvitamin D, ergocalcif-
erol. The last step in activating vitamin D to 1, 25 dihydroxyvitamin D occurs in the kidney (Drueke
et al., 2006). Active vitamin D then travels throughout the body where it binds to the vitamin D
receptors on target organs (Dusso et al., 2005). In 1984, Dr. Slatopolsky demonstrated the ability of
the first-generation active vitamin D to suppress PTH in uremic patients; unfortunately, his study
also demonstrated that the vitamin D caused a significant increase in serum calcium. The rise in
calcium prompted researchers to work to develop new vitamin D analogs that suppress PTH without
raising serum calcium (Slatopolsky et al., 1984). Since then, active vitamin D has been used as the
mainstay of therapy to try to prevent SHPT. Active vitamin D prevents parathyroid gland hyperpla-
sia, suppresses PTH synthesis and secretion, upregulates vitamin D receptors and calcium-sensing
receptors in parathyroid gland, promotes mineral homeostasis by increased absorption of calcium
and phosphorus, and helps to maintain normal bone formation (Andress, 2005).
The kidney is not alone in producing active vitamin D; other organs such as lung, colon, prostate,
and breast have the 1- hydroxylase enzyme to convert ergocalciferol to active vitamin D for local
use within the organ. It is important to realize that this locally produced active vitamin D does not
190 Nutrition Therapy for Chronic Kidney Disease
replace the loss of kidney-activated vitamin D to prevent SHPT as CKD progresses (Drueke et al.,
2006). Conversely, giving active vitamin D to treat SHPT does not replace all of the vitamin D
needs of the body because the level of active vitamin D obtained in treating SHPT is too low to meet
the needs of all the tissues that require it. An ergocalciferol level of at least 30 ng/mL is needed to
accomplish this (Goodman and Quarles, 2006).
It is now understood that in many cases, treatment with ergocalciferol does not prevent SHPT in
the CKD population. To assess the effect of treatment, a prospective, nonrandomized observational
study was performed in vitamin D-deficient patients with stage 3 and 4 CKD. Fifty-two patients
with CKD Stage 3 or 4 with vitamin D deficiency and elevated PTH received ergocalciferol. The
results revealed that ergocalciferol normalized 25 vitamin D levels in all patients and the median
decline in PTH was 13.1% in Stage 3 but only 2.0% in Stage 4. This suggests that ergocalciferol may
be a reasonable initial therapy for vitamin D deficiency with elevated PTH levels in Stage 3 CKD;
however, it does not appear to have significant benefits in CKD Stage 4 (Zisman et al., 2007). The
decline in active vitamin D occurs much earlier than we previously thought. The decline begins in
Stage 2 CKD and is near the low end of the normal range by the time patients reach Stage 3. This
helps to explain why it is common to see early signs of SHPT in CKD Stage 3. Throughout the early
stages of CKD, calcium and phosphorus remain normal or near normal, and do not serve as good
markers for developing SHPT. In late Stage 3 CKD, phosphorus and calcium start to become abnor-
mal and SHPT rates are much higher. By CKD Stage 45, the majority of the patients have SHPT
along with abnormal calcium and phosphorus levels (Levin et al., 2007).
CVD may be improved with active vitamin D supplementation, which inhibits inflammatory
markers, modulates immune responses, downregulates renin, stimulates cardiomyocyte remodel-
ing, regulates markers of cardiomyocyte hypertrophy, and may improve LVH in patients undergoing
dialysis. Based on these observations, it has been hypothesized that vitamin D may improve CV
outcomes including reduced incidence of heart failure, atherosclerosis, and myocardial hypertrophy
and, possibly, decreased overall morbidity and mortality (Li et al., 2002; Mathieu and Adornin,
2002; Park et al., 1999; Timms et al., 2002).
A study of 50 dialysis patients, half of whom received active vitamin D after hemodialysis,
revealed that the patients treated with active vitamin D had regression of myocardial hypertro-
phy and a reduction in risk factors for sudden cardiac death. Active vitamin D may be a promis-
ing treatment for reducing the rate of sudden cardiac death in the dialysis population (Kim et al.,
2006). The fact that vitamin D receptors are ubiquitous throughout the body may explain why so
TABLE 14.1
Target Ranges for Treatment of CKDMBD
Stage 3, 4, and 5 Predialysis Stage 5 Dialysis
Calcium Maintain within normal (KDIGO & Maintain within normal (KDIGO). 8.49.5 mg/dL or
KDOQI) 2.12.375 mmol/L (KDOQI)
Phosphorus Maintain within normal (KDIGO) 2.74.6 Maintain toward normal (KDIGO) 3.55.5 mg/dL or
mg/dL or 0.871.49 mmol/L (KDOQI) 1.131.78 mmol/L (KDOQI)
TABLE 14.2
Target Ranges for Initiating Treatment for intact parathyroid hormone
(iPTH)
Stage 3 > Upper limit of normal (KDIGO)3570 pg/mL (KDOQI)
Stage 4 > Upper limit of normal (KDIGO)70110 pg/mL (KDOQI)
Stage 5 > Upper limit of normal (KDIGO)150300 pg/mL (KDOQI)
Stage 5D 29 times upper limit of normal (KDIGO)150300 pg/mL (KDOQI)
Chronic Kidney Disease and Mineral and Bone Disorder Management
TABLE 14.3
Phosphorus-Binding Compounds
Content (Mineral/Metal/
Binder Source Rx Forms Element) Potential Advantages Potential Disadvantages
Aluminum hydroxide No Liquid, tablet, and capsule Aluminum content varies from Very effective phosphate-binding Potential for aluminum toxicity; altered bone
100 to >200 mg/tablet capacity; variety of forms mineralization, dementia; GI side effects
Calcium acetate Yes/No Capsule and tablet Contains 25% elemental Ca2+ Effective phosphate binding; Potential for hypercalcemia-associated risks,
(169 mg elemental Ca2+ per potential for enhanced including extraskeletal calcification and PTH
667 mg capsule) phosphate-binding capability suppression; more costly than CaCO3; GI side
over CaCO3; potentially less effects
calcium absorption
Calcium carbonate No Liquid, tablet, chewable, Contains 40% elemental Ca2+ Effective, inexpensive, and Potential for hypercalcemia-associated risks,
capsule, and gum (200 mg elemental Ca2+ per readily available including extraskeletal calcification and PTH
500 mg CaCO3) suppression; GI side effects
Calcium citrate No Tablet, liquid, and capsule Contains 22% elemental Ca2+ Not recommended in CKD Enhancement of aluminum absorption; GI side
effects
Calcium ketoglutarate Similar to other calcium salts; costly; GI side
effects; potentially less hypercalcemic than
calcium carbonate or acetate; not well studied
Calcium gluconate Tablet and powder Similar to other calcium salts; not well studied
Ferric citrate GI side effects; not well studied
Magnesium/calcium No Tablet ~28% elemental Mg2+ (85 mg) Effective; potential for lower GI side effects; potential for hypermagnesemia;
carbonate per total MgCO3 and 25% calcium load than pure not well studied
elemental Ca2+ (100 mg) per calcium-based binders
total CaCO3
Magnesium carbonate/ Yes Tablet Lack of availability worldwide; assumed to have
calcium acetate similar effects of its components
(Continued)
191
192
TABLE 14.3 (Continued)
Phosphorus-Binding Compounds
Content (Mineral/Metal/
Binder Source Rx Forms Element) Potential Advantages Potential Disadvantages
Sevelamer-HCl Yes Caplet None Effective; no calcium/metal; not Costly; potential for decreased bicarbonate
absorbed; potential for reduced levels; may require calcium supplement in
coronary/aortic calcification presence of hypocalcemia; GI side effects
compared with calcium-based
binders in some studies; reduces
plasma concentration of LDL-C
Sevelamer carbonate Yes Caplet and powder None Effective; no calcium/metal; not Costly; may require calcium supplement in
Abbreviations: CaCO3, calcium carbonate; CKD, chronic kidney disease; CKDMBD, chronic kidney diseasemineral and bone disease; GI, gastrointestinal; KDIGO, Kidney Disease:
Improving Global Outcomes; LDL-C, low-density lipoprotein cholesterol; PTH, parathyroid hormone; Rx, prescription.
Source: KDIGO, Kidney Int., 76 (suppl 113), S1S130, 2009. With permission.
Chronic Kidney Disease and Mineral and Bone Disorder Management 193
many tissues are subject to the actions of vitamin D. In addition to the parathyroid gland, vitamin
D receptors can be found in the myocytes, smooth muscle, endothelial cells of the CV system, in
the liver parenchyma cells, in the thymus, bone marrow, B cells, and T cells, as well as in the gas-
trointestinal, reproductive, exocrine, respiratory, musculoskeletal, renal, epidermis, central nervous
systems, hair follicles, fibroblasts, and stroma of connective tissues. The effect vitamin D deficiency
has on these organs and tissues remains a matter of intense research (Andress, 2006).
14.6 SUMMARY
CKDMBD is a debilitating preventable disease that has effects far beyond bone. Proper evaluation
and treatment starting in CKD Stage 3 is imperative to improving outcomes. Recent advances in
research have improved the understanding of the comorbidities of CKD, including CKDMBD, but
there is still much work to do. Table 14.1 contains a summary of suggested KDIGO and KDOQI
calcium and phosphorus target ranges. Table 14.2 shows initiation ranges for the treatment of the
elevated iPTH associated with CKDMBD. Table 14.3 shows phosphorus-binding compounds.
REFERENCES
Andress, D. 2005. Vitamin D treatment in chronic kidney disease. Semin Dial. 18:315321.
Andress, D. 2006. Vitamin D in chronic kidney disease: A systemic role for selection vitamin D receptor activa-
tion. Kidney Int. 69:3343.
Becker, B., Kronenberg, F., Kleistein, J., et al. 2005. Renal insulin resistance syndrome, adiponectin and car-
diovascular events in patients with kidney disease: The mild and moderate kidney disease study. J Am
Soc Nephrol. 16:10911098.
Block, G., Klassen, P., Lazarus, J., et al. 2004. Mineral metabolism, mortality, and morbidity in maintenance
hemodialysis. J Am Soc Nephrol. 15:22082218.
Brenner, B.M., ed. 2008. Brenner and Rectors the Kidney. 8thed. Philadelphia, PA: Saunders, 156213.
Brown, A. Dusso, A, Statopolsky, E.1999. Vitamin D. Am J Physiol. 277:F157F175.
Centers for Medicare & Medicaid Services (CMS), HHS. 2008. Medicare and Medicaid Programs; Conditions
for coverage for end stage renal disease facilities; Final rule. Available at: http://www.cms.gov/
CFCsAndCoPs/downloads/ESRDfinalrule0415.pdf (accessed July 17, 2011).
Cunningham, J. 2000. Are parathyroidectomies still appropriate in chronic dialysis patients? Semin Dial.
13:275278.
Dhingra, R., Sullivan, L., Fox, C., et al. 2007. Relations of serum phosphorus and calcium levels to the inci-
dence of cardiovascular disease in the community. Arch Intern Med. 167:879885.
Drueke, T., Moe, S., Langman, C. 2006. Treatment approaches in CKD. In: Olgaard K, ed. Clinical Guide to
Bone and Mineral Metabolism in CKD. New York: National Kidney Foundation, 119127.
Dusso, A., Brown, A., Slatopolsky, E. 2005. Vitamin D. Am J Physiol Renal Physiol. 289: F828.
Elder, G. 2002. Pathophysiology and recent advances in the management of renal osteodystrophy. J Bone
Miner Res. 17:20942105.
Foley, R., Parfry, P., Sarnak, M. 1998. Clinical epidemiology of cardiovascular disease in chronic renal disease.
Am J Kidney Dis. 32:S112S119.
Friis, Hahnemann, S., Weeke, E. 1968. Serum calcium and serum phosphorus in uraemia during administration
of sodium phytate and aluminum hydroxide. Acta Med Scand. 183:497505.
Ganesh, S., Stack, A., Levin, N., et al. 2001. Association of elevated serum PO4, CA x PO4 product, and
parathyroid hormone with cardiac mortality risk in chronic hemodialysis patients. J Am Soc Nephrol.
12:21312138.
Goodman, W. and Quarles, L. 2006. Mineral homeostasis and bone physiology. In Olgaard K, ed. Clinical
Guide to Bone and Mineral Metabolism in CKD. New York: National Kidney Foundation, 228.
Gutierrez, O., Isakova, T., Rhee, E., et al. 2005. Fibroblast growth factor-23 mitigates hyperphophatemia but
accentuates calcitriol deficiency in chronic kidney disease. J. Am. Soc. Nephrol. 16(7):22052215.
Hsu C.H. 2007. We have mismanaged calcium and phosphate in renal failure? Available at: http://www.uninet.
edu/cin2000/conferences/ChenHsu/ChenHsu.html
Kalantar-Zadeh, K., Kuwae, N., Regidor, D., et al. 2006. Survival predictability of time-varying indicators of
bone disease in maintenance hemodialysis patients. Kidney Int. 70:771780.
194 Nutrition Therapy for Chronic Kidney Disease
Kalantar-Zadeh, K., Shah, A., Duong, U., et al. 2010. Kidney bone disease and mortality in CKD: Revisiting
the role of vitamin D, calcimimetics, alkaline phosphatase, and minerals. Kidney Int. 78:S10S21.
Kasiske, B., Zeier, M., Chapman, J., et al. 2010. KDIGO clinical practice guideline for the care of kidney trans-
plant recipients: A summary. Kidney Int. 77(4):299311.
KDIGO. 2009. Clinical practice guideline for the diagnosis, evaluation, prevention, and treatment of chronic
kidney diseasemineral and bone disorder (CKDMBD). Kidney Int. 76 (suppl 113):S1S130.
K/DOQI. 2003. Clinical practice guideline for bone metabolism and disease in chronic kidney disease. Am J
Kidney Dis. (suppl 3).
Kestenbaum, B., Sampson, J., Rudser, K., et al. 2005. Serum phosphate levels and mortality risk among people
with chronic kidney disease. J Am Soc Nephrol. 16:520528.
Kim, H., Park, C., Shin, Y., et al. 2006. Calcitriol regresses cardiac hypertrophy and QT dispersion in secondary
hyperparathyroidism on hemodialysis. Nephron Clin Pract. 102:c21c29.
Kramer, H., Toto, R., Peshock, R., et al. 2005. Association between CKD and coronary artery calcification: The
Dallas Heart Study. J Am Soc Nephrol. 16:507513.
Levin, A., Bakris, G., Molitch, M., et al. 2007. Prevalence of abnormal serum vitamin D, PTH, calcium, and
phosphorus in patients with chronic kidney disease: Results of the study to evaluate early kidney disease.
Kidney Int. 71:3138.
Li, Y., Kong, J., Wei, M., et al. 2002. 1,25-dihydroxyvitamin D(3) is a negative endocrine regulator of the renin
angiotensin system. J Clin Invest. 110:229238
Mathieu, C. and Adornin, L. 2002. The coming of age of 1,25-dihydroxyvitamin D(3) analogs as immuno-
modulatory agents. Trends Mol Med. 8:174179.
Moe, S. 2001. Calcium and Phosphorus Balance in ESRD: Implications and Management. Cambridge, MA:
Genzyme Corporation.
Mitch, W. 2005. Beneficial responses to modified diets in treating patients with chronic kidney disease. Kidney
Int. 67:S133S135.
National Kidney Foundation (NKF). 2002. K/DOQI clinical practice guidelines for chronic kidney disease:
Evaluation, classification, and stratification. Am J Kidney Dis. 39(2 Suppl 1):S1266.
Nemeth, E., Heaton, W., Miller, M., et al. 2004. Pharmacodynamics of the type II calcimimetic compound
cincacalcet HCL. J Pharmacol Exp Ther. 308:627635.
Park, C., Oh, Y., Shin, Y., et al. 1999. Intravenous calcitriol regresses myocardial hypertrophy in hemodialysis
patients with secondary hyperparathyroidism. Am J Kidney Dis. 33:7381.
Popovtzer, M., Massry, S., Coburn, J., et al. 1969. The interrelationship between sodium, calcium, and magne-
sium, excretion in advanced renal failure. J Lab Clin Med. 73(5):763771. Available at: http://www.ncbi.
nlm.nih.gov/pubmed?term=Popovtzer%201969%20%20J%20Lab%20Clin%20Med
Potts, J., Jr. 2005. Diseases of the parathyroid gland and other hyper- and hypocalcemic disorders. In: Kasper,
D., Braunwald, E., Fauci, A., et al, eds. Harrisons Principles of Internal Medicine, 16th edition, New
York: McGraw Hill, 22492268.
Rodriguez, M., Caadillas, S., Lopez, I., et al. 2006. Regulation of parathyroid function in chronic renal failure.
J Bone Miner Metab. 24:164168.
Rodriguez, M., Nemeth, E., Martin, D. 2005. The calcium-sensing receptor: A key factor in the pathogenesis of
secondary hyperparathyroidism. Am J Physiol Renal Physiol. 288:F253F264.
Seiler, S., Heine, G., Fliser, D. 2009. Clinical relevance of FGF-23 in chronic kidney disease. Kidney Int.
76:S34S42.
Silver, J. and Levi, R. 2005. Regulation of PTH synthesis and secretion relevant to the management of second-
ary hyperparathyroidism in chronic kidney disease. Kidney Int. 67 (suppl 95):S8S12.
Skorecki, K., Green, J., Brenner, B. 2005. Chronic renal failure. In: Kasper, D., Braunwald, E., Fauci, A. eds.
Harrisons Principles of Internal Medicine, 16th edition, New York: McGraw Hill, 16531663.
Slatopolsky, E., Weerts, C., Thielan, J., et al. 1984. Marked suppression of secondary hyperparathyroid-
ism by intravenous administration of 1,25-dihydroxy-cholecalciferol in uremic patients. J Clin Invest.
74:21362143.
Timms, P., Mannan, N., Hitman, G., et al. 2002. Circulating MMP9, vitamin D and variation in the TIMP-1
response with VDR genotype: Mechanisms for inflammatory damage in chronic disorders? QJM.
95:787796.
Tokumoto, M., Tsuruya, K., Fukuda, K., et al. 2002. Reduced p21, p27 and vitamin D receptor in the nodular
hyperplasia in patients with advanced secondary hyperparathyroidism. Kidney Int. 62:11961207.
Tonelli, M., Sacks, F., Pfeffer, M., et al. 2005. For cholesterol and recurrent events (CARE). Circulation
112:26272633.
Chronic Kidney Disease and Mineral and Bone Disorder Management 195
Uhlig, K., Berns, J., Kesterbaum, B., et al. 2010. KDOQI U.S. commentary on the 2009 KDIGO clinical
practice guideline for the diagnosis, evaluation, and treatment of CKD-mineral and bone disorder (CKD
MBD). Am J Kidney Dis. 55:773799.
U.S. Department of Agriculture, Agricultural Research Service. 2001. USDA Nutrient Database for Standard
Reference, Release 14. Nutrient Data Laboratory.
Zisman, A., Hristova, M., Ho, L., et al. 2007. Impact of ergocalciferol treatment of vitamin D deficiency on
serum parathyroid hormone concentrations in chronic kidney disease. Am J Nephrol. 27:3643.
15 Diabetes Management
Fran Kittell
University of WisconsinMadison
CONTENTS
15.1 Introduction......................................................................................................................... 197
15.2 Definitions........................................................................................................................... 197
15.3 Glycemic Control................................................................................................................ 199
15.4 Hypertension....................................................................................................................... 201
15.5 CVD and DKD....................................................................................................................202
15.6 Diabetic Gastropathy........................................................................................................... 203
15.7 Dietary Carbohydrate.......................................................................................................... 203
15.8 Dietary Protein....................................................................................................................204
15.9 Dietary Fat...........................................................................................................................205
15.10 Vitamins and Minerals........................................................................................................206
15.11 Obesity and DKD................................................................................................................206
15.12 Renal Replacement Therapy...............................................................................................206
15.13 Synopsis...............................................................................................................................207
15.14 Conclusion...........................................................................................................................208
References.......................................................................................................................................208
15.1 INTRODUCTION
Diabetes is the leading cause of kidney disease in the United States. According to the Centers for
Disease Control, in 2008 nearly 8% of the population in the United States had diabetes (National
Diabetes Fact Sheet, 2008; USRDS, 2009). Diabetes incidence is increasing worldwide, and it has
been predicted that this incidence will double by the year 2030 (Wild et al., 2004). The Diabetes
and Chronic Kidney Disease Work Group of the National Kidney Foundation Kidney Disease
Outcomes Quality Initiative (KDOQI) states that the burden of diabetic kidney disease (DKD)
is appearing in Africa, India, Asia, and the Pacific Islands replacing infectious disease, which
was previously thought to be the greatest threat (NKF, 2007). World Kidney Day 2010, under the
auspices of the International Society of Nephrology and the International Federation of Kidney
Foundations and with the International Diabetes Federation, has now established a day recogniz-
ing the need to alert governments, health providers, doctors, and patients of the increasing health
and socioeconomic problems related to DKD (Atkins and Zimmet, 2010).
15.2 DEFINITIONS
Diabetes is a group of diseases identified by elevated serum glucose levels resulting from defects
in insulin production, insulin action, or both. Most cases of diabetes in the United States are type
2, previously called noninsulin-dependent diabetes mellitus or adult-onset diabetes (National
Diabetes Fact Sheet, 2008; NKF, 2007). Those with type 2 diabetes can progress to dependence
on insulin as beta cell function decreases and as insulin resistance increases. Approximately
5%10% of diabetes in the United States is type 1, previously called insulin-dependent diabetes
197
198 Nutrition Therapy for Chronic Kidney Disease
mellitus or juvenile-onset diabetes (National Diabetes Fact Sheet, 2008). People with type 1
diabetes are dependent on exogenous insulin for day-to-day survival (NKF, 2007). Pre-diabetes
is another condition in which a persons blood sugar is abnormally elevated but not enough for
a diagnosis of type 2 diabetes. Without lifestyle interventions, people with pre-diabetes will
develop type 2 diabetes within 10 years. Other names for pre-diabetes include impaired glucose
tolerance or impaired fasting glucose (National Diabetes Fact Sheet, 2008).
In the recent past, individuals diagnosed with type 1 diabetes would inevitably suffer from kid-
ney disease, that is, if they were able to survive the associated diabetes complication of cardiovascu-
lar disease (CVD). Type 2 diabetes, on the other hand, was considered less severe (benign) and not
associated with the consequences of kidney disease. Today, there is sufficient evidence to indicate
that the risk of nephropathy with progression to end-stage kidney disease is similar between the two
types of diabetes (Hasslacher et al., 1989; NKF, 2007; Ritz and Orth, 1999).
There are a number of possible reasons for the dramatic increase in the number of patients with
type 2 diabetes with end-stage kidney disease. The K/DOQI Diabetes and Chronic Kidney Disease
Work Group attributes it to the growing worldwide obesity problem and the subsequent diagnosis of
type 2 diabetes. Other etiologies may be the accepted use of angiotensin-converting (ACE) inhibi-
tors, angiotensin blockers (ARBs), and statins, which have improved the treatment of hypertension
(HTN) and coronary heart disease, enabling more people with type 2 diabetes to live long enough
for nephropathy and end-stage kidney disease to develop. Regardless, kidney damage will ensue in
either type 1 or type 2 diabetes (NKF, 2007; USRDS, 2009).
DKD, formerly known as diabetic nephropathy, is kidney disease specific to diabetes.
Microalbuminuria, defined as albumincreatinine ratio (ACR) of 30299 mg/24 h, is the harbin-
ger of the diagnosis of DKD. With the development of more sensitive assays specific for albumin,
smaller changes in albuminuria can be detected. The course of DKD can be defined by these pro-
gressive incremental losses of urinary albumin expressed in ranges, from the initial appearance
of microalbuminuria onto macroalbuminuria, defined as ACR > 300 mg in 24 h, followed by the
eventual increase in serum creatinine leading to overt DKD.
One pathological pathway describing elevated plasma glucose levels leading to nephropathy is
the advanced glycation end product pathway. This pathway is capable of producing tissue changes
that can occur in the glomeruli (EDIC, 2003). Other possible pathological changes explaining DKD
include increased glomerular basement membrane thickness, microaneurysm formation, and mesan-
gial nodule formation, or Kimmelsteil-Wilson bodies (Fowler, 2008). Urinary protein losses can
be correlated to the estimated glomerular filtration rate (eGFR). The K/DOQI Clinical Practice
Guidelines for Diabetes delineate steps for diagnosing DKD; these can be found in Table15.1 (NKF,
2007).
TABLE 15.1
DKD According to Staging by GFR and Level of Albuminuria
Albuminuria
GFR (mL/min) CKD Stage Normoalbuminuria Microalbuminuria Macroalbuminuria
>60 1+2 At risk Possible DKD DKD
3060 3 Unlikely DKD Possible DKD DKD
<30 4+5 Unlikely DKD Unlikely DKD DKD
Source: National Kidney Foundation, Am. J. Kidney Dis. 49, S22S23, 2007.
Abbreviations: CKD, chronic kidney disease; DKD, diabetic kidney disease; GFR, glomerular filtration rate.
Diabetes Management 199
monitoring of glucose levels is essential to avoid hypoglycemia with subsequent dose reductions
of oral medications and insulin likely. In fact, more specifically, when GFR is <50 mL/min, the
insulin dose should be reduced by 25%, and by 50% if GFR is <10 mL/min (Aronoff et al., 1983;
Bennett et al., 1994). Lastly, individualization, including possibly liberalization, of glycemic
goals needs to be evaluated.
Hemoglobin A1c is the gold standard for assessing and monitoring long-term glycemic control in
those with diabetes. Percentages of A1c values correlate to average blood glucose over the preceding
6090 days. In the general population, a strong relationship exists between A1c and mean plasma
glucose levels. For every percentage increase in A1c, there is approximately a 35 mg/dL change in
mean plasma glucose (Williams, 2010). The K/DOQI Diabetes and CKD work group defers to the
American Diabetes Association (ADA) Guidelines for the recommended frequency in measuring
A1c twice annually for stable people with diabetes and four times a year in those who are not reach-
ing their glycemic goals or whose therapy has changed (ADA, 2010b; NKF, 2007). Unfortunately,
progressive kidney disease can falsely lower the A1c measurement. Low levels of A1c can be attrib-
uted to reduced red blood cell mass, reduced red blood cell lifespan, hemolysis, iron deficiency, and
hemodilution caused by blood transfusions. On the other hand, a number of variables can falsely
elevate levels of A1c, and they include carbamylated hemoglobin interfering with the assay, uremic
acidosis, hypertriglyceridemia, hyperbilirubinemia, and alcohol addiction (Joy et al., 2002; NKF,
2007). Initial data regarding glycated albumin as a more sensitive indicator of glycemic control for
those with DKD appears promising, but their validity has yet to be determined (Inaba et al., 2007;
TABLE 15.2
Comparison of A1c and Estimated
Average Glucose (eAG)
A1c (%) eAG (mg/dL)
5 97
5.5 111
6 126
6.5 140
7 154
7.5 169
8 183
8.5 197
9 212
9.5 226
10 240
10.5 255
11 269
11.5 283
12 298
Williams, 2009). Despite A1cs limitations, those with DKD are, still, encouraged to strive for an
as close to normal (<6%) as possible goal of reaching glycemic levels in the nondiabetic range
without significant hypoglycemia to prevent or slow the progression of retinopathy, neuropathy, and
possibly macrovascular disease. Once the patient is on dialysis, survival improves with better gly-
cemic control (Nathan et al., 2006; NKF, 2007). It is becoming more apparent that low A1c values
may actually be associated with higher mortality rates in patients with diabetes on chronic hemo-
dialysis (HD) (Morioka et al., 2001; Williams, 2009). In fact, extreme high or extreme low A1c is
being found to decrease survivability for those with diabetes on dialysis (Joachim, 2010; Williams,
2009; Williams et al., 2010). Recognizing these variables that ultimately affect and make consistent
glucose control more difficult as DKD progresses is essential. Consequently, individualizing A1c
targets using clinical judgment is essential. Standardized A1c levels are available and can assist the
professional in determining estimated average glucose (eAG). The formula describing the relation-
ship between A1c and eAG is: (28.7 A1c) 46.7 = eAG (ADA, 2010b; Nathan et al., 2008). See
Table 15.2 for comparison chart between A1c and eAG.
15.4 HYPERTENSION
HTN is the second leading cause of kidney disease in the United States (USRDS, 2009). Most
of those with DKD have HTN. K/DOQI recommends the target blood pressure for those with
DKD, stages 14 to be <130/80 mm Hg based upon the Joint National Committee on Prevention,
Detection, Evaluation, and Treatment of High Blood Pressure, JNC 7 (Chobanian et al., 2003;
Inaba et al., 2007; NKF, 2004, 2007). For those with proteinuria, >1 g protein, target blood pres-
sure is <120/80 mm Hg. The first-line treatment for achieving this goal includes ACE inhibitors
or ARBs often in combination with a diuretic. The kidney-protective effects of ACE inhibitors
and ARBs include decreasing urinary albumin excretion, slowing the increase in albumin excre-
tion, and delaying the progression from microalbuminuria to macroalbuminuria (Chobanian et al.,
2003; NKF, 2004, 2007). A possible explanation for their kidney-protective effects can be their
capability of decreasing efferent arteriolar resistance in the kidney thereby decreasing intraglo-
merular pressure in the kidney. In addition, these agents may affect the permselective character-
istics of the glomeruli, which may explain their antiproteinuric qualities (Fowler, 2008; Morelli
et al., 1990). Care must be taken for potential hyperkalemia, a side effect of ACE inhibitors and
ARBs; although this could be canceled out with the potassium-wasting diuretic. Regardless, even
though limiting dietary potassium is typically not necessary until urine output dips to 1000 mL/
day, it may be prudent to educate patients with DKD about high potassium-containing foods such
as chocolate, nuts, dried fruit, citrus fruit/citrus fruit juice, potatoes, and potassium-containing
salt substitutes that they should limit as a precaution. Since most people with DKD have HTN
associated with sodium retention, limiting dietary sodium intake to 2.3 g/day is recommended
based on the Dietary Approaches to Stop Hypertension (DASH) and the DASH-sodium diets, with
modifications for possible potassium and phosphorus limitations. Modifications include a 0.81.0
g/day phosphorus limitation and a 24 g/day potassium limitation. The DASH diet encourages
consumption of fruit, vegetables, and low-fat dairy products, along with whole grains, poultry, fish,
and nuts. Only small amounts of red meat, sweets, and sugar-containing beverages are encouraged.
The diet also has decreased amounts of total and saturated fat and cholesterol and a slight increase
in protein. The DASH diet includes 810 servings of fruit and/or vegetables and 23 servings
low-fat dairy products daily. It leads to an average 11.6/3.5 mm Hg blood pressure reduction. The
DASH-Sodium diet recommends a sodium limitation of 15002400 mg daily, which can achieve
an additional 3.5/2.2 mm Hg blood pressure reduction. This is equal to or greater than what could
be achieved with single-drug therapy (Sacks et al., 2001; Wisconsin Diabetes Advisory Group,
2008). A summary of the DASH diet with modifications can be found in Table 15.3 (NKF, 2004).
Without lifestyle changes, such as limiting dietary salt, the effects of ACE inhibitors and ARBs
will be blunted (NKF, 2007).
202 Nutrition Therapy for Chronic Kidney Disease
TABLE 15.3
Macronutrient Composition and Mineral Content of the Dietary
Approaches to Stop Hypertension (DASH) Diet Recommended by
JNC 7, with Modifications for Stages 34 of CKD
Stage of CKD
Nutrient Stages 14
Sodium (g/day) <2.4
Total fat (% of calories) <30
Saturated fat (% of calories) <10
Cholesterol (mg/day) <200
Carbohydrate (% of calories) 5060
Stages 12 Stages 34
Protein (g/kg/day, % of 1.4 (~18) 0.60.8 (~10)
calories)
Phosphorus (g/day) 1.7 0.81.0
Potassium (g/day) >4 24
Abbreviations: CKD, chronic kidney disease; JNC, Joint National Committee on Prevention,
Detection, Evaluation, and Treatment of High Blood Pressure.
Source: National Kidney Foundation, K/DOQITM Clinical Practice Guidelines on
Hypertension and Antihypertensive Agents in Chronic Kidney Disease, 2004.
TABLE 15.4
Diabetic Gastropathy Dietary Recommendations
Mealtime Strategies Foods to Avoid with Bezoars
Chew well Oranges Green beans
Small meals Apples Coconut
Frequent meals Berries Figs
Low-fat Persimmons Brussel sprouts
Low in insoluble fiber Sauerkraut Dried beans and peas
Sit up 1 h after eating/walk after eating Potato skins
TABLE 15.5
Kidney Friendly 15 g Glucose Sources
10 jelly beans
8 lifesavers
2 restaurant packets of regular jelly
1 tube frosting
1 tube glucose gel
3 glucose tablets
of the food. This does not mean high-sugar foods are to be encouraged. In fact, as with those with-
out diabetes, discouraging foods containing high amounts of sugar is recommended as they are
energy NOT nutrient dense. Prioritizing nutrition messages, including liberalizing CHOs, may be
necessary to facilitate compliance. Recommended CHO food sources include whole grains, fruits,
vegetables, and nonfat dairy products, with modifications for potassium and phosphorus, which can
include but are not limited to whole grain white bread; oat-, wheat-, or corn-based cereals; brown
rice; apples with skins, pears, grapes; green beans, carrots, green peppers, broccoli, corn, green
peas, and chick peabased humus.
Adequate fiber intake is also encouraged for a number of reasons: (1) it assists in glycemic control
by slowing CHO absorption; (2) its cholesterol lowering effect has possible cardiovascular benefits;
and (3) it helps to prevent constipation, particularly for those on peritoneal dialysis, to assist in
adequate clearances. One study demonstrated the positive effects of 50 g fiber consumed daily in
type 2 diabetes in lowering postprandial hyperglycemia, decreasing hyperinsulinemia, and reduc-
ing both cholesterolemia and triglyceridemia (Chandalia et al., 2000).
Because of the potential for widely fluctuating blood sugars, self-monitoring of blood glucose
(SMBG) is encouraged three or more times daily, before meals and at bedtime. In the case of hypo-
glycemia (less than 70 mg/dL plasma glucose), a kidney-friendly 15 g CHO source, preferably pure
glucose, is recommended. Fruit and fruit juice are less preferred because they contain fructose and
galactose, which must be converted to glucose in the liver before they can effectively raise blood
glucose levels (Diabetes Mellitus, 2007; McDougall et al., 2001). A list of kidney-friendly 15-g glu-
cose sources can be found in Table 15.5. Be aware of the metabolic repercussions of hyperglycemia,
such as hyperkalemia, due to cell shifts and possibly increased thirst and subsequent fluid overload,
particularly with lack of polyuria.
mesangial stretch, solute load, toxins, and overall nephron activity, eventually sclerosing the kid-
neys (Brenner et al., 1982; Wolk et al., 2007). More specifically, in persons with both diabetes and
HTN, a higher protein intake leads to an increase in microalbuminuria (Wrone et al., 2003).
The debate continues over the level of protein restriction that is most effective in decreasing symp-
toms of uremia, such as nausea and vomiting, while slowing the progression of kidney disease with-
out prompting malnutrition. The Modified Diet in Renal Disease Study looked at this very question
with mixed results, although it excluded participants with diabetes. Evidence is limited and often not
significant, yet a few studies have suggested that limiting dietary protein intake in those with type 1
diabetes slowed the progression of pathological changes in the DKD kidney. One meta-analysis in
particular found that decreasing protein intake to 0.73 0.15 g protein/kg had a greater affect on the
rate of GFR decline in diabetic patients than in nondiabetic patients. Fewer studies of type 2 diabetes
and dietary protein intake relative to kidney progression are available (Hansen et al., 2002; Kasiske et
al., 1998; Pedrini et al., 1996; Walker et al., 1989; Zeller et al., 1991) Even so, the KDOQI Diabetes
and CKD Guidelines and the ADA recommend a dietary protein intake for people with diabetes and
CKD stages 14 of 0.8 g/kg/day (Chandalia et al., 2000; NKF, 2007). For CKD stage 5D, the recom-
mended dietary protein intake is no different for one with DKD than for the nondiabetic, 1.2 g pro-
tein/kg/day and 1.21.3 g protein/kg/day for those on HD and PD, respectively (NKF, 2000; 2007).
People in the United States tend to eat too much protein, consuming approximately 1.04 g protein/
kg/day (Wright et al., 2003). To educate a person with DKD to limit protein intake, especially in the
face of manipulating several other dietary variables, may prove too daunting. And, apparently, not
all protein is created equal. It has been found vegetarians have lower GFRs than omnivores (Margett
etal., 1986; Wiseman et al., 1987). The type of protein consumed partially mediates renal hemo-
dynamics. The largest change in postprandial renal hemodynamics appears to be induced by beef,
followed by poultry, fish, and plant proteins. Small studies have uncovered promising new evidence
regarding the intake of vegetable protein, more specifically, soy protein, regardless of the quantity, as
being renal protective by lowering GFR, renal plasma flow, and microalbuminemia in humans com-
pared with the ingestion of animal protein in those with early microalbuminemia or more established
macroalbuminemia (Azadbakht and Esmaillzadeh, 2009; Bosch et al., 1986; de Mello et al., 2006;
Jibani et al., 2009; Kontessis et al., 1990; Williams et al., 1987). Soybeans contain high concentra-
tions of isoflavones, genistein, and daidzein, which exert estrogen-like effects. The modified DASH
diet provides a greater portion of these isoflavones with its emphasis on vegetables, nuts, legumes,
fish, and poultry (and little red meat). Whether isoflavones can block the inflammatory responses
seen in the progression of kidney disease is still to be seen. In the meantime, recommending a com-
promise alternating between conventionally low protein and a greater proportion of vegetable protein
may help in making the diet more palatable and result in greater compliance (Almeida et al., 2008;
Anderson etal., 1998; de Mello et al., 2006; Gross et al., 2002; NKF, 2007; Sacks et al., 2001).
ultimately and effectively decreasing clearance of LDL-C. Dietary recommendations for manag-
ing hypertriglyceridemia include weight loss (if necessary) along with limiting intake of CHO,
sugar, and alcohol (Haffner, 1998; Sheard and Clark, 2000; Steiner, 1999). Dietary suggestions can
include reduced consumption of regular soda, fruit juice, desserts, and other sweetened confections.
Alcohol should be limited to one drink per day or less for women and two drinks per day or less
for men (ADA, 2008). A fasting lipid panel is recommended annually to monitor cholesterol and
triglycerides for those with DKD (ADA, 2008; NKF, 2007; Wisconsin Diabetes Advisory Group,
2008). More recently, it has been found that replacing up to 40% of the calories from CHO with
monounsaturated fat, such as olive oil or canola oil, decreases triglyceride levels (ADA, 2004; Garg
et al., 1994, 1988; Kris-Etherton, 1999).
The weight gain that is a common side effect of peritoneal dialysis is another factor to consider if
the patient is already overweight. On the other hand, hypoglycemic events are greater within 24 h
of HD, as noted previously (Mak, 1991).
15.13 SYNOPSIS
The complexity of the recommended diet for DKD warrants the involvement of an experienced
dietitian. Medical nutrition therapy is an integral component of early diabetes education (Brand-
Miller et al., 2003). Once DKD develops, it is recommended that an experienced dietitian who
is knowledgeable about both CKD and diabetes participate in the individuals dietary education,
pre-dialysis and/or on dialysis. Frequent interaction with a dietitian fostering self-management can
improve and achieve dietary intake goals and clinical outcomes (ADA, 2008; NKF, 2007). The
recommended diet for DKD should be no different from the diet recommended for nondiabetic
CKD. Neither should be partaking in sugary sweets such as, cakes, pies, cookies, candies, and
regular soda pop, containing little to no nutritional value. Because the total amount of CHO eaten
has been found to be more important than type or source of CHO, the recommended CHO should
be no different between nondiabetic and diabetic patients. Liberalizing and encouraging high-fiber
CHOs that are relatively lower in phosphorus and potassium-containing fruit and vegetables such as
broccoli, corn, green beans, green and red peppers, cucumbers, apples, grapes, berries, pineapple
along with whole grain white bread, oat-based cereals and breads, tortillas, popcorn, and pretzels is,
again, no different for those with or without diabetes, especially if fluid and protein are restricted,
for any modest cardiovascular benefits and for constipation prevention. Limiting protein intake to
0.8 g protein/kg/day for CKD stages 14 is recommended just as with nondiabetes. This limitation
is more important in individuals with type 2 diabetes because ingested protein has been found to
increase serum insulin levels and not serum glucose levels, consequently, protein-containing foods
exclusive of complex CHOs are not encouraged to prevent hypoglycemia (ADA, 2008; Gannon and
Nuttall, 2001). Of the allowed protein, more fish, poultry (preferably fresh with lower phosphorus
content) and plant proteins, particularly soy protein, is encouraged.
A reduction of sodium intake down to 1500 mg is being advocated for all those with HTN,
which the U.S. Dietary Guidelines indicate is prevalent by 70% (USDA and USDHHS, 2010). The
DASH-sodium diet, as previously mentioned, advocates a 15002400 mg sodium limitation, by
avoiding packaged, prepared, processed foods. Encourage cooking from scratch, time permitting.
A summary of all dietary nutrient recommendations for one with DKD can be found in Table15.6.
Obtaining a dietary recall of typical dietary intake can help reveal any potential barriers that may
need to be addressed. Having the patient attempt to identify these barriers may help empower the
patient toward self-management. Encourage needed changes by providing information and offering
support. Guide the patient to prioritize suggested recommendations, beginning with vigilance in
checking blood sugar, SMBG, at least four times daily, especially given the fluctuating blood sugar
levels typically seen in DKD. Insulin doses frequently decrease, and SMBG can prevent hypoglyce-
mia. Often, patients stop testing once they are on dialysis. The random blood glucose testing done
at the dialysis treatment center cannot substitute for recommended frequent home testing.
Inform patients to expect shifts in serum levels, such as with serum potassium, and reassure them
that they are not to blame. These spikes or nadirs are common in CKD and likely not due to food
eaten, but potentially a number of variables, including decreased renal clearance or to medications
being prescribed. An example includes ACE inhibitors and not dietary intake causing hyperkale-
mia. Inform the person that his or her insulin dose will more than likely decrease. Prioritize dietary
suggestions as dictated by the constantly changing serum potassium and phosphorus values often
seen. Educate the person about anticipated need for and timing of phosphorus binder medication.
Make it clear that it is not punishment when binder medications are prescribed; they are needed
because the kidneys are unable to clear phosphorus adequately. Focus on including cited preferred
foods into dietary patterns.
208 Nutrition Therapy for Chronic Kidney Disease
TABLE 15.6
Recommended Nutrient Intake for DKD, Stages 14
Nutrient Recommendation
Protein (g/kg/day) 0.81.0 emphasizing more poultry, fish, plant protein (soy), less red meat;
discourage high protein
Total fat (% of calories) <30%
Saturated fat (% of calories) < 7%
Monounsaturated fat (% of calories) Up to 40%, such as olive oil or canola oil
Trans fat Minimal
Cholesterol (mg/day) <200
Carbohydrate Discourage sweets, regular soda, sweetened confections
Total fiber (g/day) 3050 through fresh fruit/vegetables and whole grains
Sodium (g/day) 1.52.4
Potassium (g/day) Unrestricted until serum levels increase, then 24; monitor with ACE-Inhibitor
use
Phosphorus (mg/day) 8001000
Calcium (mg/day) <2, total between medications and oral intake
Vitamins <2.5 mg folic acid; <25 mg vitamin B6; <1 mg vitamin B12
Assure patients with DKD that splurging is fine; in fact, work splurges into their recommended
food pattern. The dietitian can work favorite foods into the individuals daily food patterns, allow-
ing continued enjoyment. For example, chocolate, if necessary, can be consumed with a phosphorus
binder medication and with a meal for decreased phosphorus and glucose absorption with a mixed-
fuel meal. The dietitian need not be thought of as the food police but as an assistant. Remember
that diet may be the last means of control for the person. Frequent interactions integrating lifestyle
modifications through a series of small changes with the patient, more easily enforced particularly
if in-center HD, can improve compliance, creating positive reinforcement.
15.14 CONCLUSION
Diabetes is a progressive disease, and DKD is a phase of the progression. Early on, such as in pre-
diabetes, weight loss, if needed, can delay the onset of type 2 diabetes. Continued weight manage-
ment along with tight glycemic control is suggested to delay microalbuminuria, or early DKD. In
more established DKD, macroalbuminuria, a less stringent (due to the difficulty in avoiding hypo-
glycemia) but careful glycemic control is advocated to delay the need for renal replacement therapy.
SMBG is highly encouraged three or more times daily. Diet therapy is pivotal every step of the way
of this progression as it is less expensive, associated with fewer risks and side effects and promotes
a healthy lifestyle. Optimal diet therapy includes adequate provision of calories to achieve or main-
tain an ideal BMI, maintain a positive nitrogen balance, achieve optimal lipid levels, and individual-
ize A1c levels to prevent complications while optimizing the patients overall health and well-being.
REFERENCES
Abrahamsson, H. 2007. Treatment options for patients with severe gastroparesis. Gut 56: 877883.
Action to Control Cardiovascular Risk in Diabetes Study Group (ACCORD). 2008. Effects of intensive glucose
lowering in type 2 diabetes. N Engl J Med. 358: 25452559.
Advance Collaborative Group. 2008. Intensive blood pressure control and vascular outcomes in patients with
type 2 diabetes. N Engl J Med 358: 25602572.
Diabetes Management 209
Alibibi, R. and McCallum, R.W. 1983. Metoclopramide: Pharmacology and clinical application. Ann Intern
Med 98: 8695.
Almeida, J., Zelmanovitz, T., Vaz, J., et al. 2008. Sources of protein and polyunsaturated fatty acids of the diet
and microalbuminemia in type 2 diabetes mellitus. J Am Coll Nutr 27: 528537.
American Diabetes Association (ADA). 2004. Dyslipidemia management in adults with diabetes. Diabetes
Care 27: S68S71.
American Diabetes Association (ADA). 2008. Nutrition recommendations and interventions for diabetes.
Diabetes Care 31: S61S78.
American Diabetes Association (ADA). 2010a. Living with diabetes: Estimated average glucose (eAG). http://
www.diabetes.org (accessed September 10, 2010).
American Diabetes Association (ADA). 2010b. Standards of medical care in diabetes-2010. Diabetes Care 33:
S11S61.
Anderson, J., Blake, J, Turner, J., et al. 1998. Effects of soy protein on renal function and proteinuria in patients
with type 2 diabetes. Am J Clin Nutr 68: 1347S1353S.
Aronoff, G., Morrison, G., Golper, T., et al. 1983. Drug prescribing in renal failure. Am J Kidney Dis 3: 155193.
Atkins, R. and Zimmet, P. 2010. Diabetic kidney disease: Act now or pay later. J Nephrol 23: 14.
Azadbakht, L. and Esmaillzadeh, A. 2009. Soy-protein consumption and kidney-related biomarkers among
type 2 diabetics: A crossover, randomized clinical trial. J Renal Nutr 19: 479486.
Beard, P. 2002. Methods for treating diabetic gastroparesis. J Infus Nurs 25: 105108.
Bennett, W., Aronoff, G.R., Golper, T., et al. 1994. Dosing Guidelines for Adults. Philadelphia: American
College of Physicians.
Blair, D. 2009. Nutrition therapy for gastroparesis. Renal and Urology News. h ttp://www.renalandurologynews.
com/nutrition-therapy-for-gastroparesis/article/135966/ (accessed October 11, 2010).
Bosch, J., Lew, S., Glabman, S., et al. 1986. Renal hemodynamic changes in humans: Response to protein load-
ing in normal and disease kidneys. Am J Med 81: 809815.
Brand-Miller, J., Petocz, P., Hayne, S., et al. 2003. Low glycemic index diets in the management of diabetes.
Diabetes Care 26: 22612267.
Brenner, B., Meyer, T., Hostetter, T. 1982. Dietary protein intake and the progressive nature of kidney disease.
N Engl J Med 307: 652660.
Chandalia, M., Gar, A., Lutjohann, D., et al. 2000. Beneficial effects of high dietary fiber intake in patients with
type 2 diabetes mellitus. N Engl J Med 342: 13921398.
Chobanian, A., Bakris, G., Black, H., et al. 2003. Seventh report of the joint national committee on prevention,
detection, evaluation, treatment of high blood pressure. Hypertension 42: 12061252.
Cusi, K., Maezono, K., Osman, A., et al. 2000. Insulin resistance differentially affects the PI 3-kinase and MAP
kinase-mediated signaling in human muscle. J Clin Invest 105: 311320.
Delahanty, L. 1998. Implications of the diabetes control and complications trial for renal outcomes and medical
nutrition therapy. J Renal Nutr 8: 5963.
de Mello, V., Zelmanovitz, T., Perassolo, M., et al. 2006. Withdrawal of red meat from the usual diet reduces
albuminuria and improves serum fatty acid profile in type 2 diabetes patients with macroalbuminuria. Am
J Clin Nutr 83: 10321038.
Diabetes Control and Complications Trial Research Group. 1993. The effect of intensive treatment of diabetes
on the development and progression of long-term complications in insulin-dependent diabetes mellitus.
N Engl J Med 329: 977986.
Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/
EDIC) Study Research Group. 2005. Intensive diabetes treatment and cardiovascular disease in patients
with type I diabetes. N Engl J Med 353: 26432653.
Diabetes Prevention Program Research Group (DCCT). 2002. Reduction in the incidence of type 2 diabetes
with lifestyle intervention or metformin. N Engl J Med 346: 393403.
Dluhy, R. and McMahon, G. 2008. Intensive glycemic control in the ACCORD and ADVANCE trials. N Engl
J Med 358: 26302633.
Duckworth, W., Abraira, C., Moritz, T., et al. 2009. Glucose control and vascular complications in veterans with
type 2 diabetes. N Engl J Med 360: 129139.
Eknoyan, G. 2007. Obesity, diabetes, and chronic kidney disease. Curr Diab Rep 7: 449453.
Epidemiology of Diabetes Interventions and Complications (EDIC) Study. 2003. Sustained effect of intensive
treatment of type I diabetes mellitus on development and progression of diabetic nephropathy. JAMA
290: 21592167.
Fowler, M. 2008. Microvascular and macrovascular complications of diabetes. Clinical Diab 26: 7782.
Freeman, J., Cobden, I., Heaton, A., et al. 1985. Gastric emptying in chronic renal failure. Br Med J 291: 1048.
210 Nutrition Therapy for Chronic Kidney Disease
Gannon, M. and Nuttall, F. 2001. Effect of a high protein, low carbohydrate diet on blood glucose control in
people with type 2 diabetes. J Clin Endocrinol Metab 86: 10401047.
Garg, A., Bantle, J., Henry, R., et al. 1994. Effects of varying carbohydrate content of diet in patients with non-
insulin-dependent diabetes mellitus. JAMA 271: 14211428.
Garg, A., Bonanome, A., Grundy, S., et al. 1988. Comparison of a high-carbohydrate diet with a high-monoun-
saturated-fat diet in patients with non-insulin-dependent diabetes mellitus. N Engl J Med 319: 829834.
Gerich, J., Meyer, C., Woerle, H. 2001. Renal gluconeogenesis. Diabetes Care 24: 382391.
Gross, J., Zelmanovitz, T., Moulin, C., et al. 2002. Effect of a chicken-based diet on renal function and lipid
profile in patients with type 2 diabetes: A randomized crossover trial. Diabetes Care 25: 645651.
Haffner, S. 1998. Management of dislipidemia in adults with diabetes. Diabetes Care 21: 160178.
Hajjar, S., Fadda, G., Thanakitcharu, P., et al. 1992. Reduced activity of Na+-K+ ATPase of pancreatic islets in
chronic renal failure: Role of secondary hyperparathyroidism. J Am Soc Nephrol 2: 13551359.
Hansen, H., Tauber-Lassen, E., Jensen, B., et al. 2002. Effect of dietary protein restriction on prognosis in
patients with diabetic nephropathy. Kidney Int 62: 220228.
Hasslacher, C., Ritz, E., Wahl, P., et al. 1989. Similar risks of nephropathy in patients with type I or type II
diabetes mellitus. Nephrol Dial Transplant 4: 859863.
Haviv, Y., Sharkia, M., Safadi, R. 2000. Hypoglycemia in patients with renal failure. Renal Fail 22: 219222.
Hebbard, G., Wei, M., Dent, J., et al. 1996. Hyperglycaemia effects proximal gastric motor and sensory func-
tion in normal subjects. Eur J Gastroenterol Hepatol 8: 211217.
Holman, R., Paul, S., Bethel, M., et al. 2008. Ten year follow-up of intensive glucose control in type 2 diabetes.
N Engl J Med 359: 15771589.
House, A., Eliasziw, M., Cattran, D., et al. 2010. Effect of B-vitamin therapy on progression of diabetic
nephropathy. JAMA 303: 16031609.
Inaba, M., Okuno, S., Kumeda, Y., et al. 2007. Glycated albumin is a better glycemic indicator than glycated
hemoglobin values in hemodialysis patients with diabetes: Effects of anemia and erythropoietin injec-
tion. J Am Soc Nephrol 18: 896903.
Jibani, M., Bloodworth, L., Foden, E., et al. 2009. Predominantly vegetarian diet in patients with incipient and
early clinical diabetic nephropathy: Effects on albumin excretion rate and nutritional status. Diabet Med
8: 949953.
Joachim, H. 2010. Hemoglobin A1c in hemodialysis patients: Should one size fit all? Clin J Am Soc Nephrol
5: 15391541.
Joy, M., Cefahe, W., Hogan, S., et al. 2002. Long-term glycemic control measurements in diabetic patients
receiving hemodialysis. Am J Kidney Dis 39: 297307.
Kasiske, B., Lakatua, J., Ma, J., et al. 1998. A meta-analysis of the effects of dietary protein restriction on the
rate of decline in renal function. Am J Kidney Dis 31: 954961.
Kawazu, S., Tomono, S., Shimizu, M., et al. 1994. The relationship between early diabetic nephropathy and
control of plasma glucose in non-insulin dependent diabetes mellitus. The effect of glycemic control on
the development and progression of diabetic nephropathy in an eight year follow-up study. J Diabetes
Complicat 8: 1317.
Kazempour-Ardebil, S., Tam, F., Lecamwasam, V., et al. 2009. Assessing glycemic control in maintenance
hemodialysis patients with type 2 diabetes. Diabetes Care 32: 11371142.
Khaodhiar, L., Cummings, S., Apovian, C. 2009. Treating diabetes and prediabetes by focusing on obesity
management. Curr Diab Rep 9: 348354.
King, A. and Levey, A. 1993. Dietary protein and renal function. J Am Soc Nephrol 3: 17231737.
Kock, K.1999. Diabetic gastropathy: Gastric neuromuscular dysfunction in diabetes mellitus: A review of
symptoms, pathophysiology and treatment. Dig Dis Sci 44: 10611075.
Kontessis, P., Jones, S., Dodds, R., et al. 1990. Renal, metabolic and hormonal responses to ingestion of animal
and vegetable proteins. Kidney Int 38: 136144.
Kopple, J. 2004. Nutritional management of nondialyzed patients with chronic renal failure. In Kopple, J.D. and
Massry, S.G. (Eds.), Nutritional Management of Renal Disease, 389404. Philadelphia, PA: Lippincott
Williams & Wilkins.
Kris-Etherton, P. 1999. Monounsaturated fatty acids and risk of cardiovascular disease. Circulation 100: 12531258.
Loon, N. 2003. Diabetic kidney disease: Preventing dialysis and transplantation. Clinical Diabetes 21: 5562.
Ma, J., Rayner, C., Jones, K., et al. 2009. Diabetic gastroparesis: Diagnosis and management. Drugs 69:
971986.
Mak, R. 1991. Intravenous 1,25dihyroxycholecalciferol corrects glucose intolerance in hemodialysis patients.
Kidney Int 41: 10491054.
Mak, R. and DeFonzo, R. 1992. Glucose and insulin metabolism in uremia. Nephron 61: 377382.
Diabetes Management 211
Makoff, R. 1991. Water-soluble vitamin status in patients with renal disease treated with hemodialysis or peri-
toneal dialysis. J Renal Nutr 1: 5673.
Margett, B., Beilin, L., Vandongen, R., et al. 1986. Vegetarian diets in mild hypertension: A randomized con-
trolled trial. Br Med J 293: 14681471.
McDougall, K., Borman, D., Mitchell, E. 2001. Diabetes care in the dialysis setting. National Kidney
Foundation. Renal Link. 2: 16 (Summer).
Morelli, E., Loon, N., Meyer, T., et al. 1990. Effects of converting enzyme inhibition on the barrier function in
diabetic glomerulopathy. Diabetes 39: 7682.
Morioka, T., Tahara, H., Emoto, M., et al. 2001. Glycemic control is a predictor of survival for diabetic patients
on hemodialysis. Diabetes Care 24: 909913.
Muhlhauser, I., Toth, G., Sawicki P., et al. 1991. Severe hypoglycemia in type I diabetic patients with impaired
kidney function. Diabetes Care 14: 344346.
Munden, J. and Foley, M. (Eds.). 2007. Diabetes Mellitus: A Guide to Patient Care. Philadelphia, PA: Lippincott
Williams, & Wilkins. pp. 180222.
Nathan, D., Holman, R., Buse, J., et al. 2006. Management of hyperglycemia in type 2 diabetes: A consensus
algorithm for the initiation and adjustment of therapy. Diabetes Care 29: 19631972.
Nathan, D., Schoenfeld, D., Kuenen, J., et al. 2008. Translating the A1c assay into estimated average glucose
values. Diabetes Care. 31: 14731478.
National Diabetes Fact Sheet. 2008. Department of Health and Human Services, Centers for Disease Control
and Prevention.
National Kidney Foundation. 2000. K/DOQI clinical practice guidelines for nutrition in chronic renal failure.
Am J Kidney Dis 35: S40S43.
National Kidney Foundation. 2004. National Kidney Foundation: K/DOQI clinical practice guidelines of
hypertension and antihypertensive agents in chronic kidney disease. http://www.kidney.org/profession-
als/KDOQI/guidelines_bp/guide_8.htm (accessed September 11, 2010).
National Kidney Foundation. 2007. KDOQI clinical practice guidelines and clinical practice recommendations
for diabetes and chronic kidney disease. Am J Kidney Dis 49: S22S23.
Parkman, H., Hasler, W., Fisher, R. 2004. American Gastroenterological Association technical review on the
diagnosis and treatment of gastroparesis. Gastroenterology 127:15921622.
Parrish, C. 2007. Nutrition concerns for the patient with gastroparesis. Curr Gastrolenterol Rep 9: 295302.
Patrick, A. and Epstein, O. 2008. Review article: Gastroparesis. Aliment Pharmacol Ther 27: 724740.
Pedrini, M., Levey, A., Lau, J., et al. 1996. The effect of dietary protein restriction on the progression of diabetic
and nondiabetic renal diseases: A meta-analysis. Ann Intern Med 124: 627632.
Ravelli, A., Ledermann, S., Bissett, W., et al. 1992. Foregut motor function in chronic renal failure. Arch Dis
Child 67: 13431347.
Ritz, E. and Orth, S. 1999. Nephropathy in patients with type 2 diabetes mellitus. N Engl J Med 341: 11271133.
Sacks, F., Sretkey, L., Vollmier, W., et al. 2001. Effects on blood pressure of reduced dietary sodium and the
dietary approaches to stop hypertension (DASH) diet. N Engl J Med 344: 310.
Sheard, N. and Clark, N. 2000. The role of nutrition therapy in the management of diabetes mellitus. Nutr Clin
Care 3: 334348.
Shrishrimal, K., Hart, P., Franklin, M. 2009. Managing diabetes in hemodialysis patient: Observations and
recommendations. Cleve Clin J Med 76: 649655.
Skyler, J., Howard, B., Bergenstal, R. 2009. Intensive glycemic control and the prevention of cardiovascular
events: Implications of the ACCORD, ADVANCE and VA diabetes trial. A Position Statement of the
American Diabetes Association and a Scientific Statement of the American College of Cardiology foun-
dation and the American heart Association. Diabetes Care 32: 187192.
Steiner, G. 1999. Risk factors for macrovascular disease in type 2 diabetes. Diabetes Care 22: C6C9.
Tkac, I. 2009. Effect of intensive glycemic control on cardiovascular outcomes and all-cause mortality in type
2 diabetes: Overview and meta analysis of five trials. Diabetes Res Clin Pract 865: S57S62.
UK Prospective Diabetes Study Group. 1998. Intensive blood glucose control with sulphonylurea or insu-
lin compared with conventional treatment and risk of complications in patients with type 2 diabetes
(UKPDS 33). Lancet 352: 837853.
U.S. Department of Agriculture and the U.S. Department of Health and Human Services. 2010. Part A:
Executive Summary on the Dietary Guidelines for Americans. http://www.cnpp.usda.gov/Publications/
DietaryGuidelines/2010/DGAC/Report/A-ExecSummary.pdf
U.S. Renal Data System, USRDS. 2009. Annual data report: Atlas of chronic kidney disease and end-stage renal
disease in the United States. National Institutes of Health, National Institute of Diabetes and Digestive
and Kidney Diseases, Bethesda, MD.
212 Nutrition Therapy for Chronic Kidney Disease
Walker, J., Dodds, R., Murrells, T., et al. 1989. Restriction of dietary protein and progression of renal failure in
diabetic nephropathy. Lancet 334: 14111415.
Wanner, C., Krane, V., Marz, W., et al. 2005. Atorvastatin in patients with type 2 diabetes mellitus undergoing
hemodialysis. N Engl J Med 353: 238248.
Wild, S., Roglic, G., Green A., et al. 2004. Global prevalence of diabetes: Estimates for the year 2000 and
projections for 2030. Diabetes Care 27: 10471053.
Williams, A., Baker, F., Walls, J. 1987. Effect of varying quantity and quality of dietary protein intake in experi-
mental renal disease in rats. Nephron 46: 8390.
Williams, M. 2010. The role of glycemic control in diabetic ESRD patients. Renal and Urology News, March
2010, 227.
Williams, M., Lacson, E., Wang, W., et al. 2010. Glycemic control and extended hemodialysis survival in
patients with diabetes mellitus: Comparative results of traditional and time-dependent cox model analy-
sis. Clin J Am Soc Nephrol 5: 15951601.
Williams, M.E. 2009. Management of diabetes in dialysis patients. Curr Diab Rep 9: 466472.
Wisconsin Diabetes Advisory Group. 2008. Wisconsin diabetes mellitus essential care guidelines. http://dhs.
wisconsin.gov/health/diabetes/guidelines.htm (accessed September 7, 2010).
Wiseman, M., Hunt, R., Goodwin, A., et al. 1987. Dietary composition and renal function in healthy subjects.
Nephron 46: 3742.
Wolk, R., Moore, E, Foulks, C. 2007. Renal disease. The A.S.P.E.N. Nutrition Support Core Curriculum.
Wright, J., Wang, C., Kennedy-Stephenson, J., et al. 2003. Dietary intake of ten key nutrients for public health,
United States: 19992000. Advance data from Vital and Health Statistics; no. 334, Hyattsville, Maryland:
National Center for Health Statistics.
Wrone, E., Mercedes, C., Palaniappan, L., et al. 2003. Association of dietary protein intake and microalbu-
minuria in healthy adults: Third national health and nutrition examination survey. Am J Kidney Dis 41:
580587.
Zeller, K., Whittaker, E., Sullivan, L., et al. 1991. Effect of restricting dietary protein on the progression of renal
failure in patients with insulin-dependent diabetes mellitus. N Engl J Med 324: 7884.
16 Anemia Management
Emily Dill McDonald
WJB Dorn VA Medical Center
CONTENTS
16.1 Introduction........................................................................................................................... 213
16.1.1 Definition................................................................................................................... 213
16.2 Pathophysiology..................................................................................................................... 214
16.3 Specific Patient Populations................................................................................................... 215
16.4 Complications........................................................................................................................ 215
16.5 Evaluation.............................................................................................................................. 215
16.6 Treatment of Anemia............................................................................................................. 216
16.6.1 Goals of Therapy....................................................................................................... 216
16.6.2 Iron Therapy.............................................................................................................. 217
16.6.3 ESA Therapy............................................................................................................. 220
16.7 Nonpharmacological Treatment............................................................................................ 222
16.7.1 l-Carnitine................................................................................................................. 222
16.7.2 Ascorbic Acid (Vitamin C)........................................................................................ 223
16.7.3 Androgens..................................................................................................................224
16.7.4 B12/Folate...................................................................................................................224
16.7.5 Multivitamins............................................................................................................ 225
16.7.6 Other.......................................................................................................................... 225
16.8 Summary............................................................................................................................... 226
References....................................................................................................................................... 226
16.1 INTRODUCTION
Anemia is a common complication of chronic kidney disease (CKD) of any cause. (Besarab and
Levin, 2000). A study published in 2004 showed that 28% of Americans with mild CKD (stages
13) have anemia, and 87% of those with severe CKD (stages 4 and 5) have anemia (Guralnik et al.,
2004). If anemia remains untreated, patients may experience a variety of complications. Published
literature reveals that pre-dialysis CKD patients with anemia have an increased risk of morbidity
and mortality related to cardiac disease and stroke (Levin, 2003). Because of the long-term effects
of untreated anemia, it is important to be able to identify and treat patients appropriately with this
potentially serious complication of CKD.
16.1.1 Definition
Anemia is a reduction in one of the red blood cell (RBC) measurements, which include hemoglobin
(Hgb), hematocrit (hct), and/or RBC (Beutler and Waalen, 2006). Hgb measures the concentration
of oxygen-carrying protein in the blood; the normal range is 1317 g/dL. Hct is the percent of RBCs
in whole blood; the normal range is 36%50% (Beutler and Waalen, 2006). Finally, RBC is the
number of actual RBCs in a specific volume of whole blood; the normal range considered to be 46
213
214 Nutrition Therapy for Chronic Kidney Disease
million cells/mL. Although there are several ways to measure anemia, most guidelines published by
healthcare organizations define it using Hgb values.
Patients whose Hgb levels are below the fifth percentile of the normal range as reported by the
National Health and Nutrition Examination Surveys (NHANES) database are considered anemic;
each set of guidelines varies slightly with its definition (Astor et al., 2002; NKF-K/DOQI, 2006).
Because several factors can affect Hgb values, it is important to note that these guidelines pertain to
adult patients aged at least 18 years or older and patients of all races. For further discussion of these
variables, see Section 16.3.
The World Health Organization (WHO) defines anemia as an Hgb level less than 13 g/dL in
males and less than 12 g/dL in females (WHO, 2001). The European Best Practice Guidelines
(EBPG) consider males less than 70 years old with a Hgb level less than 13 g/dL or males at least
70 years old or older with a Hgb level of less than 12 g/dL to be anemic. EBPG considers females
anemic if the Hgb level is less than 11.5 g/dL (Locatelli et al., 2004). Finally, National Kidney
Foundation Kidney Disease Outcomes Quality Initiative (NKF-K/DOQI) defines anemia as a
Hgb level less than 12 g/dL in females and less than 13.5 g/dL in males (K/DOQI 2006). These
guidelines are very close in their definitions, but because there are variations, it is important to note
which guidelines are used for diagnosing when evaluating patients.
16.2 PATHOPHYSIOLOGY
There are several contributing factors that affect a patients Hgb level and ultimately cause anemia
in patients with CKD. The lifespan of the RBC in a healthy, non-CKD patient is 120 days. The
lifespan of the RBC decreases by almost half, to an estimated 60 days, in a stage 5 CKD patient
secondary to uremia (Hillman and Finch, 1996).
In addition to uremia, patients with CKD are more likely to have nutrient deficiencies com-
pared to their non-CKD counterparts. These deficiencies are worsened in hemodialysis because
nutrients are often removed from the blood during this process. Of note, hemodialysis patients are
also at risk for blood loss, exacerbating the anemia initially caused by the inability to produce a
sufficient supply of RBC. The most common nutrient deficiencies are B12, folate, and iron defi-
ciencies(NKF-K/DOQI, 2006). These nutrients are important in the production of RBCs, so a
deficiency compounds the primary cause of anemia and ultimately worsens the risk and extent of
anemia in CKD patients.
Although uremia and nutrient deficiencies can contribute to anemia in a CKD patient, the
most common cause of anemia in this population is a decrease in erythropoietin production
(McGonigle et al., 1984; NKF-K/DOQI, 2006; Radtke et al., 1979). Erythropoietin is an endog-
enous hormone produced by the kidneys that is responsible for the division and differentiation
of erythroid progenitor cells. In addition, it is responsible for the release of reticulocytes from
the bone marrow into the bloodstream (McGonigle et al., 1984; NKF-K/DOQI, 2006; Radtke
et al., 1979). Due to the nature of the disease, CKD patients experience a loss of functioning
renal mass (McGonigle et al., 1984), which ultimately causes the decrease in erythropoietin hor-
mone production. Published data shows that patients with CKD are unable to produce sufficient
erythropoietin to maintain normal Hgb levels. For example, a non-CKD patient responds to low
oxygenation by increasing erythropoietin production, but this same compensatory response is not
seen in CKD patients (Erslev, 1991).
Literature further explores the correlation between kidney function and anemia, most specifi-
cally the severity of anemia to the duration and extent of kidney dysfunction. Typically, patients
develop anemia when the estimated glomerular filtration rate (eGFR) falls below 60 mL/min/1.73
m2 (Astor et al., 2002; McClellan et al., 2004; NKF-K/DOQI, 2006). As CKD progresses, the
risk of anemia becomes much greater. The NHANES survey showed the prevalence of anemia
increased from 1% in patients with an eGFR of 60 mL/min/1.73 m2 to 9% at an eGFR of 30 mL/
min/1.73 m2 and, ultimately, to a prevalence of 33%67% at an eGFR of 15 mL/min/1.73 m2 (Astor
Anemia Management 215
et al., 2002). Anephric patients with the most severe kidney dysfunction correlate with the low-
est Hgb levels (Eschbach et al., 1967). KDOQI recommends all patients with an eGFR < 60 mL/
min/1.73 m2 be evaluated for anemia because severity correlates with eGFR.
16.4 COMPLICATIONS
The signs and symptoms of anemia vary based on severity of the loss of Hgb and also the rate at
which the anemia evolved. Patients with CKD typically develop anemia gradually over time; thus,
the rate of decline in Hgb does not result in symptoms in this patient population as frequently as
with other causes of acute anemia. Ultimately, CKD patients with anemia develop symptoms due to
decreased oxygen delivery to tissues.
Most patients with anemia experience fatigue, reduced exercise tolerance, and shortness of
breath (Levin, 1999; Locatelli et al., 2004; Ritz and Eisenhardt, 2000). Overall, these symptoms
affect patients quality of life greatly; therefore, this patient population is at an increased risk for
developing depression. Furthermore, several published studies indicate an increase in hospitaliza-
tions, cardiovascular disease, hospital length of stay, and increase in mortality in pre-dialysis CKD
patients (Collins et al., 2001; Dharmarajan et al., 2008; Levin, 1999; Locatelli et al., 2004; Ritz and
Eisenhardt, 2000).
As previously mentioned, severe cardiac complications are also associated with anemia. Research
shows that anemia both directly and indirectly worsens cardiac function and the symptoms of heart
failure in these patients (Levin et al., 1996; USRDS, 2008). The ANCHOR trial found an association
with an increase in mortality associated with Hgb levels less than 1314 mg/dL as compared to Hgb
levels of greater than 1617 mg/dL (Go et al., 2006). These potentially life-altering and even fatal
outcomes must be identified early and managed aggressively to prevent these severe complications.
16.5 EVALUATION
Since anemia is a known complication from CKD with potentially fatal consequences, the NKF-K/
DOQI guidelines recommend monitoring a patients Hgb at least annually. Furthermore, the guide-
lines recommend that a patient with worsening or unstable CKD or who have a history of a previous
decline in Hgb levels should be monitored more frequently (NKF-K/DOQI, 2006, 2007).
Patients who are identified as anemic based on the aforementioned guidelines should undergo
a thorough workup. Anemia in CKD is most commonly diagnosed by excluding other potential,
nonrenal causes of anemia and evaluating the progression and severity of a patients CKD (NKF-K/
DOQI, 2006). This should include the identification or ruling out of other possible causes of ane-
mia, such as bleeding, especially of the gastrointestinal (GI) tract as shown by a stool guaiac test
(Goddard et al., 2000; NKF-K/DOQI, 2006). Nutrition deficiencies, malignancies, human immuno-
deficiency virus (HIV), or other deficiencies may result in anemia as well. It is especially important
216 Nutrition Therapy for Chronic Kidney Disease
to investigate additional causes of anemia when the severity of the anemia is disproportionate to
the renal dysfunction and/or when a patient experiences leukopenia or thrombocytopenia (NKF-K/
DOQI, 2006, 2007).
To evaluate the other potential causes of anemia, several lab tests should be evaluated. A com-
plete blood count shows a patients Hgb, hct, and RBC and, in addition, shows the white blood
cell count (WBC), platelets, reticulocytes, mean corpuscular Hgb (MCH), and mean corpuscular
volume (MCV) (Goddard et al., 2000; Morris and Davey, 1996). WBCs and platelets should be
reviewed to determine whether other blood disorders are contributing to the anemia. A normal
reticulocyte value indicates that the bone marrow is functioning adequately (Morris and Davey,
1996; NKF-K/DOQI, 2006; Wish, 2006).
MCH shows the average amount of oxygen-carrying Hgb in a RBC. RBCs that are larger (macro-
cytic) are most likely to have a higher MCH; whereas, RBCs that are smaller (microcytic) are most
likely to have a lower MCH (hypochromic) (Goddard et al., 2000).
MCV indicates the average volume of the RBC; normal MCV is 80100 fL (Morris and Davey,
1996). RBCs that are within this range are termed normocytic. Microcytic indicates an MCV value
less than 80 fL, while macrocytic is defined by a value greater than 100 fL. Iron deficiency or
genetic Hgb, formation disorders result in anemias that are microcytic. Macrocytic anemia is usu-
ally associated with B12/folate deficiency (Goddard et al., 2000; Morris and Davey, 1996).
Most patients with an anemia due to chronic disease, including CKD, are normochromic and
normocytic (NKF-K/DOQI, 2006). Although erythropoietin deficiency is the primary cause of ane-
mia in CKD, the literature does not support evaluating erythropoietin levels. These levels do not
help distinguish between the causes of anemia (McGonigle et al., 1984; Radtke et al., 1979).
By evaluating these lab results, the cause and severity of the anemia most likely can be identified.
The Hgb, instead of hct, is the best indicator for the severity of the anemia (K/DOQI, 2006). Hgb
is more stable and can be measured directly. Conversely, hct is unstable and is usually affected by
extended storage and changes in temperature (Morris and Davey, 1996). Also, the measure of hct is
not standardized. Some literature indicates that hct can be affected by increase in serum glucose,
which further affects its instability (Van Duijnhoven and Treskes, 1996).
Although Hgb is a stable measure, there can be a dilutional affect (NKF-K/DOQI, 2006; WHO,
2001). This is not a major concern for nonhemodialysis patients or for peritoneal dialysis patients,
but it should be taken into consideration with patients on hemodialysis.
Iron deficiency is the most common cause of treatment failure in anemic patients, and it
should be considered when evaluating a patients lab work. The lab work for iron deficiency
includes: ferritin, transferrin, iron levels, and transferrin saturation (TSAT) (NKF-K/DOQI,
2006; Wish, 2006). TSAT and ferritin are used to evaluate the availability of iron for erythro-
poiesis. TSAT is an estimate of the amount of iron immediately available for delivery to the bone
marrow. It is calculated by finding the ratio of iron to total iron binding capacity and is reported
as a percentage. Ferritin is an indirect measure of iron storage (Wish, 2006). It is important to
note that ferritin can be affected by liver disease, infection, and inflammation, which can cause
a false elevation and mask a possible depletion. Finally, transferrin is the carrier of iron from
storage to the bone marrow for incorporation into RBC; it can be affected by a persons poor
nutrition (Wish, 2006).
2006). This published data encompasses dialysis (peritoneal and hemodialysis) and nondialysis
patients.
Along with this data, further evidence shows little benefit and possibly even harm with regard
to morbidity and mortality if the targeted Hgb is 13 g/dL or higher (Clement et al., 2009; K/DOQI,
2006; Palmer et al., 2010; Phrommintikul et al., 2007). It was because of this data that NKF-K/
DOQI guidelines were revised in 2007 to reflect a change in the recommended Hgb target range.
Those recommendations were to treat to a goal Hgb range of 1112 g/dL but not to exceed 13 g/dL
(Collins et al., 2001). More recent recommendations based on an Food and Drug Administration
(FDA) Safety Alert are to treat to a goal Hgb of 1011 g/dL (FDA Drug Safety Communication:
Modified dosing recommendations to improve the safe use of erythropoiesis-stimulating agents
[ESAs] in chronic kidney disease, June 24, 2011).
Although the Hgb range of 1011 g/dL is recommended by the guidelines, it is relatively dif-
ficult to maintain patients within this narrow window because of variables related to the laboratory
and the individual treatment response of patients. The FDA previously recommended aiming for
a Hgb range of 1012 g/dL (USFDA, 2007b). They joined KDOQI in the recommendation to not
exceed a Hgb of 13 g/dL. The FDA has placed alerts with regard to Hgb range in product labeling
for ESAs.
Treatment of anemia has both short-term and long-term effects. Increasing oxygencarrying
capacity by increasing Hgb ultimately decreases shortness of breath and fatigue, increases energy,
and improves the patients quality of life (Foley et al., 2009; Hampl et al., 2002; Silverberg, 2003).
Published literature shows that patients who reach an Hgb of at least 11 g/dL have improvement in
all-cause mortality, stabilization of left ventricular hypertrophy (LVH), fewer hospitalizations, and
improving quality of life (Hampl et al., 2002; Silverberg, 2003).
Increasing dietary intake of iron may be an option as adjunctive therapy for certain patients.
Foods containing heme iron have increased bioavailability of iron because it is absorbed better than
other sources of iron (Bothwell, 1995; Halberg, 1981). Heme iron sources include poultry, fish, and
ground beef. Nonheme iron sources also provide iron, but the absorption is about 33%50% less
than from heme sources. Iron-fortified foods, lentils, beans, and spinach are examples of nonheme
iron sources (Bothwell, 1995; Halberg, 1981).
Furthermore, other nutrients may indirectly affect iron absorption from food. Ascorbic acid may
increase the absorption of iron (Siegenberg et al., 1994). In contrast, food containing phenols (tea),
phytates (bran), polyphenols (berries and bright colored vegetables), and calcium (dairy) may inhibit
or decrease iron absorption (Siegenberg et al., 1994; see Table 16.1).
There are several options for oral iron replacement, which vary by formulation and amount of
elemental iron. To treat an iron deficiency, the goal iron dose from oral supplements should be 200
mg of elemental iron daily (NKF-K/DOQI, 2006). The formulations include ferrous sulfate, fuma-
rate and gluconate, and polysaccharide iron complex. Depending on the formulation, oral iron must
be taken from once daily to up to three times daily in order to reach the elemental iron intake goal
(Fishbane, 2007). Ferrous sulfate is the least expensive formulation but requires more frequent dos-
ing at three times daily to achieve this goal of 200 mg of elemental iron per day (Fishbane, 2007;
see Table 16.2).
Oral iron may be more convenient for a nonhemodialysis patient because it can be administered
at home, thereby preventing extra visits to the medical center for administration. Unfortunately,
the side effects typically limit the efficacy and increase the risk of treatment failure with this class
of medications. The most common side effects are those of the GI tract, most often constipation
(Fishbane, 2007; NKF-K/DOQI, 2006). Other GI side effects include cramping, nausea, and diar-
rhea (Lexi-Comp, 2011). Patients should be educated that stools may become darker and harder due
to the increase in iron (Fishbane, 2007; Lexi-Comp, 2011). It is important to note that the incidence
of GI side effects increases as the dose increases. Reducing the dose or changing formulations may
reduce the incidence of these side effects (Fishbane, 2007; NKF-K/DOQI, 2006). Furthermore,
because the side effects, especially constipation, may be worse in the elderly population, it is advised
to limit the dose to ferrous sulfate 325 mg daily in this patient population (Fick et al., 2003).
Ensuring appropriate absorption of the elemental iron is important to achieve maximum effects
from this supplementation. An acidic environment is needed to achieve the greatest absorption of
iron. Patients should be educated to take their iron supplementation in between meals; bedtime
administration may be effective in minimizing the effects from food. Antacids such as histamine-2
(H2) receptor antagonists and proton pump inhibitors will further inhibit the absorption from this
medication (Fishbane, 2007; Lexi-Comp, 2011). Products with calcium will have similar effects in
minimizing the acidic environment and affecting iron absorption (Lexi-Comp, 2011). Unfortunately,
TABLE 16.1
Foods and Dietary Intake Affecting Iron Absorption
Effect Food and/or Nutrient Mechanism
Increase Poultry, fish, ground beef Direct source of heme iron
absorption Greater bioavailability versus nonheme iron
Beans, lentils, spinach Direct source of nonheme iron
Ascorbic acid (vitamin C) Indirectly via improving absorption of iron
from food
Decrease Tea (phenols) Indirectly inhibits absorption of iron from food
absorption Bran (phytates)
Berries and bright colored vegetables (polyphenols)
Dairy (calcium)
Anemia Management 219
TABLE 16.2
Oral Iron Formulations (Recommended Goal Dose: 200 mg of Elemental Iron)
Strength of Tablet (Amount Elemental Iron Percentage Availability
Iron Formulation Brand Name of Elemental Iron) (mg/g) of Drug of Elemental Iron (%)
Ferrous sulfate Ferrous sulfate 325 mg (65 mg) 200 20
Fer-Gen-Sol 125 mg (25 mg)
Fer-In-Sol 125 mg (25 mg)
Feratab 300 mg (60 mg)
Ferrous fumarate Ferrous fumarate 325 mg (107 mg) 330 33
Hemocyte 324 mg (106 mg)
NephroFer 350 mg (115 mg)
Feostat 100 mg (33 mg)
Ferrous gluconate Ferrous gluconate 325 mg (36 mg) 120 11
Fergon 225 mg (27 mg)
Iron polysaccharide Niferex-150 150 mg (150 mg) 1000 100
Ferrex-150 150 mg (150 mg)
Niferex 50 mg (50 mg)
the effects of food on iron absorption may limit its usefulness in preventing or minimizing potential
GI side effects.
The newer formulations of iron, such as polysaccharide iron complex and heme iron polypeptide,
were developed to decrease the administration frequency, to maximize iron absorption in the GI
tract, and to potentially limit the GI side effects. At this time, data shows that patients on these for-
mulations do meet treatment goals, but there is limited information comparing older versus newer
formulations with regard to efficacy and adverse events (Fishbane and Besarab, 2007). Ferrous
sulfate is less expensive and should be used as initial iron replacement therapy. If a patient is unable
to tolerate one formulation, then it is appropriate to try others.
If a patient is unable to take oral iron for any reason, or if he has consistent IV access and makes
regular visits to a doctors office (usually hemodialysis patients), IV iron is an option for replacement
therapy. IV iron therapy is also appropriate in patients who do not meet their goal TSAT and ferritin
levels after 2 months of oral iron or if the target Hgb range is not met with use of ESAs (NKF-K/
DOQI, 2006).
The three IV iron formulations are iron dextrin, ferric gluconate, and iron sucrose. These medi-
cations are given infrequently, and the doses are much larger than those of oral iron. Prior to starting
IV iron, patients should be evaluated for underlying infection or inflammatory diseases, as these
patients are not candidates for this route of administration (Canziani et al., 2001; Parkkinen et al.,
2000). Because of safety concerns, ferric gluconate and iron sucrose are preferred over iron dextran
(NKF-K/DOQI, 2006).
Iron dextran is the oldest of the three formulations, and it has a significantly higher incidence of
anaphylaxis and other side effects compared to the other two formulations. Since there is the risk of
serious side effects, iron dextran requires a test dose prior to administering the maintenance dose
(Fishbane, 2003). Typical iron dextran doses are 5001000 mg/dose repeated as needed to replete
stores appropriately (Charytan et al., 2001; Michael et al., 2002).
Ferric gluconate and iron sucrose can be dosed anywhere from 100 to 400 mg per dose and
repeated as needed to replete stores (Fishbane, 2007; Silverberg, 2003). Although these formula-
tions do not have as high a risk of anaphylaxis as iron dextran and do not require a test dose, precau-
tions should be taken and there should be close monitoring for potential adverse events (Fishbane,
2003; NKF-K/DOQI, 2006).
220 Nutrition Therapy for Chronic Kidney Disease
The most common side effect of all IV-iron formulations is hypotension, which can be mini-
mized by administering a lower dose or slowing the rate of administration (Fishbane, 2003). Other
side effects include nausea and vomiting, which also can be minimized by slowing the rate (Michael
et al., 2002). Unfortunately, the more serious side effects such as anaphylaxis and iron overload
cannot be avoided by changing the rate of administration. Should a patient experience these events,
intervention must be made to prevent serious harm to the patient. Iron overload is a serious risk
typically seen when iron is administered when a patients ferritin is greater than 800 ng/mL
(NKF-K/DOQI, 2006; Morris and Davey, 1996). It is especially noted with IV iron because of
the high iron load given at one time. Ultimately, deposits form and cause dysfunction of the liver,
pancreas, and heart (NKF-K/DOQI, 2006; Parkkinen et al., 2000). Should a patient experience iron
overload, deferoxamine or phlebotomy should be used. Although the actual risk of iron overload is
not well studied, there have not been data to show added benefit when ferritin levels are greater than
500 ng/mL (NKF-K/DOQI, 2006).
Precautions against infection and inflammation should be taken when considering treatment with
IV iron (Canziani et al., 2001; Parkkinen et al., 2000). These symptoms can be a sign of infection
or chronic oxidative stress. Although somewhat controversial, there are data stating that exposure to
iron increases a patients risk of bacterial infections (Canziani et al., 2001; Parkkinen et al., 2000).
The data proposes that because bacteria uses iron for cellular functioning, administration of IV iron
in high doses will worsen the acute state. Guidelines recommend withholding iron supplements for
a patient during an infectious state (NKF-K/DOQI, 2006).
Another controversial debate surrounding iron therapy is the increase in oxidative stress created
by the replacement. Authors propose that this increase in oxidative stress can worsen cardiovascular
disease (Agarwal et al., 2004; Kletzmayr and Horl, 2002). At this time, there is no evidence to show
that iron replacement increases a patients risk of morbidity or mortality. Further research is needed
prior to making recommendations on this concern.
Monitoring iron therapy should include iron labs (ferritin, iron levels, transferring, and TSAT)
monthly during initial treatment. Once the patient is stable, monitoring can be extended to 3-month
intervals. As stated earlier, KDOQI states that the goal of hemodialysis patients is ferritin of >200
ng/mL and a TSAT of >20% (NKF-K/DOQI, 2006; Silverberg, 2003). Nonhemodialysis patients
and peritoneal dialysis patients should aim for a ferritin of >100 ng/mL and also a TSAT of >20%
(NKF-K/DOQI, 2006).
These goals should be closely monitored to ensure there is sufficient iron for RBC production and
to decrease the patients risk for iron overload. Again, there are no data to show added benefit with
a ferritin level greater than 500 ng/mL (NKF-K/DOQI, 2006). It is also important to note that once
a patients iron has been repleted, iron replacement must be continued, especially with concomitant
use of ESA therapy. ESA therapy will stimulate an increase in RBC production, thus increasing
iron consumption.
to improve patients cardiac health (Fink et al., 2001; Revicki et al., 1995). Most recent reports have
shown an improvement in cardiovascular outcomes when patients anemia is treated with ESAs.
Because the benefit can be so great, the FDA recommends CKD patients with a Hgb less than
10 mg/dL should be evaluated for the use of ESA therapy (Clement et al., 2009; USFDA, 2007b). If
patients have an active malignancy or a history of malignancy, then ESAs should be initiated with
caution. Again, ESA therapy should not be initiated until any iron deficiency has been corrected.
The lowest possible dose in order to achieve a goal Hgb range of 1012 mg/dL should be used
(Clement et al., 2009; USFDA, 2007b).
Drug options available in the United States, which increase erythropoiesis include epoetin alpha
(Procrit and Epogen) and darbepoetin (Aranesp) (USFDA, 2007b). Epoetin beta is not available
in the United States. Both medications have the same site of action, and both are proteins created to
mimic the endogenous hormones produced by the kidneys. Because of the slight difference in dar-
bepoetins structure compared to that of epoetins, darbepoetin has a higher molecular weight. This
increased weight extends its duration of action; thus, epoetin is referred to as short-acting, whereas
darbepoetin is referred to as long-acting.
Both medications can be administered IV or subcutaneously (Ateshkadi et al., 1993). Subcuta
neousdosing is usually chosen based on its convenience for patients, specifically patients not on
dialysis who do not visit the clinic regularly. IV epoetin is most commonly used in hemodialysis
patients because it can be administered during their hemodialysis sessions, decreasing the need
for additional needle sticks. Epoetin is usually administered one to three times weekly. Current
literature shows that patients respond to therapy similarly with each dosing interval (McGowan
etal., 2008; Provenzano et al., 2005). Darbepoetin can be administered weekly or every other week
(Suranyi et al., 2003). Recently, the dosing interval of darbepoetin was extended to monthly dosing,
without affecting the response to therapy (Jadoul et al., 2004).
Epogen is usually dosed based on vial size; the typical starting dose is Epogen 10,000 units weekly
or 20,000 units every other week. Should a patients Hgb prior to treatment be greater than 10 mg/
dL, a provider should use clinical judgment with regard to possibly starting a lower dose (Table 16.3).
The most common side effects with either of these formulations are hypertension and seizures
(Phrommintikul et al., 2007; Vaziri, 1999). These are typically associated with an increased rate of
rise of the Hgb. Thus, patients should be monitored closely upon initiating ESA therapy in order to
appropriately monitor the effects of the ESA on Hgb.
Hypertension is a potentially serious side effect of ESA medications, and patients should be
monitored closely for changes in blood pressure (NKF-K/DOQI, 2006). Hypertension is more com-
monly seen in dialysis patients than nondialysis patients, but owing to potential complications, all
patients with uncontrolled hypertension should be cautiously started on ESAs. It is not a contrain-
dication, but measures should be taken to better monitor and control the blood pressure. KDOQI
TABLE 16.3
Comparison of Epoetin Alpha to Darbepoetin
Epoetin alpha Darbepoetin
Brand Name Procrit or Epogen Aranesp
Route of Administration Subcutaneous (SQ) or IV SQ or IV
Half-life (IV 413 h 21 h (IV)
administration) 49 h (SQ)
Time to Onset of Full 23 weeks 26 weeks
Effect
Dosing Frequency Three times weekly to weekly Every other week to monthly
Side Effects Injection site reaction, nausea/vomiting, Injection site reaction, nausea/vomiting,
hypertension, stroke, seizures hypertension, stroke, seizures
222 Nutrition Therapy for Chronic Kidney Disease
guidelines recommend withholding ESA therapy based on blood pressure only when the hyperten-
sion does not respond to antihypertensive therapy.
Another serious side effect with ESA therapy is the risk of thromboembolism and/or stroke
(Phrommintikul et al., 2007). This side effect is more often associated with ESA use when a patients
Hgb is above the range of 1012 g/dL (Clement et al., 2009; USFDA, 2007b). ESAs should not be
administered in patients with a Hgb greater than 13 g/dL (Clement et al., 2009; Fishbane, 2007;
Ofsthun et al., 2003; USFDA, 2007b; Wish, 2006). This was the reason for the FDAs Black Box
Warning, issued in 2007. The warning reads, In clinical studies, patients experienced greater risks
for death, serious cardiovascular events, and stroke when administered erythropoiesis-stimulating
agents (ESAs) to target hemoglobin levels of 13 g/dL and above. Individualize dosing to achieve and
maintain hemoglobin levels within the range of 1011 g/dL. Again, patients should be monitored
closely to minimize this adverse event (Clement et al., 2009; USFDA, 2007b).
This warning is located in the package insert of all ESA medications. Along with close monitor-
ing of actual Hgb levels, the package inserts provide guidance on the rate of rise of the Hgb. The
manufacturers recommend a maximum rate of 1 g/dL rise in Hgb over a 2-week period. Should the
rate exceed this recommendation, then the ESA dose should be reduced by 25%. On the contrary,
if the rate of rise is not at least 1 g/dL over 4 weeks, then the dose should be increased by 25%
(Clement et al., 2009; USFDA, 2007b). These recommendations and guidelines reiterate the impor-
tance of checking an Hgb every 2 weeks until stable.
As stated above, monitoring of ESAs focuses primarily on the Hgb values. Initially, a patients
Hgb should be checked every 2 weeks. Once the Hgb is stable, the time period for checking the Hgb
is extended to every 4 weeks. The importance of checking the Hgb so often centers on prevention of
potentially serious side effects and ensuring an appropriate response to therapy.
Although recommendations have been made to check the Hgb at least every 2 weeks initially, it
is important to note that in order to see the maximum effects from a certain dose, the appropriate
time must be given for the increase in erythropoiesis and RBC production rate. This can take as few
as 4 weeks or up to 16 weeks. Therefore, adjustments for doses of ESA medications should not occur
more often than every 24 weeks (Clement et al., 2009; Collins, 2002; USFDA, 2007b).
Along with Hgb monitoring, other routine labs should be drawn, such as iron labs, B12/folate, and
thyroid function studies. These do not need to be drawn monthly once stable but, again, should be
monitored on a periodic basis.
Some patients may have resistance to ESA therapy despite constant monitoring and dose adjust-
ments. These patients should have a thorough workup to review the possibilities for infection,
inflammation, blood loss, aluminum toxicity, elevated parathyroid hormone, hypothyroidism, and
malnutrition specifically related to B12 and folate (NKF-K/DOQI, 2006). The most common reason
for ESA resistance is iron deficiency. Thus, iron should be replete prior to initiating ESA therapy
(Fernandez-Rodriguez et al., 1999; NKF-K/DOQI, 2006).
Unfortunately, despite proper monitoring and dose adjustments, some patients fail therapy. Prior
to determining that a patient has failed ESA therapy, the provider must ensure that the patients iron
is replete. Furthermore, the patient should have received adequate dosing of ESA therapy for at least
46 months. Adequate dosing is defined as 450 units/kg/week with IV administration or 300 units/
kg/week with subcutaneous administration. Even after reaching the therapeutic range for the Hgb, a
patient is at risk of failing ESA treatment should the Hgb not remain in the desired range (NKF-K/
DOQI, 2006).
The mechanism in which l-carnitine contributes to anemia is unknown. Several reports postulate
that carnitine is necessary for increased formation of colony-forming-unit erythroid in the bone
Anemia Management 223
marrow; this has been reported in mice (Kitamura et al., 2005). Another speculation is that carni-
tine is necessary for the RBC phospholipid membrane. When this component is reduced or absent,
the RBC becomes deformed and is very fragile, which ultimately reduces the half-life of the cell
(Eknoyan et al., 2003).
Hemodialysis patients are thought to be especially at risk of a deficient carnitine state. There is
also speculation that CKD patients, nondialysis, and dialysis patients, have a reduction in activity in
the pathway required to convert acyl coA to acyl carnitine, ultimately creating a deficiency (Evans,
2003). This deficiency may contribute to anemia in CKD patients via the pathways previously dis-
cussed. In order to correct this deficiency, l-carnitine has been used in dialysis patients to treat
anemia, with or without concomitant ESA therapy (Eknoyan et al., 2003; Evans, 2003).
The adverse events associated with l-carnitine are minimal, but some patients have reported
seizures with IV l-carnitine (Kitamura et al., 2005). Researchers are concerned with potential
accumulation of harmful products of l-carnitine metabolism (Bain et al., 2006; Evans, 2003). Small
studies using oral l-carnitine doses ranging from 0.5 to 2 g daily for up to 3 years have not shown
harm to the patients; these doses were well tolerated (Golper et al., 2003). There is not current evi-
dence comparing IV versus oral l-carnitine.
It is important to note that d-carnitine and dl-carnitine should not be used. d-carnitine is not
used for fatty acid metabolism; thus, it will not affect the RBC membrane. dl-carnitine has been
associated with neuromuscular dysfunction(McGowan et al., 2008).
A study published by Kooistra showed an association with anemic dialysis patients requiring
higher doses of epoetin therapy when the serum free carnitine levels were low (Kooistra et al.,
1991). Other small studies, randomized and nonrandomized, show that patients have an improve-
ment in hct or Hgb with l-carnitine administration, and at times a decrease in ESA doses is required
to maintain a therapeutic Hgb (Hurot et al., 2002; Kooistra et al., 1991). On the other hand, data
from randomized, placebo-controlled trials show no significant difference in Hgb for anemic dialy-
sis patients.
Should a dialysis patient not respond to conventional therapy, it is reasonable to try l-carnitine
(McGowan et al., 2008). KDOQI guidelines for nutrition in adult anemia patients recommend oral
or IV l-carnitine 1 g after dialysis (NKF-K/DOQI, 2000). Patients should be assessed every 3
months for response to therapy; l-carnitine should be discontinued at 912 months if no response
(Evans, 2003). The NKF Carnitine Consensus Conference noted concern over the use of oral car-
nitine due to unknown risks associated with its breakdown in the GI tract (Evans, 2003). Overall,
KDOQI guidelines for anemia state that there is insufficient evidence to support use of l-carnitine
in anemia due to CKD (NKF-K/DOQI, 2000, 2006). Again, the hesitation pertains to the small size
and poor study designs of the trials supporting use of l-carnitine.
saturation. Despite the significant findings, there was no report on specific patient outcomes and
few reports of adverse events. In addition, the studies were small, which limits the power of the
outcomes (Deved et al., 2009). There have been some randomized controlled trials with ascorbic
acid in dialysis patients. Most of the data are conflicting and, again, side effects were commonly not
reported (Attallah et al., 2006; Keven et al., 2003).
Because adverse events are rarely reported in the studies, the safety and long-term efficacy with
oral or IV ascorbic acid is unknown. The primary concern about the use of ascorbic acid is the
potentially harmful pro-oxidant effects (Chen et al., 2003). Ascorbic acid may increase oxalate
in the body, which can create crystals with different cations, such as calcium and iron (Canavese
etal., 2005). These crystals could potentially affect organs should they accumulate. This effect
may be seen with either IV or oral administration. Because of this concern, some authors of tri-
als recommend using IV ascorbic acid only in patients unable to achieve target Hgb levels with
adequate iron stores and sufficient epoetin doses (Ballal et al., 1991; Sezer et al., 2002; Tarng and
Huang, 1998).
Furthermore, these trials were with dialysis patients and used IV ascorbic acid with doses rang-
ing from 100 to 500 mg. These trials usually assessed patients for response after 8 weeks, and then
therapy was discontinued (Ballal et al., 1991; Sezer et al., 2002; Tarng and Huang, 1998). Based on
the trial designs, if a patient receives ascorbic acid for treatment of anemia, then it should be admin-
istered intravenously and for a short duration.
The K/DOQI guidelines state there is insufficient evidence to support use of ascorbic acid. The
EBPGs state that use of ascorbic acid to correct ascorbic acid levels may reduce the hyporesponsive-
ness to epoetin and/or treatment with iron for iron deficiency.
16.7.3 Androgens
Before the development of ESAs, androgens were used regularly in the treatment of anemia.
Androgens were thought to possibly increase endogenous erythropoietin production, sensitivity of
erythroid progenitor cells to erythropoietin, and possibly increase RBC survival (Sheashaa et al.,
2005). Currently, there is very limited data to support the use of androgens in conjunction with
ESAs or instead of ESAs. Potential side effects of androgens include acne, priapism, liver dysfunc-
tion, and hepatocellular carcinoma (Eussen et al., 2005; Gaughan et al., 1997). The risk of androgen
use outweighs the benefits, especially in women (NKF-K/DOQI, 2006).
Current guidelines, including K/DOQI and the European Best Practices Guidelines, state that
the risks with androgens outweigh the potential, limited benefit. K/DOQI states that androgens
should not be used in treatment of anemia in CKD.
16.7.4 B12/Folate
As mentioned previously, a deficiency in B12 and folate may cause anemia and potentially worsen
anemia due to CKD. The treatment of macrocytic anemia due to folate and/or B12 deficiency
can be treated through several different avenues (see Evaluation for more information on
diagnosis.).
B12 (cyanocobalamin) can be replaced both orally and parenterally. Replacement doses are much
higher than the recommended dietary intake of B12 (Kuzminski et al., 1998). Literature shows that
patients respond equally to both oral and intramuscular administration (Bolaman et al., 2003; Butler
et al., 2006). Parenteral B12 injections are given in doses of 1000 mcg (Kuzminski et al., 1998).
During initial treatment, the doses are administered daily and are titrated downward over time.
After this phase, doses are administered monthly until the deficit is corrected (Delpre et al., 1999).
Injections are a good option for patients with compliance concerns.
The use of oral formulations is limited by compliance and absorption. To ensure appropriate
absorption, high doses of oral B12 should be used at doses of 10002000 mcg daily (Bolaman et al.,
Anemia Management 225
2003). Other options for B12 replacement are sublingual and nasal spray, although data are limited
(Cunningham et al., 1981; Slot et al., 1997). With either route of administration, B12 treatment has
few adverse events and is inexpensive (Butler et al., 2006).
Once B12 treatment has been initiated, then folic acid should also be replaced if patient is consid-
ered deficient (USFDA, 2007a). Although the recommended daily intake of folic acid is 200 mcg/
day, the recommended dose for replacement therapy is 15 mg daily; the most common dose is 1
mg daily. Folic acid replacement is administered orally for at least 1 month up to 4 months. Some
reports have associated folic acid treatment with malignancies, so treatment should be limited to
appropriate use in a deficiency (USDA, 2009). Because the replacement doses of B12 and folate are
much higher than the recommended dietary intake, these doses are rarely found in over-the-counter
multivitamins (Table 16.4).
16.7.5 Multivitamins
Malnutrition does contribute to anemias, especially in CKD patients. Unfortunately, several factors
can contribute to malnutrition in CKD patients. These factors include a decrease in oral intake due
to a change in taste, anorexia, depression, or dislike for the restricted diets required due to their
renal disease (NKF-K/DOQI, 2000, 2006). Many CKD patients must restrict their intake of protein,
which is a major source of dietary iron (NKF-K/DOQI, 2000). Furthermore, dialysis patients are at
risk of malnutrition for the reasons stated above, which is worsened by the affects of dialysis itself.
Dialysis removes nutrients, especially water-soluble vitamins, and also causes blood loss. Dialysis
patients are also in a higher catabolic state, which increases the use of nutrients (NKF-K/DOQI,
2000).
Because they are at risk for loss of water-soluble vitamins, dialysis patients should be moni-
tored closely for deficiencies. There are special formulations of vitamin supplements that take into
consideration CKD patients. These formulations contain vitamin B, vitamin C, and folic acid. It
is important to note that there are currently no data supporting regular vitamin therapy other than
supplementation to correct deficiencies.
16.7.6 Other
Patients who are symptomatic and anemic, especially those with blood loss, should be considered
for blood transfusions. The risk of transfusions, such as infections and fluid overload, should be
discussed at length with patients. The risks should also be weighed versus the benefits; thus, the
recommendation is to use transfusion only in symptomatic patients (NKF-K/DOQI, 2006).
TABLE 16.4
Comparison of Treatment for Common Nutritional Deficiencies
Nutrient Deficiency Therapy Adjunctive Therapy
Iron Hemodialysis Consider increasing dietary iron intake but
IV iron with dialysis sessions use caution with other dietary restrictions,
CKD (nondialysis) or peritoneal dialysis especially in patients with kidney disease.
Oral irona See Table 16.1
B12 Dose = 1000 2000 mcg Fish, poultry, eggs
Route: IM, oral, sublingual, or intranasal
Folate 1 mg daily by mouth Leafy green vegetables, whole grains
Doesthepatienthaveadiagnosisof
CKDbasedonguidelines?
(WHO,EBPG,K/DOQI)
NO YES
UseofESAsisnotindicatedin
Reviewpatientfornutritionaldeficiencies
thispatient.MonitorCBCannually
suchasironandB12/folate
unlesskidneyfunctiondeclinesor
becomesunstable
MCV>100fL
MCV< 100fL
MCV80100fL
EvaluateB12andfolate
AssessTSATandferritin.Startiron levels.Initiatetherapy
therapyifferritin<500 ng/mL asappropriate.
SeeTable16.4
Goaloftreatment:
-TSAT20%
-Ferritin>100CKD, not on dialysis
> 100inperitonealdialysis
> 200inhemodialysis Ruleoutothercausesofanemiasuchas
(but notlimitedto)GIbleed,malignancy,
HIV, infection,andthyroiddisease
Ensurenutritionaldeficiencies
arecorrected
Startepoetin alfaordarbepoetin.
Monitorhemoglobin,bloodpressure,and
signs/symptomsofanemia
FIGURE 16.1 Work-up of anemia. Abbreviations: CBC, complete blood count; CKD, chronic kidney dis-
ease; ESA, erythropoietin-stimulating agents; GI, gastrointestinal; HIV, human immunodeficiency virus;
MCV, mean corpuscular volume; TSAT, transferrin saturation.
16.8 SUMMARY
Patients with CKD should be monitored closely for anemia (Figure 16.1). Should their Hgb values
fall below the desired range, a thorough workup to determine the underlying cause should be under-
taken. There are many treatment options to correct deficiencies of both hormones and nutrients. No
matter the course of treatment, all patients should be followed closely in order to prevent potentially
harmful and even fatal outcomes due to poorly controlled anemia.
REFERENCES
Agarwal, R., Vasavada, N., Sachs, N., et al. 2004. Oxidative stress and renal injury with intravenous iron in
patients with chronic kidney disease. Kidney Int. 65(6):22792289.
Astor, B., Muntner, P., Levin, A., et al. 2002. Association of kidney function with anemia: The Third National
Health and Nutrition Examination Survey (19881994). Arch Intern Med. 162(12):14011408.
Anemia Management 227
Ateshkadi, A., Johnson, C., Oxton, et al. 1993. Pharmacokinetics of intraperitoneal, intravenous and subcutane-
ous recombinant human erythropoietin in patients on continuous ambulatory peritoneal dialysis. Am J
Kidney Dis. 21(6):635642.
Attallah, N., Osman-Malik, Y., Frinak, S., et al. 2006. Effect of intravenous ascorbic acid in hemodialysis
patients with EPO-hyporesponsive anemia and hyperferritinemia. Am J Kidney Dis. 47(4):644654.
Bain, M., Faull, R., Milne, R., et al. 2006. Oral L-carnitine: Metabolite formation and hemodialysis. Curr Drug
Metab. 7(7):811816.
Ballal, S., Domoto, D., Polack, D., et al. 1991. Androgens potentiate the effects of erythropoietin in the treat-
ment of anemia of end-stage renal disease. Am J Kidney Dis. 17(1):2933.
Besarab, A., Amin, N., Ahsan, M., et al. 2000. Optimization of epoetin therapy with intravenous iron therapy in
hemodialysis patients. J Am Soc Nephrol. 11(3):530538.
Besarab, A. and Levin, A. 2000. Defining a renal anemia management period. Am J Kidney Dis. 36(6 Suppl
3):S13S23.
Beutler, E. and Waalen, J. 2006. The definition of anemia: What is the lower limit of normal of the blood hemo-
globin concentration? Blood 107(5):17471750.
Beutler, E. and West, C. 2005. Hematologic differences between African-Americans and whites: The roles
of iron deficiency and alpha-thalassemia on hemoglobin levels and mean corpuscular volume. Blood
106(2):740745.
Bolaman, Z., Kadikoylu, G., Yukselen, V., et al. 2003. Oral versus intramuscular cobalamin treatment in
megaloblastic anemia: A single-center, prospective, randomized, open-label study. Clin Ther. 25(12):
31243134.
Bosman, D., Winkler, A., Marsden, J., et al. 2001. Anemia with erythropoietin deficiency occurs early in dia-
betic nephropathy. Diabetes Care 24(3):495499.
Bothwell, T. 1995. Overview and mechanisms of iron regulation. Nutr Rev. 53(9):237245.
Bridges, K. and Hoffman, K. 1986. The effects of ascorbic acid on the intracellular metabolism of iron and
ferritin. J Biol Chem. 261(30):1427314277.
Butler, C., Vidal-Alaball, J., Cannings-John, R., et al. 2006. Oral vitamin B12 versus intramuscular vita-
min B12 for vitamin B12 deficiency: A systematic review of randomized controlled trials. Fam Pract.
23(3):279285.
Canavese, C., Petrarulo, M., Massarenti, P., et al. 2005. Long-term, low-dose intravenous vitamin C leads to
plasma calcium oxalate supersaturation in hemodialysis patients. Am J Kidney Dis. 45(3):540549.
Canziani, M., Yumiya, S., Rangel, E., et al. 2001. Risk of bacterial infection in patients under intravenous iron
therapy: Dose versus length of treatment. Artif Organs. 25(11):866869.
Charytan, C., Levin, N., Al-Saloum, M., et al. 2001. Efficacy and safety of iron sucrose for iron defi-
ciency in patients with dialysis-associated anemia: North American clinical trial. Am J Kidney Dis.
37(2):300307.
Charytan, C., Qunibi, W., and Bailie, G. 2005. Venofer Clinical Studies Group. Comparison of intravenous
iron sucrose to oral iron in the treatment of anemic patients with chronic kidney disease not on dialysis.
Nephron Clin Pract. 100(3):c55c62.
Chen, W., Lin, Y., Yu, F., et al. 2003. Effect of ascorbic acid administration in hemodialysis patients on in vitro
oxidative stress parameters: Influence of serum ferritin levels. Am J Kidney Dis. 42(3):158166.
Clement, F., Klarenbach, S., Tonelli, M., et al. 2009. The impact of selecting a high hemoglobin level on health-
related quality of life for patients with chronic kidney disease: A systematic review and meta-analysis.
Arch Intern Med. 169(12):11041112.
Collins, A. 2002. Influence of target hemoglobin in dialysis patients on morbidity and mortality. Kidney Int
Suppl. 80:4448.
Collins, A., Li, S., St. Peter, W., et al. 2001. Death, hospitalization and economic associations among incident
hemodialysis patients with hematocrit values of 36 to 39%. J Am Soc Nephrol. 12(11):24652473.
Cunningham, J., Sharman, V., Goodwin, F., et al. 1981. Do patients receiving haemodialysis need folic acid
supplements? Br Med J (Clin Res Ed). 282(6276):1582.
Delpre, G., Stark, P., and Niv, Y. 1999. Sublingual therapy for cobalamin deficiency as an alternative to oral and
parenteral cobalamin supplementation. Lancet 354(9180):740741.
Descombes, E., Hanck, A., and Fellay, G. 1993. Water soluble vitamins in chronic hemodialysis patients and
need for supplementation. Kidney Int. 43(6):13191328.
Deved, V., Poyah, P., James, M., et al. 2009. Ascorbic acid for anemia management in hemodialysis patients: a
systematic review and meta-analysis. Am J Kidney Dis. 54(5):10891097.
Dharmarajan, T., Pankratov, A., and Morris, E. 2008. Anemia: Its impact on hospitalizations and length of hos-
pital stay in nursing home and community older adults. J Am Med Dir Assoc. 9(5):354359.
228 Nutrition Therapy for Chronic Kidney Disease
Eknoyan, G., Latos, D., and Lindberg, J.2003. National Kidney Formation Carnitine Consensus Conference.
Practice recommendations for the use of l-carnitine in dialysis-related carnitine disorder. National
Kidney Foundation Carnitine Consensus Conference. Am J Kidney Dis. 41(4):868876.
Erslev, A. 1991. Erythropoietin. N Engl J Med. 324(19):13391344.
Eschbach, J., Downing, M., Egrie, J., et al. 1989. USA multicenter clinical trial with recombinant human eryth-
ropoietin (Amgen) results in hemodialysis patients. Contrib Nephrol. 76:160165.
Eschbach Jr., K., Funk, D., Adamson, J., et al. 1967. Erythropoiesis in patients with renal failure undergoing
chronic dialysis. N Engl J Med. 276(12):653658.
Eussen, S., de Groot, L., Clarke, R., et al. 2005. Oral cyanocobalamin supplementation in older people with
vitamin B12 deficiency: A dose-finding trial. Arch Inter Med. 165(10):11671172.
Evans, A. 2003. Dialysis-related carnitine disorder and levocarnitine pharmacology. Am J Kidney Dis. 41(4
Suppl 4):S13S26.
Fernandez-Rodriguez, A., Guindeo-Casasus, M., Molero-Labarta, T., et al. 1999. Diagnosis of iron deficiency
in chronic renal failure. Am J Kidney Dis. 34(3):508513.
Fick, D., Cooper, J., Wade, W., et al. 2003. Updating the Beers criteria for potentially inappropriate medi-
cation use in older adults: results of a US consensus panel of experts. Arch Intern Med. 163(22):
27162724.
Fink, J., Blahut, S., Reddy, M., et al. 2001. Use of erythropoietin before the initiation of dialysis and its impact
on mortality. Am J Kidney Dis. 37(2):348355.
Fishbane, S. 2003. Safety in iron management. Am J Kidney Dis. 41(Suppl 5):1826.
Fishbane, S. 2007. Iron management in nondialysis-dependent CKD. Am J Kidney Dis. 49(6):736743.
Fishbane, S. and Besarab A. 2007. Mechanism of increased mortality risk with erythropoietin treatment to
higher hemoglobin targets. Clin J Am Soc Nephrol. 2(6):12741282.
Foley, R., Curtis, B., and Parfrey, P. 2009. Erythropoietin therapy, hemoglobin targets and quality of life in
healthy hemodialysis patients: A randomized trial. Clin J Am Soc Nephrol. 4(4):726733.
Gaughan, W., Liss, K., Dunn, S., et al. 1997.A 6-month study of low-dose recombinant human erythropoietin
alone and in combination with androgens for the treatment of anemia in chronic hemodialysis patients.
Am J Kidney Dis. 30(4):495500.
Go, A., Yang, J., Ackerson, L., et al. 2006. Hemoglobin level, chronic kidney disease, and the risks of death and
hospitalizations in adults with chronic heart failure: The Anemia in Chronic Heart Failure: Outcomes and
Resource Utilization (ANCHOR) study. Circulation 113(23):27132723.
Goddard, A., McIntyre, A., and Scott, B. 2000. Guidelines for the management of iron deficiency anaemia.
British Society of Gastroenterology. Gut 46(Suppl 34):IV1IV5.
Golper, T., Goral, S., Becker, B., et al. 2003. l-carnitine treatment of anemia. Am J Kidney Dis. 41(4 Suppl
4):S27S34.
Guralnik, J., Eisenstaedt, R., Ferrucci, L., et al. 2004. Prevalence of anemia in persons 65 years and older in the
United States: Evidence for a high rate of unexplained anemia. Blood 104(8):22632268.
Halberg, L. 1981. Bioavailability of dietary iron in man. Annu Rev Nutr. 1:123147.
Hampl, H., Stenberg, C., Berweck, S., et al. 2002. Regression of left ventricular hypertrophy in hemodialysis
patients is possible. Clin Nephrol. 58(Suppl 1):S73S96.
Hillman, R. and Finch, C. 1996. Red Cell Manual. 7th edition. Philadelphia, PA: Davis.
Hurot, J., Cucherat, M., Haugh, M., et al. 2002. Effects of l-carnitine supplementation in maintenance hemo-
dialysis patients: A systematic review. J Am Soc Nephrol. 13(3):708714.
Jadoul, M., Vanrenterghem, Y., Foret, M., et al. 2004. Darbepoetinalfa administered once monthly maintains
haemoglobin levels in stable dialysis patients. Nephrol Dial Transplant. 19(4):898903.
Keven, K., Kutlay, S., Nergizoglu, G., et al. 2003. Randomized, crossover study of the effect of vitamin C on
EPO response in hemodialysis patients. Am J Kidney Dis. 41(6):12331239.
Kitamura, Y., Satoh, K., Satoh, T., et al. 2005. Effect of l-carnitine on erythroid colony formation in mouse
bone marrow cells. Nephrol Dial Transplant. 20(5):981984.
Kletzmayr, J. and Horl, W. 2002. Iron overload and cardiovascular complications in dialysis patients. Nephrol
Dial Transplant. 17(Suppl 2):2529.
Kooistra, M., Struyvenberg, A., and van Es, A. 1991. The response of recombinant human erythropoietin in
patients with the anemia of end-stage renal disease is correlated with serum carnitine levels. Nephron
57(1):127128.
Kuzminski, A., Del Giacco, E., Allen, R., et al. 1998. Effective treatment of cobalamin deficiency with oral
cobalamin. Blood 92(4):11911198.
Levin, A. 1999. How should anaemia be managed in pre-dialysis patients? Nephrol Dial Transplant.
14(Suppl2):6674.
Anemia Management 229
Levin, A. 2003. Clinical epidemiology of cardiovascular disease in chronic kidney disease prior to dialysis.
Semin Dial. 16(2):101105.
Levin, A., Singer, J., Thompson, C., et al. 1996. Prevalent left ventricular hypertrophy in the predialysis popula-
tion identifying opportunities for intervention. Am J Kidney Dis. 27(3):347354.
Lexi-Comp Online. February 2011. Pediatric Lexi-Drugs Online. Hudson, OH: Lexi-Comp, Inc.
Lipschitz, D., Bothwell, T., Seftel, H., et al. 1971. The role of ascorbic acid in the metabolism of storage iron.
Br J Haematol. 20(2):155163.
Locatelli, F., Aljama, P., Barany, P., et al. 2004. Revised European best practice guidelines for the management
of anaemia in patients with chronic renal failure. Nephrol Dial Transplant. 19(Suppl2):ii, 147.
McClellan, W., Aronoff, S., Bolton, W., et al. 2004. The prevalence of anemia in patients with chronic kidney
disease. Curr Med Res Opin. 20(9):15011510.
McGonigle, R., Wallin, J., Shadduck, R., et al. 1984. Erythropoietin deficiency and inhibition of erythropoiesis
in renal insufficiency. Kidney Int. 25(2):437444.
McGowan, T., Vaccaro, N., Beaver, J., et al. 2008. Pharmacokinetic and pharmacodynamic profiles of extended
dosing of epoetinalfa in anemic patients who have chronic kidney disease and are not on dialysis. Clin J
Am Soc Nephrol. 3(4):10061014.
Michael, B., Coyne, D., Fishbane, S., et al. 2002. Sodium ferric gluconate complex in hemodialysis patients:
Adverse reactions compared to placebo and iron dextran. Kidney Int. 61(5):18301839.
Morris, M. and Davey, F. 1996. Basic examination of blood. In Henry, J.B., ed. Clinical Diagnosis and
Management by Laboratory Methods. Philadelphia, PA: WB Saunders, 549593.
National Kidney Foundation (NKF) K/DOQI. 2000. Clinical Practice Guidelines for nutrition in chronic renal
failure. Am J Kidney Dis. 35(6 Suppl 2):S1S140.
National Kidney Foundation (NKF) K/DOQI. 2006. Clinical Practice Guidelines for anemia in chronic kidney
disease. Am J Kidney Dis. 47(5 Suppl 3):S11S145.
National Kidney Foundation (NKF) K/DOQI. 2007. Clinical Practice Guidelines and Clinical Practice
Recommendations for anemia in chronic kidney disease: 2007 Update of Hemoglobin Target. Am J
Kidney Dis. 50(3):471530.
Ofsthun, N., Labrecque, J., Lacson, E., et al. 2003. The effects of higher hemoglobin levels on mortality and
hospitalization in hemodialysis patients. Kidney Int. 63(5):19081914.
Palmer, S., Navaneethan, S., Craig, J., et al. 2010. Meta-analysis: Erythropoiesis-stimulating agents in patients
with chronic kidney disease. Ann Intern Med. 153(1):2333.
Parkkinen, J., von Bonsdorff, L., Peltonen, S., et al. 2000. Catalytically active iron and bacterial growth in
serum hemodialysis patients after intravenous iron-saccharate administration. Nephrol Dial Transplant.
15(11):18271834.
Phrommintikul, A., Haas, S., Elsik, M., et al. 2007. Mortality and target haemoglobin concentrations in
anaemic patients with chronic kidney disease treated with erythropoietin: A meta-analysis. Lancet
369(9559):381388.
Provenzano, R., Bhaduri, S., and Singh, A. 2005. PROMPT Study Group. Extended epoetinalfa dosing as
maintenance treatment for the anemia of chronic kidney disease: The PROMPT study. Clin Nephrol.
64(2):113123.
Radtke, H., Claussner, A., Erbes, P., et al. 1979. Serum erythropoietin concentration in chronic renal failure:
Relationship to degree of anemia and excretory renal function. Blood 54(4):877884.
Reed, W. and Diehl, L. 1991. Leukopenia, neutropenia and reduced hemoglobin levels in healthy American
blacks. Arch Intern Med. 151(3):501505.
Revicki, D., Brown, R., Feeny, D., et al. 1995. Health-related quality of life associated with recombi-
nant human erythropoietin therapy for predialysis chronic renal disease patients. Am J Kidney Dis.
25(4):548554.
Richalet, J., Soububielle, J., Atenzana, A., et al. 1994. Control of erythopoiesis in humans during prolonged
exposure to the altitude of 6,542m. Am J Physiol. 266(3 Pt 2):R756R764.
Ritz, E. and Eisenhardt, A. 2000. Early epoetin treatment in patients with renal insufficiency. Nephrol Dial
Transplant. 15(Suppl3):4044.
Ruiz-Arguelles, G. 2006. Altitude above sea level as a variable for definition of anemia. Blood. 108(6):2131;
author reply.
Sezer, S., Ozdemir, F., Yakupoglu, U., et al. 2002. Intravenous ascorbic acid administration for erythropoietin-
hyporesponsive anemia in iron loaded hemodialysis patients. Artif Organs. 26(4):366370.
Sheashaa, H., Abdel-Razek, W., El-Husseini, A., et al. 2005. Use of nandrolonedecanoate as an adjuvant
for erythropoietin dose reduction in treating anemia in patients on hemodialysis. Nephron Clin Pract.
99(40):c102c106.
230 Nutrition Therapy for Chronic Kidney Disease
Siegenberg, D., Baynes, R., Bothwell, T., et al. 1994. Ascorbic acid prevents the dose-dependent inhibitory
effects of polyphenols and phytates on nonheme-iron absorption. Am J Clin Nutr. 53(2):537541.
Silverberg, D. 2003. Outcomes of anaemia management in renal insufficiency and cardiac disease. Nephrol
Dial Transplant. 18(Suppl 2):ii, 712.
Slot, W., Merkus, F., Van Deventer, S., et al. 1997. Normalization of plasma vitamin B12 concentration by intra-
nasal hydroxocobalamin in vitamin B12-deficient patients. Gastroenterology 113(2):430433.
Stoves, J., Inglis, H., and Newstead, C. 2001. A randomized study of oral vs. intravenous iron supplementation
in patients with progressive renal insufficiency treated with erythropoietin. Nephrol Dial Transplant.
16(5):967974.
Suranyi, M., Lindberg, J., Navarro, J., et al. 2003. Treatment of anemia with darbepoetinalfa administered de
novo once every other week in chronic kidney disease. Am J Nephrol. 23(2):106111.
Tarng, D. and Huang, T. 1998. A parallel, comparative study of intravenous iron versus intravenous ascorbic
acid for erythropoietin-hyporesponsive anaemia in haemodialysis patients with iron overload. Nephrol
Dial Transplant. 13(11):28672872.
U.S. Department of Agriculture (USDA), Agricultural Research Service. 2009. USDA National Nutrient
Database for Standard Reference, Release 22. Nutrient Data Laboratory Home Page. Available at: http://
www.ars.usda.gov/ba/bhnrc/ndl
U.S. Food and Drug Administration (USFDA). February 2007a. Folic acid: Prescribing information. Silver
Spring, MD: U.S. Food and Drug Administration.
U.S. Food and Drug Administration (USFDA). March, 2007b. Epogen (epoetinalfa), procrit (epoetinalfa),
aranesp (darbepoetinalfa) for injection: Prescribing information. Silver Spring, MD: U.S. Food and Drug
Administration (USFDA).
U.S. Renal Data System (USRDS). 2008. Annual data report: Atlas of chronic kidney disease and end-stage
renal disease in the United States. Bethesda, MD: National Institutes of Health, National Institute of
Diabetes and Digestive and Kidney Diseases.
Van Duijnhoven, H. and Treskes, M. 1996. Marked interference of hyperglycemia in measurements of mean
(red) cell volume by Technicon H analyzers. Clin Chem. 42(1):7680.
Vaziri, N. 1999. Mechanism of erythropoietin-induced hypertension. Am J Kidney Dis. 33(5):821828.
Wish, J. 2006. Assessing iron status: beyond serum ferritin and transferrin saturation. Clin J Am Soc Nephrol.
1(Suppl 1):S4S8.
World Health Organization (WHO). 2001. Iron Deficiency Anemia: Assessment, Prevention and Control. A
Guide for Program Managers. Geneva, Switzerland: World Health Organization.
17 Enteral and Parenteral
Nutritional Support
Kyle Thompson
Appalachian State University
Lynn K. Thomas
University of South Carolina School of Medicine
CONTENTS
17.1 Introduction........................................................................................................................... 232
17.2 Definition and Purpose of Enteral Nutrition......................................................................... 232
17.2.1 Goals of EN Therapy................................................................................................. 232
17.2.2 Indications for EN...................................................................................................... 232
17.2.3 Delivery of EN Therapy............................................................................................ 233
17.2.4 Selection of Formula.................................................................................................. 233
17.2.4.1 Acute Kidney Injury................................................................................... 235
17.2.4.2 Chronic Renal Failure................................................................................. 235
17.2.4.3 Hemodialysis............................................................................................... 235
17.2.5 Administration of Enteral Formula........................................................................... 236
17.2.6 Monitoring and Adverse Reactions........................................................................... 236
17.2.7 Transitional Enteral Feedings.................................................................................... 237
17.3 Indications for Parenteral Nutrition....................................................................................... 237
17.3.1 Goals of Parenteral Nutrition..................................................................................... 238
17.3.2 Delivery of Parenteral Nutrition................................................................................ 238
17.3.3 Administration of Parenteral Nutrition..................................................................... 238
17.3.4 Monitoring Parenteral Nutrition................................................................................ 238
17.3.5 Adverse Reactions..................................................................................................... 239
17.3.6 Transitional Feedings................................................................................................. 239
17.4 Intradialytic Parenteral Nutrition: Introduction and Goal of Therapy.................................. 239
17.4.1 Definition...................................................................................................................240
17.4.2 Malnutrition: Causes and Management.....................................................................240
17.4.3 Criteria.......................................................................................................................240
17.4.4 Formulations.............................................................................................................. 241
17.4.5 Delivery Methods...................................................................................................... 241
17.4.6 Advantages and Disadvantages................................................................................. 242
17.4.7 Team Approach to Nutrition Support in Renal Disease............................................ 242
17.5 Conclusion............................................................................................................................. 243
References....................................................................................................................................... 243
231
232 Nutrition Therapy for Chronic Kidney Disease
17.1 INTRODUCTION
When renal dysfunction is present in a critically ill patient, intensive nutritional management
is required. Critically ill patients with renal disease tend to present as complicated cases, are
often malnourished, and may exhibit numerous nutrition-related metabolic aberrations. This
chapter discusses the practice of enteral and parenteral nutritional support in critically ill
patients with renal disease.
dialysis regimen and the possible presence of uremia should be considered as a source of eating
problems (Krenitsky, 2004).
If possible and prudent per patients condition, oral diet and oral supplementation should be attempted
prior to initiation of enteral feeding. If no trial of oral feeding is possible, in most cases the patient
should receive EN within 2448 h of entering the intensive care unit (ICU) (McClave et al., 2009).
TABLE 17.1
Daily Nutrient Requirements
Acute Kidney Injury CKD Dialysis
Fluids Output plus 500 ccs Restrict as necessary Output plus 1000 ccs
Energya 3035 kg 3035 kg 3035 kg
Proteinb 0.60.8 g/kg 0.60.75 g/kg 1.21.4 g/kg
Sodium 12 g 13 g 2g
Potassium Serum within normal Unrestricted unless elevated 2g
limits (WNL)
Calcium Serum WNL Serum WNL <2.0 g
Phosphorus Serum WNL 1012 mg/g/protein 1215 mg/g/protein
Vitamins/minerals Follow Recommended B-complex plus C, Ascorbic acid 60100 mg
Daily Allowance Individualized vitamin D, Pyridoxine 2 mg
(RDA) iron, and zinc B123 g
Vitamin E 15 IU
Zinc 15 mg
No vitamin A or K
Individualize vitamin D and
iron RDA others
b Increase amount if renal replacement therapy is used. Usually in the 1.01.7 g/kg/day range depending on the type
of therapy.
234 Nutrition Therapy for Chronic Kidney Disease
due to osmolalities, which are typically lower than those of disease-specific formulas (Mueller and
Bloch, 2008).
If nutrition assessment reveals no electrolyte irregularities which might require a disease-spe-
cific formula, the patient may be started on a standard enteral formula and monitored for fluid status
and electrolyte changes. If fluid volume is a concern, a 2-cal/mL formula may be selected to deliver
adequate nutrients in a smaller amount of formula (Wolk et al., 2007).
Hyperpotassemia, hypermagnesemia, and hyperphosphatemia are the most common issues that
prompt selection of a disease-specific formula (Marian and McGinnis, 2007).
Renal-specific enteral formulas are designed to provide lower intakes of magnesium, sodium,
phosphorus, and potassium compared to standard formulas (Chen and Peterson, 2009). See
Table17.2 for a comparison of renal-specific formulas to standard formulas.
Little research has been done to date regarding outcomes of standard formulas versus disease-
specific formulas (Chen and Peterson, 2009; Malone, 2005; Stratton et al., 2005; Table 17.2).
TABLE 17.2
Standard and Renal-Specific Formulas (Oral Supplement and Tube Feeding)
Calorie CHO PRO FAT PO4 Vitamin A %H2O
Product (s/mL) (g/L) (g/L) (g/L) Na K (mg/L) (mg/L) (IU) (L)
Boost 1.0 173 42 17.8 550 1690 1270 5400 85
(Nestle)
Boost 1.1 84 58.2 49 1099 1099 928 5063 85
Glucose
Control
(Nestle)
Boost Plus 1.5 190 59 58 720 1610 1270 5400 78
(Nestle)
Ensure 1.1 164 36 24 800 1480 1000 5000 83
(Abbott)
Ensure Plus 1.5 200 54.9 53.3 880 2114 840 5000 68
(Abbott)
Glucerna 1.5 133 82.5 75 1380 2520 1000 8660 76
(Abbott)
Nepro 1.8 161 81 96 1060 1060 720 3180 73
(Abbott)
Novasource 2 200 74 100 9001600 8101100 650 3300 70
Renal
(Nestle)
Nutren 2 205 70 104 740 1256 700 4996 70
Renal
(Nestl)
Re/Gen HP/ 2 261 67 67 1000 1277 377 n/a n/a
HC Shelf
Stable
(Nutra/
balance)
Suplena 1.8 196 45 96 802 1137 717 3165 74
Carb Steady
(Abbott)
Enteral and Parenteral Nutritional Support 235
17.2.4.3 Hemodialysis
For hemodialysis patients, prescribe either a standard formula or a renal-specific formula as
indicated by the results of the nutritional assessment. If a standard formula is indicated, consider
a standard high-protein formula due to the increased protein losses associated with dialysis. All
standard formulas are low in sodium, but keep in mind any potassium and phosphorus restrictions
when using the high-protein formulas (Malone, 2005).
TABLE 17.3
Classification/Staging System for Acute Kidney Injurya
Stage Serum Creatinine Urine Output Criteria
1 Increase in serum creatinine of more than or equal to 0.3 mg/dL Less than 0.5 mL/kg/h for more than 6 h
(26.4 mol/L) or increase to more than or equal to 150%200%
(1.5- to 2-fold) from baseline
2b Increase in serum creatinine to more than 200%300% (>2- to Less than 0.5 mL/kg/h for more than 12 h
3-fold) from baseline
3c Increase in serum creatinine to more than 300% (>3-fold) from Less than 0.3 mL/kg/h for 24 h or anuria
baseline (or serum creatinine of more than or equal to 4.0 mg/dL for 12 h
[354 mol/L] with an acute increase of at least 0.5 mg/dL [44
mol/L])
a Modified from RIFLE (Risk, Injury, Failure, Loss, and End-stage kidney disease) criteria. The staging system proposed is
a highly sensitive interim staging system and is based on recent data indicating that a small change in serum creatinine
influences outcome. Only one criterion (creatinine or urine output) has to be fulfilled to qualify for a stage.
b 200%300% increase = 2- to 3-fold increase.
c Given wide variation in indications and timing of initiation of renal replacement therapy (RRT), individuals who receive
RRT are considered to have met the criteria for stage 3 irrespective of the stage they are in at the time of RRT.
Source: Mehta, R., et al., 2007 Crit. Care., 11, R31R39, 2007.
236 Nutrition Therapy for Chronic Kidney Disease
TABLE 17.4
Suggested Minimal Monitoring
Weigh every other day until stable then weekly for acute care and monthly for long-term care. Daily weights may be
required in intensive care settings and for dialysis patients.
Basic electrolytes plus calcium, magnesium, and phosphorous, complete blood count initially then every 10 days. Do
more frequently in intensive care situations. Do monthly or at least quarterly in long-term care and in the dialysis
clinic.
Albumin initially, then every month. Other more frequent assays and monitoring parameters are used in intensive
care.
Monitor glucose readings until feeding or nutrition support is at final rate and blood sugars are stable.
Check inputs and outputs according to unit policies.
The patients clinical course should be monitored (Table 17.4), including overall medical condi-
tion, overall nutrition status, medications, concurrent therapies, and discharge planning (Wolk etal.,
2007).
As the patient progresses through the continuum of care, it is important to consider nutritional
factors that may affect the patient in subsequent nutrition care settings. Collaboration of nutrition
care with future caregivers, including clinicians in acute care facilities, case managers/social work-
ers, long-term care providers, homecare staff, and family members will help to ensure a smoother
transition for the patient to other care settings. If the patient receives regular hemodialysis, the renal
dietitian who works with the patient at the dialysis center may provide valuable assistance in ensur-
ing optimal nutrition care throughout the nutrition-care process.
The patients clinical course should be monitored, including overall medical condition, overall
nutrition status, medications, concurrent therapies, and discharge planning (Wolk et al., 2007).
Monitoring the patient for coordination of care issues is similar to that of the patient receivingEN.
If the patients condition permits, it is to the patients advantage to transition to enteral/oral
feedings as soon as possible. Monitoring of traditional nutrition parameters, such as appetite and
diet records (if the patient is consuming oral nutrients), are helpful in determining an appropriate
timetable for transitioning to gastrointestinal feedings.
17.4.1 Definition
IDPN is a solution of carbohydrate, amino acids, lipids, electrolytes, and vitamin/minerals that is
infused during a patients usual dialysis treatments. It is usually administered during the last 90 min of
treatment. The delivery schedule is based on the premise that extra parenteral nutrients can be delivered
and excess fluids extracted with no change in the dialysis regimen. It is thought that IDPN can be used
as an aggressive clinical strategy to reverse malnutrition in the stage 5 CKD patient (Pupim et al., 2002).
Intraperitoneal nutrition (IPN) is similar to IDPN. This type of therapy is used to help improve
hypoalbuminemia in patients receiving peritoneal dialysis. Protein and amino acid losses in the
dialysate can reach 15 g/day. These losses contribute to chronic malnutrition (Wang et al., 2003).
IPN solution replaces a portion of the glucose dialysate for one or two exchanges each day when
continuous ambulatory peritoneal dialysis is being used. For patients using continuous cycler-
assisted peritoneal dialysis, the IPN can be added to the last fill or given as a manual exchange
during the day. Twenty to forty grams of amino acids can be administered to counteract daily losses
and provide additional protein to reverse malnutrition (Fuhrman, 2009).
17.4.3 Criteria
To be eligible for IDPN, all previous trials of oral and enteral therapy must have failed. An inad-
equate nutrition status must be evidenced by persistent, severe protein malnutrition or severe energy
Enteral and Parenteral Nutritional Support 241
TABLE 17.5
Typical Measures to Determine Nutritional Status
Monthly Quarterly Biannual As needed
Stabilized serum albumin Percent of standard body Subjective global Prealbumin
weight or normal body assessment
mass index (10%
weight loss over 3
months)
Percent of usual post treatment Dietary interview Stabilized serum creatinine or
weight urea nitrogen
nPNA (protein equivalent of total Skin fold thickness or mid-arm
nitrogen appearance) muscle area, circumference
malnutrition with significant weight loss. K/DOQI Nutrition Guideline 19 outlines indications
for nutritional support (Kopple, 2000). The indications include a documented period of inadequate
intake, evidence of failed dietary therapy, and the need to combine IDPN with current oral intake to
meet daily nutrient needs. Table 17.5 contains the typical biochemical and anthropometric measure-
ment parameters used to justify the use of IDPN.
Inclusion criteria are similar for Medicare and most private insurers. The official Medicare lan-
guage states: If the medical record, including the judgment of the attending physician, indicates
the impairment will be long and indefinite duration, the test of permanence is met. Unless there are
contraindications, there must be a reasonable trial of both oral and enteral nutrition if the gastroin-
testinal tract is functional. (Medicare Manual, 2010).
IPN can be provided, according to K/DOQI guidelines, for peritoneal dialysis patients who are
malnourished and consume inadequate energy and protein. They must be unable to tolerate an ade-
quate oral diet or tube feeding. Inclusion criteria generally follow the standards set by the Centers
for Medicare and Medicaid Services.
17.4.4 Formulations
IDPN solutions are typically 5001000 mL in total volume. They are packaged as a 2-in-1 (dextrose
and amino acids) or 3-in-1 (dextrose, amino acids, and lipids) admixtures. These mixtures can also
contain vitamins, minerals, and electrolytes if needed. The admixtures are formulated to provide
between 500 and 1200 calories and 1.21.4 g protein/kg (Wolk et al., 2007). Concentrations vary
according to tolerance and considerations of chronic diseases such as diabetes mellitus (Table 17.6).
Intravenous lipids are the most challenging of the macronutrients secondary to the potential for
free-fatty-acid toxicity. In the serum, free fatty acids are bound to the albumin. Therefore, patients
with low albumin levels have increased concentrations of unbound free fatty acids, which can cause
cardiac and pulmonary injuries (How and Lau, 2004; Table 17.4).
IPN solutions contain the usual dialysate and amino acids based on the patients usual peritoneal
exchange prescription. For example, an amino acid solution of 1.5% would provide 30 g of protein
in a 2 L volume of 2.5% dextrose (Fuhrman, 2009).
TABLE 17.6
Typical IDPN Formulations
Prescriptiona Total Volume (mL) Formula Composition = Calories Total Calories
250 mL D50 500 125 g dextrose = 425 525
250 mL 10% AA 25 g protein = 100
250 mL D70 800 175g dextrose = 595 815
550 mL 10% AA 55 g protein = 220
250 mL D50 950 125 g dextrose = 425 1025
500 mL 10% AA 50 g protein = 200
200 mL 20% lipids 200 mL lipids= 400
250 mL D30 975 75 g dextrose =255 905
500 mL 10% AA 50 g protein = 200
225 mL 20% lipids 225 mL lipids = 450
17.5 CONCLUSION
The provision of nutrition support to renal patients is similar to the provision of nutrition support
to patients with normal kidney function. Renal patients require additional monitoring to promote
maintenance of appropriate metabolic parameters. Skilled intervention by dietetics professionals is
essential to achieving excellent outcomes in these complicated patients.
REFERENCES
Barber J., Rollins, C., Sacks, G. 2007. Parenteral nutrition formulations. In The A.S.P.E.N. Nutrition Support
Core Curriculum. Silver Spring, MD: American Society for Parenteral and Enteral Nutrition, 277299.
Boost, Boost Plus, Boost Glucose Control, Novasourse Renal, and Nutren Renal. Available at: www.
nestle-nutrition.com/products (accessed January 2011).
Burrowes, J., Alto, A., Kaufman, A. 1993. Intradialytic parenteral nutrition: A practical approach. Am Nephrol
Nurses Assoc J. 20:671677.
Cano, N., Aparicio, M., Brunori, G., et al. 2009. ESPEN guidelines on parenteral nutrition: Adult renal failure.
Clin Nutr. 28:401414.
Cano, N., Fouque, D., Roth, H., et al., and the French Study Group for Nutrition in Dialysis. 2007. Intradialytic
parenteral nutrition does not improve survival in malnourished hemodialysis patients: A 2 year multi-
center, prospective, randomized study. Am Soc Nephrol. 18:25832591.
Charney, P. 2004. Parenteral nutrition in kidney disease. In L. Byham-Gray, and K. Wiesen, (Eds.), A Clinical
Guide to Nutrition Care. Chicago, IL: American Dietetic Association, Renal Practice Group, 151158.
Charney, P. and Charney, D. 2002. Nutrition support in renal failure. Nutr Clin Pract. 17:226235.
Chen, Y. and Peterson, S. 2009. Enteral Nutrition formulas: Which formula is right for your adult patient? Nutr
Clin Pract. 24:344.
Chertow, G. Ling, J. Lew, N., et al. 1994. The association of intradialytic parenteral nutrition administration
with survival in hemodialysis patients. Am J Kidney Dis. 24:912920.
Dezfuli, A., Scholl, D., Lindenfield, S., et al. 2009. Severity of hypoalbuminemiapredicts response to intradia-
lytic parenteral nutrition in hemodialysis patients. J Renal Nutr. 19:291297.
Druml, W. 2010. Nutrition support in acute renal failure. In Handbook of Nutrition and the Kidney, Sixth
Edition. Philadelphia, PA: Lippincott Williams & Wilkins, Wolters Kluwer, 84.
Druml, W. and Kierdorf, H. 2009. Parenteral nutrition in patients with renal failure. The German Association
for Nutritional Medicine. German Medical Science v. 7. doi: 10.3205/000070 (accessed January 12,
2011).
Ensure, Ensure Plus, Glucerna, Nepro, and Suplena. Available at: www.abbott.com/products (accessed
January 2011).
Fuhrman, M. 2004. Parenteral nutrition in kidney disease. In L. Byham-Gray, and K. Wiesen, (Eds.), A Clinical
Guide to Nutrition Care. Chicago, IL: American Dietetic Association, Renal Practice Group, 158174.
Fuhrman, M. 2009. Intradialytic parenteral nutrition and intraperitoneal nutrition. Nutrit Clin Pract. 24:470480.
How, P. and Lau, A. 2004. Intradialytic parenteral nutrition. Pharmacotherapy 24:1218.
Kopple, J. 1999. Therapeutic approaches to malnutrition in chronic dialysis patients: The different modalities
of nutritional support. Am J Kidney Dis. 33:180185.
Kopple, J. for the K/DOQI Nutrition Work Group Membership. 2000. National Kidney Foundation. Kidney
disease outcomes quality initiative: Clinical practice guidelines for nutrition in chronic renal failure. Am
J Kidney Dis. 35 (suppl. 2):S17S104.
Krenitsky, J. 2004. Nutrition in renal failure: Myths and management. Pract Gastroenterol. 20:4059.
Kumpf, V. and Gervasio, J. 2007. Complications of parenteral nutrition. In Gottschlich, M. (Ed.), The A.S.P.E.N.
Nutrition Support Core Curriculum. Silver Spring, MD: American Society for Parenteral and Enteral
Nutrition, 323339.
Malone, A. 2005. Enteral formula selection: A review of selected product categories. Pract Gastroenterol. 28:
4574.
Marian, M., and McGinnis, C. 2007. Overview of enteral nutrition. In M. Gottschlich (Ed.), The A.S.P.E.N.
Nutrition Support Core Curriculum. Silver Spring, MD: American Society for Parenteral and Enteral
Nutrition, 187208.
McCann, L., Feldman, C., Hornberger, J. 1999. Effect of intradialytic parenteral nutrition on delivered Kt/V.
Am J Kidney Dis. 33:11311135.
244 Nutrition Therapy for Chronic Kidney Disease
McClave, S., Martindale, R., Vanek, V., et al. 2009. Guidelines for the provision and assessment of nutrition
support therapy in the adult critically ill patient. J Parenter Enteral Nutr. 33 (3):277316.
Medicare Manual. 2010. Medicare National Coverage Determinations Manual. Chapter 1, Part 3, Section
180.2. Revision 113, 0219-10. Available at: www.cms.gov/manuals/downloads/ncd103c1_Part3.pdf
Mehta, R., Kellum, J., Shah, S., et al. 2007. Acute kidney injury network: Report of an initiative to improve
outcomes in acute kidney injury. Crit Care. 11:R31R39.
Moore, E., and Lindenfield, S. 2007. Intradialytic parenteral nutrition: A nutrition support intervention for high
risk malnutrition in chronic kidney disease. Support Line. 29:616.
Mortelmans, A., Duym, P., Vanderbroucke, J., et al. 1999. Intradialytic parenteral nutrition in malnourished
hemodialysis patients; a prospective long-term study. J PEN. 23:9095.
Mueller, C. and Bloch, A. 2008. Intervention: Enteral and parenteral nutrition support. In L. Mahan and
S.Escott Stump (Eds.), Krauses Food and Nutrition Therapy. St. Louis, MO: Saunders, 506528.
National Kidney Foundation/KDOQI. 2000. Clinical Practice Guidelines for Nutrition in Chronic Renal
Failure. Available at: http://www.kidney.org/professionals/KDOQI/guidelines_updates/doqi_nut.html
Pupim, L., Flakoll, P., Brouillete, J., et al. 2002. Intradialytic parenteral nutrition improves protein and energy
homeostasis in chronic hemodialysis patients. J Clin Invest. 110:483492.
Pupim, L., Flakoll, P., Ikizler, T. 2004. Nutritional supplementations acutely increases albumin fractional
synthetic rate in chronic hemodialysis patients. J Am Soc Nephrol. 15:19201926.
Re/Gen Hp/HC shelf stable. Available at: www.nutra-balance-products.com (accessed January 2011).
Stratton, R.J., Bircher, G., Foque, D., et al. 2005. Multi-nutrient oral supplements and tube feeding in mainte-
nance dialysis: A systematic review and meta-analysis. Am J Kidney Dis. 46:387405.
Wang, A., Sanderson, J., Sea, M., et al. 2003. Important factors other than dialysis adequacy associated with
inadequate dietary protein and energy intakes in patients receiving maintenance peritoneal dialysis. Am
J Clin Nutr. 77:834841.
Wilkens, K. and Juneja, V. 2008. Medical nutrition therapy for renal disorders. In L. Mahan and S. Escott
Stump (Eds.), Krauses Food & Nutrition Therapy, 12th edition. St. Louis, MO: Saunders, 921958.
Wolk, R., Moore, E. and Foulks, C. 2007. Renal disease. In M. Gottschlich (Ed.), The A.S.P.E.N. Nutrition
Support Core Curriculum. Silver Spring, MD: American Society for Parenteral and Enteral Nutrition,
591592.
Wong, P., Smith, P. and Rodgers, D. 2003. The use of intradialytic parenteral nutrition to treat malnutrition:
Acase study. CANNT J. 13:3146.
18 Nutrition in Kidney
Transplantation
Nicole Armellino-Nitti
Loyola University Medical Center
Tamara Karosanidze
University of Virginia Health System
CONTENTS
18.1 Introduction: History and Statistics..................................................................................... 245
18.2 Living Kidney Donation and Donor Assessment................................................................246
18.3 Diseases Leading to Stage 5 CKD Requiring Transplantation...........................................246
18.4 Kidney Transplant Evaluation Process................................................................................248
18.5 Nutrition Assessment: Pretransplant................................................................................... 249
18.6 Nutrition Assessment: Posttransplant.................................................................................. 250
18.6.1 Short-Term Nutrition Goals..................................................................................... 250
18.6.1.1 Nutrient and Energy Requirements.......................................................... 251
18.6.1.2 Nutrition-Related Complications.............................................................. 251
18.6.2 Long-Term Nutrition Goals, Nutrition-Related Complications and
Management............................................................................................................ 253
18.6.2.1 Posttransplant Weight Gain...................................................................... 253
18.6.2.2 Posttransplant Diabetes............................................................................. 253
18.6.2.3 HTN, Dyslipidemia, and CVD................................................................. 253
18.6.2.4 Bone Mineral Density............................................................................... 253
18.6.2.5 Infection and Malignancy......................................................................... 254
18.7 Antirejection MedicationsUses, Nutrition-Related Side Effects, and Nutritional
Management........................................................................................................................ 254
18.8 Food Safety and Sanitation.................................................................................................. 255
18.8.1 Simple Rule of Thumb: When in Doubt Throw It Out............................................ 255
18.9 Dietary Supplements............................................................................................................ 256
18.10 PA Guidelines, Restrictions, and Recommendations.......................................................... 258
References....................................................................................................................................... 259
245
246 Nutrition Therapy for Chronic Kidney Disease
the Peter Bent Brigham Hospital in Boston, where a surgical team led by Dr. Joseph Murray trans-
planted a kidney from a healthy male donor into his identical twin brother. The transplant was
successful secondary to the genetic matching of donor and recipient without the aid of iatrogenic
immune-suppression. However, advances in immune-suppressive therapy would be needed to make
transplantation of solid organs between genetically diverse humans a routine and reliable practice
(Linden, 2009).
In 2009 more than 16,000 renal transplants were performed in the United States. Presently, more
than 86,000 individuals are waiting to receive a kidney (OPTN, 2010).
TABLE 18.1
Indications for Renal Transplant
Diagnosis Categories Kidney Diseases
Glomerular diseases Anti-glomerular basement membrane antibody disease (GMB), chronic
glomerulonephritis or glomerulosclerosis, focal segmental
glomerulosclerosis (FSGS), membrane nephropathy, hemolytic uremic
syndrome, Alports syndrome, amyloidosis, Henoch-Schoenlein purpura,
sickle cell anemia
Diabetes Type 1 or type 2
Cystic diseases Polycystic kidneys, medullary cystic kidneys, acquired cystic disease
Hypertensive nephrosclerosis Hypertensive nephrosclerosis
Renovascular and other vascular diseases Chronic nephrosclerosis, malignant hypertension, polyarteritis, progressive
systemic sclerosis, renal artery thrombosis, scleroderma
Autoimmune IgA nephropathy, Goodpastures disease, Wegeners disease, systemic lupus
erythematosis
Nephrotoxic agents Cyclosporine, gentamicin, nonsteroidal anti-inflammatory agents,
analgesics, intravenous contrast dyes, antibiotic, cancer chemotherapy,
radiation, heroin
Congenital, rare familial, and metabolic Congenital obstructive uropathy, cystinosis, Fabrys disease, hypoplasia/
disorders dysplasia/aplasia/dysgenesis/agenesis; nephrophthisis; prune belly syndrome
Tubular and interstitial diseases, urinary Acquired obstructive or analgesic or pyelonephritis/reflux, oxalate
tract abnormalities nephropathy, gout, nephritis, nephrolithiasis, acute tubular necrosis,
cortical necrosis, sarcoidosis, urolithiasis, posterior ureteral valves,
neurogenic bladder, Fanconis syndrome
Neoplasms Incidental carcinoma, lymphoma, myeloma, renal cell carcinoma, Wilms
tumor
Re-transplant/Graft failure Retransplant/graft failure
Other Rheumatoid arthritis, familial nephropathy, nephrotic syndrome, human
immunodeficiency virus (HIV) nephropathy
Cysts
Ureter
Polycystic kidney
FIGURE 18.1 Polycystic kidney. (Courtesy of the National Institute of Diabetes and Digestive and Kidney
Diseases, National Institutes of Health.)
248 Nutrition Therapy for Chronic Kidney Disease
assessment and diets for both the pre- and posttransplant periods are discussed in greater detail later
in the chapter.
When a donor (deceased or living) becomes available, the organ and tissue must be matched by
tissue typing, cross-matching, and antibody screening. Tissue typing is used to determine tissue
compatibility between the donor and candidate. Cross-matching is a blood test to determine how the
recipient will react to the donor. A positive cross-match means the organ is incompatible, whereas
a negative cross-match means the organ is compatible. Antibody screening is used to determine
if the transplant candidate has antibodies that would react to the donors antigens. When a kidney
from a deceased donor becomes available, it is offered to the first person on the transplant list. The
transplant, however, cannot take place if the recipient is not healthy enough to undergo an immedi-
ate major surgery. Factors affecting the final decision for a transplant include tissue match, blood
type, length of time on the waiting list, immune status, and the distance between the donor and the
recipient.
It is also important to note contraindications to kidney transplantation. If a patient has reversible
kidney disease, active infection or chronic untreated infection, untreatable end-stage diseases of
other organs or a limited life expectancy as defined by the transplant center, transplantation may not
be appropriate. In terms of age, chronological age itself is not a contraindication as much as physi-
ological age. Medical issues to consider are advanced extra-renal diseases such as peripheral vas-
cular disease or advanced coronary artery disease as well as improving glycemic control in patients
with diabetes. Medication compliance, substance abuse, and uncontrolled psychiatric disorders also
need to be addressed. If a patient is rejected for transplantation based on medical or psychosocial
findings, he or she may be referred to different transplant centers for another evaluation or may even
be reevaluated at a later time if there are altered circumstances.
The dietitian will then determine the most appropriate diet, making recommendations for calo-
ries, protein, and fluid. Calorie recommendations depend on a patients need to maintain, gain, or
lose weight. Typically, energy needs for pediatric CKD patients are similar to those of healthy chil-
dren of the same age and activity level and are adjusted for height and weight. Energy needs remain
the same for pediatric patients on hemodialysis but are decreased for children on peritoneal dialysis
because of the absorption of dextrose from the dialysate (National Kidney Foundation, 2009). Adult
patients require 2035 cal/kg of body weight but need to be adjusted according to weight status
(Brown et al., 2010). The European Society for Clinical Nutrition and Metabolism recommends
providing at least 3035 cal/kg of body weight per day for stable adult CKD patients on hemodi-
alysis (Cano et al., 2009). The reason for an increase in calories is the catabolic state in patients
with CKD. Protein needs will vary depending on the patients need for dialysis. Recommendations
for children on hemodialysis are the dietary reference intake (DRI) plus 0.1 g/kg body weight per
day and between 0.15 and 0.3 g/kg body weight plus DRI per day for peritoneal dialysis (National
Kidney Foundation, 2009). The ultimate goal for children with CKD is normal growth and devel-
opment, bone development, and metabolic homeostasis. A protein restriction of 0.60.8 g protein
per kilogram of body weight per day in the adult patient may be warranted if the patient has renal
insufficiency or failure but is not on dialysis (Beto and Bansal, 2004). The protein recommenda-
tion for stable patients on maintenance hemodialysis is 1.2 g protein per kilogram of body weight
per day and 1.3 g of protein per kilogram body weight per day for those on continuous ambulatory
peritoneal dialysis (Cano et al., 2006; Kopple, 2001). The increase in protein is needed to replace
albumin and amino acids lost during the dialysis treatment. Together the increase in calories and
protein protect against the protein-calorie malnutrition that may occur when inadequate calories
and/or protein are available to spare protein use as energy. Fluid parameters depend on the severity
and treatment of CKD. In the early stages of kidney disease, there is usually no fluid restriction with
normal urine output (Beto and Bansal, 2004). Adult patients receiving hemodialysis may consume
1000 mL of fluid plus any additional amount equal to urine output; patients on peritoneal dialysis
may consume 15002000 mL of fluid daily (Beto and Bansal, 2004). Typically, the patient will need
to follow a 2 g sodium, 2 g potassium, and 2 g phosphorus diet, but this may be adjusted depending
on serum laboratory values.
The dietitian will also need to assess diet compliance. The patient is expected to follow the
appropriate diet as instructed by the dietitian but may have some difficulties along the way. The
dietitian will troubleshoot and provide additional resources as needed. It is important for the patient
to communicate any questions or concerns to the dietitian regarding the diet (Figure 18.2).
Diseased kidneys
Transplanted
kidney
Artery
Vein
Bladder
Transplanted
ureter
FIGURE 18.2 Transplanted kidney. (Courtesy of the National Institute of Diabetes and Digestive and
Kidney Diseases, National Institutes of Health.)
TABLE 18.2
Calorie Requirements of Pediatric Renal
Transplant Recipients
Age Calorie Requirements (kg)
Infants (01 years)
06 months 108
7 months1 year 98
Toddlers (13 years) 102
Children (410 years)
46 90
710 70
Adolescents (1118 years)
Girls 1114 47
Girls 1518 40
Boys 1114 55
Boys 1518 45
Fat restriction is not recommended during the acute posttransplant phase in adult or pediat-
ric patients. However, dyslipidemia resulting from long-term use of antirejection medications does
warrant following a heart-healthy diet during the chronic posttransplant period (Connolly, 2002;
Kent, 2008).
Fluid and electrolyte requirements during the acute posttransplant phase will vary from patient
to patient and should be individualized based on patients clinical condition. Usually, sodium is not
restricted in patients during the acute posttransplant phase unless there is evidence of poor allograft
function or exacerbation of HTN. In this case, a 2 g sodium diet is recommended (Kent, 2008).
Antirejection medications can cause changes in serum potassium, phosphorus, and/or magne-
sium levels. Patients are closely monitored and recommendations for supplementation are based on
laboratory results.
Mild hyperkalemia is commonly seen in RTRs. Dietary potassium restriction (2 g/day) is often
necessary for potassium levels above 5 mmol/L. Hyperkalemia often occurs when high-dose calci-
neurin inhibitors administered in the acute post-operative phase. Other medications, such as angio-
tensin-converting enzyme inhibitors, angiotensin receptor blockers, and beta blockers may also
exacerbate hyperkalemia when given concurrently. Depending on the severity of hyperkalemia,
in addition to dietary restriction, administration of diuretics, potassium exchange resin (sodium
polystyrene or kayexalate), and/or insulin with glucose and calcium gluconate may be necessary.
Hypokalemia is more common with the administration of sirolimus in kidney transplant patients in
which case a potassium supplementation is needed (Pham et al., 2010).
Hypophosphatemia is another common laboratory abnormality following successful kidney
transplantation. The causes of low phosphorus levels are many and include considerable initial
diuresis (most commonly seen in living-donor kidney transplant recipients), magnesium depletion,
glucosuria, corticosteroid use, and a faulty renal phosphate reabsorption caused by allograft injury.
Rhabdomyolysis, left ventricular dysfunction, insulin resistance, and osteomalacia are just a few
of the negative consequences of severe hypophosphatemia. Mild hypophosphatemia (phosphorus
> 2 mg/dL) may be treated with increased dietary phosphorus intake, whereas a more severe hypo-
phosphatemia (phosphorus < 2 mg/dL) may require administration of oral phosphorus tablets or an
intravenous supplementation (Pham et al., 2010; Teplan et al., 2009).
Hypomagnesemia following renal transplantation is quite common and is brought on by the loss
of magnesium through urine while on cyclosporine or tacrolimus therapy. Patients with diabetes
and those on loop diuretics may also be more prone to having low magnesium levels. Since patients
Nutrition in Kidney Transplantation 253
may have inadequate dietary intake of magnesium, oral supplementation is usually warranted. Oral
magnesium supplements (400800 mg magnesium oxide three times a day) are provided, but intra-
venous magnesium supplementation is necessary in severe hypomagnesemia (<1 mg/dL) (Pham
etal., 2010).
TABLE 18.3
Therapeutic Lifestyle Changes for Adult Kidney Transplant Recipients
Modification Needed Goal
Reducing fat Total fat: 25%35% of total calories
Saturated fat: <7% of total calories
Polyunsaturated fat: up to 10% of total calories
Monounsaturated fat: up to 20% of total calories
Cholesterol <200 mg/day
Carbohydrate 50%60% of total calories; improve glycemic control
Fiber 2030 g/day of which 510 g soluble fiber per day
Plant stanols/sterols 2 g/day
Calories Match intake to output of energy, attain or maintain standard body weight
Waist circumference Men: <40 in. (102 cm)
Women: <35 in. (88 cm)
Waist to hip ratio Men: <1.0
Women: <0.8
Physical activity 2030 min periods of activity 34 times per week of planned moderate
physical activity including a 5 min warm up and cool down resistance
exercise training
Habits Smoking cessation
Alcohol: limit one drink per day with approval of physician
18.7 A
NTIREJECTION MEDICATIONSUSES, NUTRITION-RELATED
SIDE EFFECTS, AND NUTRITIONAL MANAGEMENT
Immunosuppressive medications reduce the incidence and severity of acute rejection considerably,
thus improving patient and graft survival. Patients are prescribed immunosuppressive medications
immediately following the transplant. Patients may also require induction therapy which generally
describes monoclonal or polyclonal antibodies administered via the parenteral route for a short
course during transplantation or immediately posttransplant, which is used to prevent or delay acute
rejection. Induction therapy is also used to provide immunosuppression, which permits immedi-
ate and permanent elimination of one or more of the maintenance medications required after the
transplant. It also has an effect of inducing the hosts immunological tolerance to the alloantigen.
All patients are prescribed maintenance immunosuppressive agents for the life of the transplanted
organ and usually include a multimedication regime consisting of corticosteroids, calcineurin inhib-
itors, antiproliferative agents, and/or mammalian target of rapamycin (mTOR) inhibitors.
Corticosteroids (prednisone, prednisolone, methylprednisone, Solu-Medrol, and Solu-Cortef)
are believed to impede the cell cycle of T and B cells by inhibiting cytokine gene transcription and
secretion (Czock et al., 2005). They also suppress the production of inflammatory mediators by
suppressing prostaglandin synthesis (Granger et al., 2004). Nutrition-related side effects of corti-
costeroids include hyperglycemia and/or the development of diabetes, hyperphagia, osteoporosis,
Nutrition in Kidney Transplantation 255
HTN, hyperlipidemia, protein catabolism, peptic ulcer disease, fluid retention, and electrolyte dis-
turbances, including hypokalemia and hyponatremia. Corticosteroids may impair wound healing
and can increase the risk of infection. Monitoring of blood glucose levels is imperative as well as
possibly following a diabetic diet in the event of persistent hyperglycemia. The patient may also be
advised to follow a low-sodium diet and maintain a healthy weight, which may include losing weight
after graft function has been declared. The patient must consume adequate protein as determined by
a registered dietitian, as well as calcium and vitamin D.
Calcineurin inhibitors (cyclosporine, Neoral, Novartis Pharmaceuticals East Hanover, NJ;
Sandimmune, Novartis Pharmaceuticals, Gengraf, Abbott, Abbott Park, IL; and tacrolimus,
Prograf/FK506, AstellasPharmaUS, Deerfield, IL) limit the lymphocyte proliferation by binding
to their respective intracellular binding proteins thus inhibiting phosphatase activity of calcineurin
and decrease interleukin-2 transcription (Granger et al., 2004; Lin and Cosgrove, 2006). Nutrition-
related concerns are hyperkalemia, hyperglycemia, HTN, hyperlipidemia, hypomagnesemia, hypo-
phosphatemia, and abdominal distress including nausea, vomiting, and diarrhea. The patient may
need to follow a low-potassium, low-sodium, low-fat and/or low-carbohydrate diet, and may need
magnesium supplementation. The patient may need an antiemetic agent to prevent nausea and/or
vomiting.
Antiproliferative agents (azathioprine, Imuran, Prometheus Laboratories, San Diego, CA; myco-
phenolatemofetil, CellCept, Roche Laboratories, Nutley, NJ; mycophenolate sodium, Myfortic;
Novartis Pharmaceuticals, Inc.) also referred to as antimetabolites, suppress the expression of the
immune response by inhibiting the proliferation of lymphocytes after they encounter the antigen
(Granger et al., 2004). They can cause nausea, vomiting, diarrhea, sore throat, and altered taste
acuity. Nutrition therapy includes antiemetic agents as needed and adequate fluid intake to replace
losses.
The medication class of mTOR inhibitors (sirolimus, Rapamycin/Rapamune, Wyeth
Pharmaceuticals, Madison, NJ) prevents the regulatory kinase enzyme in the process of cell divi-
sion (Granger et al., 2004). It is used as part of a maintenance regime and can cause hypertriglyc-
eridemia, hypercholesterolemia, HTN, thrombocytopenia, anemia, diarrhea, acne, rashes, mouth
sores, and delayed wound healing. The patient may need to follow a low-fat and low-sodium diet
and maintain a healthy weight.
going onto the next food, especially if it is a raw or uncooked protein. One must be mindful of cross
contamination that can occur when bacteria spread from one food product to another, especially
with raw meat, seafood, poultry, eggs, and milk.
Foods should be cooked and chilled to the proper temperatures to ensure food safety. A food
thermometer should be used to determine proper cooking temperatures. Beef and egg dishes should
be cooked throughout or to 160F. Poultry and ham should be cooked to a temperature of 165F is
reached. Seafood should be cooked to 145F; shrimp, lobster, and crab should be cooked until they
turn red and the flesh is opaque; clams, mussels, and oysters should be cooked until the shells open.
If the shells do not open, they should be discarded. Foods not consumed at a particular meal should
be chilled within 2 h of cooking as a means to reduce the risk of bacterial growth. The refrigerator
temperature should be kept at 39F or below, and the freezer temperature should be kept at 0F or
below.
Foodborne illness unfortunately resembles symptoms of the influenza virus and can sometimes
be mistaken for it. The symptoms include nausea, vomiting, diarrhea, fever, chills, and sweating. All
transplant recipients on immunosuppressive medications are at an increased risk for severe infec-
tion. If there is suspicion of foodborne illness (or the influenza virus), the patient should contact
his/her physician or heath care provider immediately. The food thought to be the culprit of causing
a foodborne illness should also be preserved in an airtight bag or plastic container and stored in the
freezer clearly marked. The packaging material should also be preserved and should include infor-
mation about the food or beverage item, the date and time it was consumed, and when the symptoms
occurred. One should contact the local health department if the food was from a restaurant of other
food establishment.
of subjects took dietary supplements and that supplement users were more concerned about their
health than nonusers. Study subjects took 15 or more supplements per day, and dietary supplement
was defined as any product containing vitamins, minerals, herbals/botanicals, amino acids, metab-
olites, and extracts. Another study with a slightly larger sample size of 164 patients was conducted
in Germany by Nowack et al. (2009) and described the use of complementary and alternative medi-
cine (CAM) in renal patients treated with dialysis or kidney transplantation. Popularity of CAM in
this population was high with 57% of dialysis patients and 49% of transplant patients taking CAM.
Transplant patients consumed anywhere from 2 to 12 different CAMs. Study researchers identified
41 different types of CAM products used by patients, of which 22% were not safe for renal patients.
Some of these unsafe CAM products included chamomile tea, fruit teas (unspecified), grapefruit
juice, vitamins A and E, and St. Johns Wort (SJW). These products are thought to either accumulate
in renal patients or cause supplementmedication interactions (Nowack et al., 2009).
While patients may report the use of vitamin and mineral supplements to their medical doctor,
the use of herbal products and botanicals is often undisclosed. There may be several reasons for not
admitting to using herbals. Patients may believe that herbals are safe because they are natural and
thus may not consider them a medication. Patients may fail to report the use of herbal products and
botanicals for fear of being discouraged from taking them. Unlike over-the-counter and prescription
drugs, dietary supplements are not regulated by the Food and Drug Administration. The content
and purity of dietary supplements are questionable. They may be contaminated with heavy met-
als (mercury, lead, arsenic, pesticides) or even certain prescription drugs (steroids, diuretics, anti-
inflammatory drugs) making them dangerous to patients with multiple medical conditions who take
myriad medications (Allen and Bell, 2002; Foote and Cohen, 1998). Data are lacking on the safety
of herbal supplements because little is known about the excretion of botanicals and the ability of the
active compounds of herbals to be dialyzed. Cooke et al. (2004) identified popular herbal supple-
ments that may be damaging to the kidneys and are not recommended for use by CKD patients.
Selected herbals and renal concerns are listed in Table 18.4.
The use of herbals and botanicals is not recommended in immunosuppressed patients. There
have been several case reports confirming episodes of acute rejection in patients taking a popu-
lar dietary supplement, SJW. Therapeutic levels of calcineurin inhibitors are significantly lowered
TABLE 18.4
Selected Herbal Supplements Not Recommended for CKD/Kidney Transplant Patients
Herbal Supplement Effects on the Kidney/Possible Interactions
Rhubarb High oxalate content of rhubarb may damage the kidneys if used chronically
Juniper berries This plant can irritate the renal epithelial tissue and increase diuresis
Laxatives such as aloe, senna, cascara These plants may cause electrolyte imbalance
Echinacea May interact with antirejection medications
Evening primrose oil May increase bleeding time
Licorice May cause hypokalemia, hypocalcemia, hyperphosphatemia; may cause
sodium and fluid retention and raise blood pressure
Noni juice Causes hyperkalemia
Saw Palmetto May cause hypertension, urine retention
Stevia May cause hypoglycemia; nephrotoxic in animals
Spirulina (blue-green algae) May increase serum calcium, serum alkaline phosphatase. This supplement
is rich in iron, vitamin A, and mercurymay cause potential vitamin and
metal toxicity
Milk thistle May increase phosphorus absorption
Ginseng (Panax) Increases blood pressure, anxiety. Causes hypoglycemia, insomnia, and
headaches
258 Nutrition Therapy for Chronic Kidney Disease
when SJW is used concurrently with antirejection medications (Allen and Bell, 2002). Barone et al.
(2001) described two cases of RTRs who self-medicated with SJW and developed acute graft rejec-
tion because of low cyclosporine (CSA) levels. CSA and SJW compete for absorption by using the
same mechanisms (P-450 3A4 and/or P-glycoprotein) for metabolism (Radler, 2008). After stopping
SJW, both patients CSA concentrations returned to therapeutic levels. Kidney transplant patients
are often prescribed anticoagulants and aspirin; if common herbals such as garlic, ginkgo, and gin-
seng are taken concomitantly, increased bleeding may occur (Barone et al., 2001). Cardiovascular
problems with the use of Ma huang (ephedra) and hypoglycemic episodes with the use of ginseng
have also been documented (Allen and Bell, 2002).
Healthcare providers are urged to obtain a detailed history of dietary supplement use from their
patients. Ideally, the patient should be asked to bring all of his or her prescribed medications, over-
the-counter drugs, and other supplements to the doctor for review (Allen and Bell, 2002).
significantly less time exercising compared to their healthy counterparts (p = 0.005). Similarly,
the HRQOL scores were lower in transplant patients than in control subjects (p = 0.001), but inter-
estingly, higher HRQOL scores were associated with a higher level of PA in both groups. This
validates the need for emphasizing and promoting regular PA for children following renal transplan-
tation (Hamiwka etal., 2009).
Another study of pediatric RTRs by Sethna et al. evaluated aerobic capacity measured by VO2max
and compared it to healthy children. Researchers reported 13% lower VO2max in transplant patients
compared to their healthy counterparts. Lower hemoglobin levels and use of sirolimus in kidney
transplant subjects were found to be risk factors for lower VO2max (Sethna et al., 2009).
Development of exercise regimens specifically tailored to an individual patient based on clini-
cal status and exercise capacity is urgently needed. Healthcare professionals are urged to counsel
transplant recipients on health benefits of regular PA and refer them to exercise facilities and physi-
cal therapists. Counseling patients on PA should become a routine part of transplant recipients care
(Gordon et al., 2005).
Although no standardized guidelines exist for exercise, the majority of transplant programs
around the world recommend that patients engage in at least 1530 min of PA on most days of the
week. Aerobic exercises (walking, hiking, jogging, running, gardening, dancing, bicycling, swim-
ming), strength and resistance training (lifting weights, riding a stationary bike), and stretching
exercises (yoga, pilates) are encouraged (ITNS, 2010). Generally, transplant recipients are asked to
refrain from heavy lifting and such activities as shoveling, mowing, and raking for 46 weeks fol-
lowing surgery (Cleveland Clinic, 2010; Gheith et al., 2008). The best time to begin an exercise pro-
gram posttransplant is determined by the transplant team and is dependent on a patients recovery
(ITNS.org).
REFERENCES
Allen, D. and Bell, J. 2002. Herbal medicine and the transplant patient. Nephrol Nurs J 29(3):269274.
Barone, G., Gurley, B., Ketel, B., et al. 2001. Herbal supplements: A potential for drug interactions in transplant
recipients. Transplantation 71:239241.
Beto, J. and Bansal, V. 2004. Medical nutrition therapy in chronic kidney failure: Integrating clinical practice
guidelines. J Am Dietetic Assoc 104:404409.
Bia, M., Adey, D., Bloom, R., et al. 2010. KDOQI US Commentary on the 2009 KDIGO practice guideline for
the care of kidney transplant recipients. Am J Kidney Dis 56:189218.
Blue, L. 1992. Nutrition considerations in kidney transplantation. Top Clin Nutr 7(3):1723.
Blue, L. 2002. Adult kidney transplantation. In J. M. Hasse and L. S. Blue eds., Comprehensive Guide to
Transplant Nutrition. Chicago, IL: American Dietetic Association, 4457.
Brown, R., Compher, C., and the American Society for Parenteral and Enteral Nutrition (A.S.P.E.N.) Board of
Directors. 2010. A.S.P.E.N. clinical guidelines: Adult renal failure. J Parenter Enteral Nutr 34:366377.
Buchholz, P. 2006. Renal vitamins. J Renal Nutr 16(2):e1e6.
Cano, N., Aparicio, M., Brunori, G, et al. 2009. E.S.P.E.N. guidelines on parenteral nutrition: Adult renal fail-
ure. Clin Nutr 28:401414.
Cano, N., Fiaccadori, E., Tesinsky, P., et al. 2006. E.S.P.E.N. guidelines on enteral nutrition: Adult renal failure.
Clin Nutr 25:295310.
CDC. Centers for Disease Control and Prevention. 2010. Available at:http://cdc.gov/ (accessed September 9,
2010).
Cleveland Clinic. Exercise guidelines after kidney transplant. Available at: http://my.clevelandclinic.org
(accessed July 12, 2010).
Connolly, C. 2002. Pediatric kidney transplantation. In J. M. Hasse and L. S. Blue eds., Comprehensive Guide
to Transplant Nutrition. Chicago, IL: American Dietetic Association, 172181.
Cooke, J. 2004. Practical aspects of herbal supplement use in chronic kidney disease. J Renal Nutr 14(1):e1e4.
Cupples, S. and Ohler, L. 2003. Solid Organ Transplantation. New York: Springer.
Czock, D., Keller, F., Rasche, F., et al. 2005. Pharmacokinetics and pharmacodynamics of systemically admin-
istered glucocorticoids. Clin Pharmacokinet. 44:6198.
Don, T., Friedlander, S., and Wong, W. 2010. Dietary intakes and biochemical status of B vitamins in a group
of children receiving dialysis. J Renal Nutr 20(1):2328.
260 Nutrition Therapy for Chronic Kidney Disease
Foote, J. and Cohen, B. 1998. Medicinal herb use and the renal patient. J Renal Nutr 8(1):4042.
Gheith, O., El-Saadany, S., Donia, S., et al. 2008. Compliance with recommended life style behaviors in kidney
transplant recipients: Does it matter in living donor kidney transplant? Iranian J Kidney Dis 2(4):218226.
Gordon, E., Prohaska, T., Siminoff, L., et al. 2005. Needed: Tailored exercise regimens for kidney transplant
recipients. Am J Kidney Dis 45(4):769774.
Gourishanka, S., Jhangri, G., Tonelli, M., et al. 2004. Development of diabetes mellitus following kidney trans-
plantation: A Canadian experience. Am J Transplant 4:18761882.
Granger, D., Domenick, M., and Ildstad, S. 2004. Transplantation immunology and immunosuppression. In
C. M. Townsend, R. Beauchamp, B. Evers, and K. Mattox, eds., Sabiston Textbook of Surgery: The
Biological Basis of Modern Surgical Practice, 17th edition. Philadelphia, PA: Saunder, 665697.
Hamiwka, L., Cantell, M., Crawford, S., et al. 2009. Physical activity and health related quality of life in chil-
dren following kidney transplantation. Pediatr Transplant 13:861867.
International Transplant Nurses Society (ITNS). What You Should Know: Diet and Exercise after Transplant.
Available at: http://www.itns.org (accessed July 12, 2010).
Kasiske, B., Cosio, F., Beto, J., et al. 2004. Clinical practice guidelines for managing dyslipidemias in kidney
transplant patients: A report from the managing dyslipidemias in chronic kidney disease work group of
the national kidney foundation kidney disease outcomes quality initiative. Am J Transplant 4 (Suppl.
7):1353.
Kent, P. 2007. Issues of obesity in kidney transplant. J Renal Nutr 17:107113.
Kent, P. 2008. Transplantation. In L. Byham-Gray, J. Burrowes, and G. Chertow, eds., Nutrition and Health:
Nutrition in Kidney Disease. Totowa, NJ: Humana Press, 263286.
Kopple, J. 2001. The National Kidney Foundation K/DOQI clinical practice guidelines for dietary protein
intake for chronic dialysis patients. Am J Kidney Dis 38:S68S73.
Kovac, D., Lindic, J., Kandus, A., et al. 2001. Bone mineral density in kidney transplant recipients. Transplant
Proc 33:36683669.
Lentine, K., Rocca Rey, L., and Bacchi, G., et al. 2008. Obesity and cardiac risk after kidney transplantation:
Experience at one center and comprehensive literature review. Transplantation 86:303312.
Lin, S. and Cosgrove, C. 2006. Perioperative management of immunosuppression. Surg Clin N Am
86:11671183.
Linden, P. 2009. History of solid organ transplantation and organ donation. Crit Care Clin 25:165184.
Martins, C., Pecoits-Filho, R., and Riella, M. 2004. Nutrition for the post-renal transplant recipients. Transplant
Proc 36:16501654.
Meier-Krieshe, H., Vaghela, M. and Thambuganipalle, R., et al. 1999. The effect of body mass index on long
term renal allograft survival. Transplantation 68:12941297.
National Kidney Foundation. 2009. KDOQI (Kidney Dialysis Outcomes Quality Initiate) Clinical practice
guideline for nutrition in children with CKD: 2008 Update. Am J Kidney Dis 52:S1S124.
Nowack, R., Ball, C., Birnkammer, F., et al. 2009. Complementary and alternative medications consumed by
renal patients in southern Germany. J Renal Nutr 19(3):211219.
Orazio, L., Hickman, I., Armstrong, K., et al. 2009. Higher levels of physical activity are associated with a
lower risk of abnormal glucose tolerance in renal transplant recipients. J Renal Nutr 19(4):304313.
Organ Procurement and Transplantation Network (OPTN). 2010. Available at: http://optn.transplant.hrsa.gov
(accessed July 12, 2010).
Painter, P., Hector, L., Ray, K., et al. 2002.A randomized trial of exercise training after renal transplantation.
Transplantation 74:4248.
Pham, P-T., Pham, P-C., and Danovitch, M. 2010. The acute care of the transplant recipient. In D. McKay
and S. Steinberg, eds., Kidney Transplantation: A Guide to the Care of Kidney Transplant Recipients.
Springer Science + Business Media, LLC, 207235.
Radler, D. 2008. Dietary supplements. In L. Byham-Gray, J. Burrowes, and G. Chertow, eds., Nutrition and
Health: Nutrition in Kidney Disease. Totowa, NJ: Humana Press, 531541.
Roberts, D., Dive, C., and Renehan, A. 2010. Biological mechanisms linking obesity and cancer risk: New
perspectives. Ann Rev Med 61:301316.
Sethna, C., Salerno, A., McBride, M., et al. 2009. Cardiorespiratory fitness in pediatric renal transplant recipi-
ents. Transplantation 88:395401.
Singh, D., Lawen, J., and Alkhadair, W. 2005. Does pretransplant obesity affect the outcome in kidney trans-
plant recipients? Transplantation Proc 37:717720.
Spanner, E. and Duncan, A. 2005. Prevalence of dietary supplement use in adults with chronic renal insuf-
ficiency. J Renal Nutr 15(2):204210.
Nutrition in Kidney Transplantation 261
St. Lukes Episcopal Hospital. Texas Medical Center. 2009. A Guide to Living Kidney Donation. Available at:
www.stlukeshouston.com (accessed July 12, 2010).
Teplan, V., Valkovsky, I., Teplan, Jr., V., et al. 2009 Nutritional consequences of renal transplantation. J Renal
Nutr 19(1):95100.
USRDS. 2010. United States Renal Data System. Available at: http://www.usrds.org/ (accessed September 9,
2010).
Zelle, D., Corpeleijin, E., van Ree, R., et al. 2010. Markers of the hepatic component of the metabolic syndrome
as predictors of mortality in renal transplant recipients. Am J Transplant 10:106114.
19 Establishing Quality
Improvement Parameters
Lynn K. Thomas
University of South Carolina School of Medicine
CONTENTS
19.1 Introduction.......................................................................................................................... 263
19.2 Evidence-Based Practice......................................................................................................264
19.3 Quality Improvement............................................................................................................ 265
19.4 Development of Protocols.................................................................................................... 272
19.4.1 Resistance to Change................................................................................................ 273
19.5 Stages of CKD...................................................................................................................... 273
19.6 Clinical Practice Guidelines for Stage 13 CKD
Patients.................................................................................................................................. 274
19.7 Clinical Practice Guidelines for Stage 4 CKD Patients....................................................... 274
19.8 Clinical Practice Guidelines for Stage 5 CKD Patients....................................................... 275
19.8.1 Frequency and Minimum Criteria for Nutritional Assessments............................... 275
19.8.2 Serum Albumin and Other Measures of Nutritional Status..................................... 275
19.9 Patient-Centered Concepts................................................................................................... 276
19.10 What Does KDIGO Mean?.................................................................................................. 276
19.11 Summary.............................................................................................................................. 277
References....................................................................................................................................... 277
19.1 INTRODUCTION
We know nothing of the principle of health, the positive of which pathology is the negative, except
from observation and experience. And nothing but observation and experience will teach us the ways to
maintain or to bring back the state of health.
(Nightingale, 1860)
Florence Nightingale (Figure 19.1), in mid-nineteenth century, was one of the first health care practi-
tioners to collect and analyze data to be used as the basis for improving patient outcomes. Years later,
Ernest Codman, founder of the American College of Surgeons (ACS), took on the task of recording
outcomes, but in his zeal for documenting end results and for publicly insulting his colleagues,
he was ostracized and forced to resign from the organization he had created (Neuhauser, 2002). In
1917, the ACS finally established a hospital standardization program. The standards focused on care
within hospitals and had clinical review as one of the five minimum standards (Roberts et al., 1987).
Once the minimum standards were in place, the ACS began surveying health care organizations to
determine their suitability to become accredited. After a few years, the minimum standards were
expanded and more rigorous criteria were put in place (Luce et al., 1994). The ACS also united with
the American College of Physicians, the American Hospital Association, the American Medical
Association, and the Canadian Medical Association to form the Joint Commission on Accreditation
of Hospitals Organization (JCAHO). In 1975, the JCAHO expanded to include ambulatory care
263
264 Nutrition Therapy for Chronic Kidney Disease
centers such as outpatient surgery and dialysis clinics. Todays dialysis centers must be certified by
the Centers for Medicare and Medicaid Services (CMS) and receive accreditation through JCAHO
or the Accreditation Association for Ambulatory Health Care.
TABLE 19.1
Evidence-Based Guideline Resources
American Dietetic Association www.adaevidencelibrary.com
Centre for Evidence-Based Medicine www.cebm.net
Clinical Evidence www.clinicalevidence.bmj.com
Cochrane Library www.thecochranelibrary.com
Essential Evidence Plus www.essentialevidenceplus.com
Health Sciences Research www.nlm.nih.gov/hsrinfo/datasites.html
National Guidelines Clearinghouse www.guideline.gov
University of York Centre for Reviews and Dissemination www.crd.york.ac.uk/CMS2web
TABLE 19.2
Total Weighted Performance Score
Hgb < 10 g/dL:50% Use 10 points for each measure
Hgb > 12 g/dL:25% Subtract 2 points for every 1.0% below the performance standard
Urea reduction ratio > 65%:25% Sum to create total performance score
Performance scores are posted at Dialysis Compare Website www.
medicare.gov/dialysis
among specialties; (3) it is a comprehensive evaluation of the overall quality of evidence; (4) it pro-
vides evaluation of important clinical outcomes; (5) it contains a risk benefit analysis; and (6)it is
applicable to a wide range of clinical questions. The National Kidney Foundations Kidney Disease
Outcomes Qualifications Initiative (NKF KDOQI, 2002) guidelines for grading a studys qual-
ity use an ABC approach: A = least bias, B = susceptible to some bias, and C = significant bias.
Guidelines are extremely useful in assisting the decision-making process in specific clinical cir-
cumstances. It offers basic recommendations that are supported by review of the current literature.
Overall, the clinical expertise of the practitioner remains crucial (Roberts and Reed, 2009; Uhlig
etal., 2006). A list of evidence-based guideline resources can be found in Table 19.1.
267
(Continued)
268
TABLE 19.3 (Continued)
Measures Assessment Tool from the Centers for Medicare and Medicaid Services
Tag Condition/Standard Measure Values References Source
V546 (2) Nutritional status (pediatric) monitor Length/height, weight, BMI, nPCR Normalized nPCR for HD teen, nPCR KDOQI Chart
monthly N/A younger Pediatric
Nutrition 2008
V546 (3) Mineral metabolism and renal bone Calcium corrected for albumin (BCG) Normal for lab; preferred upper level KDOQI Bone Chart
disease <10/mg/dL Metabolism
and
Monitor calcium and phosphorus monthly Phosphorus All: 3.55.5 mg/dL Disease 2003
Monitor intact PTH every 3 months Intact PTH Adult: 150300 pg/mL; Pediatric:
200300 pg/mL
V547 (4) AnemiaHgb non-ESAmonitor Hemoglobin (Adult and pediatric) >10.0 g/dL KDOQI Anemia DFR
monthly 2006
V547 (4) AnemiaHgb on ESAmonitor Hemoglobin (Adult and pediatric) <12.0 g/dLa DFR
monthly
V548 Hemoglobin (Adult and pediatric) 1012.0 g/dLb
269
270
TABLE 19.3 (Continued)
Measures Assessment Tool from the Centers for Medicare and Medicaid Services
Tag Condition/Standard Measure Values References Source
V629 (i) PD adequacy (rolling average, each PD: Adult % with weekly Kt/Vurea 1.7 (dialysis Conditions for DFR
patient tested 4 months) + RKF) Coverage
CMS CPM Records
4/1/2008
V630 (ii) Nutritional status Facility set goals; refer to parameters listed in V509 % of patients within target range on Conditions for Records
albumin and other nutritional Coverage
parameters set by the facility
V631 (iii) Mineral metabolism/renal bone disease Calcium, phosphorus, and PTH % in target range monthly Conditions for Records
Coverage
CMS CPM
4/1/2008
V632 (iv) Anemia management Mean hemoglobin (patient with ESRD at 3 months) % with mean 1012 g/dL Conditions for DFR
Coverage
Abbreviations:BP, blood pressure; BCG/BCP, bromcresol green/purple; BMI, body mass index; CAHPS, consumer assessment of healthcare providers and services; CFU, colony-forming
units; CHr, reticulocyte hemoglobin; DOPPS, Dialysis Outcomes and Practice Patterns Study; ESA, erythropoiesis stimulating agent; KDOQI, Kidney Disease Outcomes
Qualifications Initiative; MIPPA, Miedicare Improvements for Patients and Providers Act of 2008; nPCR, normalized protein catabolic rate; PTH, parathyroid hormone; RKF,
residual kidney function; spKt/V = single-pool Kt/V; QoL, quality of life.
Note: DFR = Dialysis Facility Reports; CW = CROWNWeb; Chart = Patient Chart; Records = Facility Records; Interview = Patient/Staff Interview.
a FDA box warning.
b Medicare reimbursement.
e Fistula First.
f KDOQI 2006.
g Fistula First.
271
272 Nutrition Therapy for Chronic Kidney Disease
The newest initiatives involve patients in the development of clinical practice guidelines. Patients
provide feedback on their health care experiences and then collaborate with researchers to define
objectives and indicators (Daz Del Campo et al., 2011).
All patients with inter-dialytic weight gains more than 5% of dry weight will trigger patient counseling.
As a sub-study, try different approaches to patient education. A new idea to consider is cohesive coun-
seling in order to send the same message throughout differing disciplines. Example: If a patient arrives
with excessive fluid gains, the diet technician or nurse should be ask the patient to use a check list to
identify foods and fluids consumed since the last treatment. Once the list is completed, the staff has the
option to refer to the dietitian (if available) or pick from a list of appropriate counseling messages. If the
fluid gains are from too much liquid, then pathway one. If the fluid gains are from too many salty foods,
Protocol development
Do a pilot study
then pathway two. Using this approach eliminates the cut back on all fluids approach. No one wants
to advise limiting the nutritional supplement or a fortified juice, along with the ice chips. Salty snack
foods might be really be the culprit.
Now, assess the effect of the new protocol. Did the number of excessive inter-dialytic weight
gains among the patients improve? Was the staff time adequate to educate the patient? How much
additional training was required? Was the ebb and flow of patient care interrupted by this protocol?
When the new protocol is executed, always add a date for review or renewal. As needed, collect
outcome data to provide justification for new staffing or equipment or materials.
TABLE 19.4
Stages of Chronic Kidney Disease
Stage Glomerular Filtration GFR (mL/min/1.73 m2)
1 Normal ratea 90
2 Mildly deficient 6089
3 Moderately deficient 3059
4 Severely deficient 1529
5 Failure 15 or dialysis
assessment is also recommended quarterly, as are dietary counseling sessions (National Kidney
Foundation, 2000). The subjective global assessment focuses on nutrient intake and body composi-
tion (McCann, 1996). Nutritional status should be assessed more frequently if there is evidence that
there is inadequate food intake, protein-energy malnutrition, or the presence of a comorbidity that
worsens baseline nutrition status.
Quality improvement indicators can be constructed around laboratory reports with the goal of
all values being within expected parameters. Quantitative indicators should be driven by changes
in weight, food intake, gastrointestinal function, activities of daily living, comorbidities, and physi-
cal signs of malnutrition. Measurement of these factors is very important since poor nutritional
status predicts poor outcome and the development of protein-energy malnutrition (National Kidney
Foundation, 2000).
1. Patients have the right of access to a qualified renal dietitian who will provide a compre-
hensive nutrition assessment and counseling for nutritional needs. The dietitian will also
assist with a plan of care and a quality assessment and performance improvement program.
Patients will have the opportunity to participate in their care plan.
2. The renal dietitian will be registered with the American Dietetic Association and have at
least one year of professional work experience as an RD in a clinical setting. The dietitian
will be able to independently perform the duties of nutrition assessment, evaluation of
laboratory values, and provide assistance to an interdisciplinary team in terms of manage-
ment of anemia, bone mineral disorders, and kinetic modeling.
The recommendation to use serum albumin as the sole performance measure comes with cau-
tions. Serum albumin, although recommended by the NKF KDOQI and CMS guidelines, has not
been shown to be a reliable measure of nutrition status (de Mutsert et al., 2009). Levels are extremely
susceptible to different influences such as inflammation, infection, decreased synthesis from liver
disease, acute stress, chronic stress, gastrointestinal loss, tissue injury, and volume overload. Levels
are best interpreted over time by using multiple serum albumin values or by pairing serum albumin
with other markers (Ikizler, 2009). A composite approach more fully reflects the complicated nature
of the complete nutrition assessment. Serum albumin should be partnered with a measurement such
as change in dry weight or nPNA and at least one other reliable indicator of possible malnutrition.
According to NKF KDOQI guideline 4, serum pre-albumin is also a valid and clinically useful
measure of protein and energy malnutrition. Unfortunately, the same limitations apply to its use
as an indicator of malnutrition. The C-reactive protein test can be used in conjunction with serum
albumin to evaluate inflammation as the reason for a subnormal value. A very low serum cholesterol
reading is also an indicator of acute infection or starvation. Markers for iron deficiency, such as total
iron binding capacity (TIBC), transferrin, transferrin saturation, or mean corpuscular volume, can
be used to provide clues to the cause of a low serum albumin. Other tests might include total protein,
lymphocyte count, alpha-1 acid glycoprotein, creatinine, magnesium, zinc, and potassium (National
Kidney Foundation, 2000; Thompson, 2003; Tsirpanlis, 2005). An example of a composite measure
of performance might be to pair serum albumin and serum creatinine since a relationship has been
established by reports in the literature (Segall et al., 2008).
Other measures of nutritional status can be derived from monitoring such items as change in
usual dry weight over time or in the findings from repetitive anthropometric assessment. Significant
variations in weight may be overlooked in the presence of pretreatment fluid gains, so it is impor-
tant to access changes on a monthly basis. Anthropometric assessments should be completed at
least every 6 months. Indicators should address the interventions that are put in place once change
is noted. The effectiveness of the intervention should be compared to baseline. No single indicator
provides a comprehensive assessment of a patients nutritional health.
19.11 SUMMARY
Quality improvement indicators or clinical practice guidelines are important to facilitate the excel-
lence in care that every patient deserves. Clinicians should be careful to find the correct balance of
national and local guidelines. The guidelines should be valid, appropriate, and easily incorporated
into the daily routine. They should be grounded in evidence-based research. A system of indicators/
guidelines reviews should be in place in each clinic and for every area of practice. Implementation
of guidelines requires the input of all practitioners so obstacles can be identified and corrected.
REFERENCES
American Dietetic Association (ADA) Evidence Based Library. 2011. Nutrition Screening. Available at: www.
adaevidencelibrary.com/topic.cfm?cat=3584 (accessed August 2011).
Campos Gutirrez, B., Lou Arnal, L., Gimeno Orna, J., et al. 2011. Undiagnosed kidney disease in hospitalized
patients: An opportunity for improvement. Nefrologia 31(1):7075.
Centers for Medicare and Medicaid Services Conditions for Coverage (CMS). 2008. Available at: http://www.
cms.gov/CFCsAndCoPs/downloads/ESRDfinalrule0415.pdf (accessed April 12, 2011).
Centers for Medicare and Medicaid Services (CMS). (2011) Available at: https://www.cms.gov/ESRDQuality
ImproveInit/downloads/QIPODF09212010.pdf (accessed April 10, 2011).
de Mutsert, R., Grootendorst, D., Indemans, F., et al. 2009. Association between serum albumin and mor-
tality in dialysis patients is partly explained by inflammation, and not by malnutrition. J Renal Nutr.
19(2):127135.
Daz Del Campo, P., Gracia, J., Blasco, J., et al. 2011. A strategy for patient involvement in clinical prac-
tice guidelines: Methodological approaches. BMJ Qual Saf. Published Online First: April 2, 2011. doi:
10.1136/bmjqs.2010.049031
Eknoyan, G. 2010. Why we need clinical practice guidelines in chronic kidney disease. J Renal Nutr.
20(5):S127S130.
Eknoyan, G., Lameire, N., Baroum, R., et al. 2004. The burden of kidney disease: Improving global outcomes.
Kidney Int. 66:13101314.
Fetter, M. 2003. Geriatric assessment and management protocols. J Infusion Nurs. 26:153160.
Fouque, D. and Laville, M. 2009. Low protein diets for chronic kidney disease in non-diabetic adults. Cochrane
Database Syst Rev. 3:CD001892.
Ikizler, T. 2009. Nutritional requirements in hemodialysis patients. In Mitch, W. and Ikizler, T. eds. Handbook
of Nutrition and the Kidney, 6th edition. Philadelphia, PA: Lippincott Williams & Wilkins, 177195.
Jones, N., Suurdt, J., Ouelette-Kuntz, H., et al. 2007. Implementation of the Canadian clinical practice guide-
lines for nutrition support: A multiple case study of barriers and enablers. Nutr Clin Pract. 22:449457.
Kent, P. 2005. Integrating clinical nutrition practice guidelines in chronic kidney disease. Nutr Clin Pract.
20(2):213217.
Knight, E., Stampfer, M., Hankinson, S., et al. 2003. The impact of protein intake on renal function decline in
women with normal renal function or mild renal insufficiency. Ann Intern Med. 138:460467.
Levey, A., Greene, T., Samak, M., et al. 2006. Effect of dietary protein restriction on the progression of kid-
ney disease: Long-term follow-up of the modification of diet in renal disease study. Am J Kidney Dis.
48(6):879888.
Lowrie, E., Huang, W., and Lew N. 1995. Death risk predictors among peritoneal dialysis and hemodialysis
patients. Am J Kidney Dis. 26:220228.
Luce, J., Bindman, A., and Lee, P. 1994. A brief history of health care quality assessment and improvement in
the United States. West J Med. 160(3):263268.
McCann, L. 1996. Subjective global assessment as it pertains to nutrition status. Dialysis Transplant. 25(4):190.
National Kidney Foundation. 1997a. DOQI clinical practice guidelines for hemodialysis and peritoneal ade-
quacy. Am J Kidney Dis. 30:Suppl 3.
National Kidney Foundation. 1997b. DOQI clinical practice guidelines for vascular access. Am J Kidney Dis.
30:S150S191.
National Kidney Foundation. 2000. KDOQI nutrition in chronic renal failure. Am J Kidney Dis. 35(6) Suppl
2:S1S141.
National Kidney Foundation. 2002. KDOQI clinical practice guidelines for chronic kidney disease: evaluation,
classification, and stratification. Available at: www.kidney.org (accessed April 6, 2011).
Neuhauser, D. 2002. Ernest Amory Codman, MD. Qual Saf Health Care. 11(2):104105.
278 Nutrition Therapy for Chronic Kidney Disease
Nightingale, F. 1860. Notes on Nursing. New York: Appleton and Company, 129.
Roberts, J., Coale, J., and Redman, R. 1987. A history of the joint commission on accreditation of hospitals.
JAMA 258:936940.
Roberts, S. 2008. Evidence based protocols: Why protocols are beneficial and considerations for implementa-
tion. Support Line 30(2):2326.
Roberts, S. and Reed, L. 2009. Understanding and applying evidence based guidelines in clinical practice.
Support Line 3192:1621.
Rubin, H., Jenckes, M., Fink, N., et al. 1997. Patients view of dialysis care: Development of a taxonomy and
rating of importance of different aspects of care. CHOICE study. Am J Kidney Dis. 30(6):793801.
Segall, L., Covic, A., Mardare, N., et al. 2008. Nutritional status evaluation in maintenance hemodialysis
patients. Rev Med Chir Soc Med Nat Iasi. 112(2):343350.
Steinwachs, D. and Hughes, R. 2008. Health services research: Scope and significance. In: Hughes, R., ed.,
Patient Safety and Quality: An Evidence-Based Handbook for Nurses. Books and Documents. Available
at: www.ncbi.nlm.nih.gov/pubmed/21328761
Thompson, C. 2003. Laboratory assessment. In Charney, P. and Malone, A., eds., ADA Pocket Guide to Nutrition
Assessment. Chicago, IL: American Dietetic Association, 63141.
Tsirpanlis, G. 2005. The pattern of inflammation and a potential new clinical meaning and usefulness of
C-reactive protein in end-stage renal failure patients. Kidney Blood Press Res. 28(1):5561.
Uhlig, K., MacLeod, A., Craig, J., et al. 2006. Grading evidence and recommendations for clinical practice
guidelines in nephrology. Kidney Int. 70:20582065.
U.S. Department of Agriculture. 2011. Choose my plate. Available at: www.choosemyplate.gov (accessed
August 2011).
Wrone, E., Carnethon, M., Palaniappan, L., et al. 2003. Association of dietary intake and microalbuminuria in
healthy adults: Third national health and nutrition examination survey. Am J Kidney Dis. 41(3):580587.
20 Counseling Strategies
Matthew Orr
University of South Carolina School of Medicine
CONTENTS
20.1 Grabbing the Low-Hanging Fruit: Solution-Focused Interventions
for Brief Counseling.............................................................................................................. 279
20.2 Developing a Solution Focus.................................................................................................280
20.2.1 Solution-Focused Therapy.........................................................................................280
20.2.2 Circular Questions.....................................................................................................280
20.2.3 Tell Me .................................................................................................................. 281
20.3 Techniques............................................................................................................................. 281
20.3.1 Exceptions to the Problem......................................................................................... 281
20.3.2 Compliments.............................................................................................................. 282
20.3.3 Miracle Question....................................................................................................... 283
20.4 One Thing Technique............................................................................................................ 283
20.4.1 One Thing.................................................................................................................. 283
20.4.2 Scaling Questions...................................................................................................... 285
20.4.2.1 Introduction of the Scale............................................................................. 285
20.4.2.2 Following Up and Concretizing Goals and Hypothetical
Solutions...................................................................................................... 285
20.4.3 From Scaling Questions to the One Thing................................................................ 286
20.5 Reframing.............................................................................................................................. 287
20.5.1 Life Lessons: Reframing........................................................................................... 288
20.6 Crystal Ball............................................................................................................................ 289
20.7 Conclusion............................................................................................................................. 289
References....................................................................................................................................... 289
20.1 G
RABBING THE LOW-HANGING FRUIT: SOLUTION-
FOCUSED INTERVENTIONS FOR BRIEF COUNSELING
One of the most challenging tasks for patients with chronic health conditions is to navigate all
the lifestyle modifications their health care providers tell them they must make. Some may argue
that this is never any truer than it is for patients with chronic kidney disease (CKD), who are often
expected to adapt to highly restrictive diets as well as modify other health behaviors, such as physi-
cal activity, smoking cessation, and medication adherence. This chapter provides a practical patient-
centered approach to counseling patients who have difficulty making these changes. Although the
focus of this book is dietetics, most health care providers will no doubt find themselves counseling
patients with CKD on these other health behaviors as well.
279
280 Nutrition Therapy for Chronic Kidney Disease
One, define what the client wants rather than what he or she does not; two, look for what is working
and do more of it; three, if what the client is doing is not working, then have him or her do something
different. (p. 6)
These basic tenets of solution building are embodied in the techniques described in this chapter;
each technique contains some element of both exploring what has gone well in the past and discov-
ering what is going well right now and what the patient thinks will go well in the future. As these
techniques are applied, the conversation between the clinician and the patient becomes less problem
oriented and more solution focused (e.g., taking into account what patient wants vs. what he or she
does not want), and there is a shift of viewpoint from what holds the patient back to what propels
him or her forward. The idea is not to suggest that there is a behavioral intervention that will cure
chronic illness; rather, the idea is to promote methods that empower people to improve their quality
of life and perhaps influence the course of their illness. This approach encourages patients to grab
the low-hanging fruit on the tree, so to speak, rather than to simply diagnose what they are doing
wrong and then construct interventions to correct those deficits. This latter approach is akin to ask-
ing the patient to navigate a winding, obstacle-filled path to the top of the tree, where the fruit is no
healthier or tastier.
its management. For example, instead of the clinician asking the patient, What is difficult about
following the diet? a circular style will sound as follows:
Tell me about a time when you were able to follow one of the food recommendations?
Where were you?
Who was there?
What was going on?
What did you do?
What did (they) do?
What happened next?
And then what happened?
How often does it go this way?
What is different about when it does go this way?
Instead of focusing on why patients have not been able to follow their diets, for example, this
approach aims to help patients discover, in their own words, the specific factors or resources (i.e., peo-
ple, places, actions, and abilities) that have contributed to successful decision making and behavior,
such as following a dietary recommendation in the above example. Each response to a question about
past successes represents another possible solution in the here and now. If a patient identifies that
her last dietary success was that she ordered a salad for lunch, that her best friend was with her and
ordered the same thing, and that she was motivated by knowing that she would be eating an early din-
ner, she has just verbalized several supportive psychosocial factors on which the clinician and patient
can construct future solutions, namely, building in more social supports and modifying her eating
schedule. While this focus on social supports and daily schedules is nothing new to health counsel-
ing, the advantage of SFT methods and using a circular questioning style is that it is the patient who
generates these ideas, and what is more, her responses reveal what has worked for her.
Indeed, questions are key to collecting information and getting to know patients. However, a cir-
cular question in and of itself can serve as a potent intervention technique (McGee et al., 2005). For
example, What has been going well with your food choices? is more effective than asking How
is your diet going? The value of the former question is much more than the difference between
open-ended and closed-ended questions. The value is that the patient has to stop and think about
what specifically has been going well, which raises his or her level of insight into and awareness of
the particular circumstances of the situation and highlights possible solutions.
20.3 TECHNIQUES
20.3.1 Exceptions to the Problem
Central to the concept of constructing solutions is identifying exceptions to the problem (Berg,
1994; de Shazer, 1988). This technique encourages patients to explore the times when they have not
been mired in their current problem. The intent of this intervention is to determine what has worked
282 Nutrition Therapy for Chronic Kidney Disease
in the past for the patient in order to promote doing more of it in the here and now. Consider the
following excerpt from an interview between a clinician and a patient, Sue, whose current distress
is her uncontrolled diabetes and concomitant fatigue and low mood:
Clinician: Tell me about the last time your blood sugar was under control.
Sue: Its been a while since it was really down. Its always so up and down.
Clinician: It sounds like youve been dealing with a lot (expressing empathy). How about just
tell me about the last time you felt better than you do now. (Clarifying and simplifying the
request out of respect for her condition fatigue and possible poor concentration)
Sue: Oh I guess it was a month ago ... . Yeah, it was definitely last month.
Clinician: What was different about last month?
Sue: I was going on my walks, eating pretty good food, and I was spending more time reading
my Bible. I let myself get away from that. Yeah, thats it exactly! My daughter and her kids
moved back in with me and shes had all of this trouble with money and Ive had to help
her carry the kids to school and around town because she works at night. I love them, but
Id just like some time to myself again.
Clinician: My goodness. It sounds like you know how to take care of yourself! How did you
make all of that happen ... the walking and eating and the Bible study?
Sue: Oh, well, I used to be pretty active and fit when I was young, but then had kids and let
myself go. Ive been battling weight problems for about twenty years, and then I found out
I had diabetes. I decided I had to take care of myself and I was doing really well until this
last year and then Ive been up and down ... lots of stress you know?
Clinician: Wow, you are a determined person. You take care of yourself and then you take
care of your daughter and grandkids. ... Youre not going to let anything happen to them it
sounds like. I wonder if it is a matter of finding ways to do both at the same time.
Sue: I think that is very true.
Clinician: Something tells me you will find a way to make it happen. In the meantime, I would
be happy to help you sort out how you might do it when you feel up to it.
20.3.2 Compliments
In the preceding exchange the clinician punctuates Sues comments about her behavior in the past
with compliments. Giving compliments (Berg, 1994; de Shazer, 1988) is another solution-focused
and circular interviewing method that helps bring to light peoples strengths and resources. The
clinician refrains from focusing on why having her daughter and grandchildren living her causes
her stress and how she might cope with it. Instead, the clinician compliments her determination and
her ability to take care of herself and suggests that she had simply transferred that determination
and care from herself to them. This is inherently more empowering than suggesting that she is not
coping well enough.
There is always something for which patients can be complimentedthe fact that they managed
to make it to their appointment that day or that they have made it through adversity to get to their
current point in the life are examples. One can wonder aloud: How did you manage to make that
happen? or Where or from whom did you learn to make it happen? Patients living with chronic
and potentially debilitating illnesses can feel patronized and dismissed if clinicians move directly
Counseling Strategies 283
into teaching cognitive and behavioral coping skills because this sends the message that what they
have been doing is wrong and that they must learn something new in order to succeed. By focusing
on a patients indisputable accomplishments, such as making his or her appointment or keeping his
or her diabetes under control for 6 months prior to a current symptomatic episode, clinicians can
help to establish that the evidence demonstrates that the patient possesses the necessary resources
to succeed in his or her own way.
Suppose this evening you get tired and go to sleep ... , and in the middle of the night, when you are fast
asleep, a miracle happens and something changes that makes things better for you. ... But because you were
asleep you did not know it had happened. ... When you wake up the next morning, what do you notice that
tells you a miracle happened? What has changed/improved? What else do you notice? What else?
This can be highly effective at identifying specific behaviors that are amenable to change; how-
ever, the clinician may need to help move the patient through this exercise. It is common for patients
to respond, I would be rich or I would have a million dollars. A solution-focused response to this
would be, Sounds like that might make a difference. Now lets think about something a bit more
reasonable, something a bit more likely to happen soon. People also often answer this question with
a negative that states the opposite of the problem. For example, I wouldnt have kidney disease or
My husband would listen to me more or My son would stop asking me for money. These are not
issues people can resolve or change overnight because they cannot change the fact that they have
a disease or immediately change another persons behavior. But these wishes are not necessarily
impossible and focusing on them provides an excellent opportunity to highlight the roles people play
in their own frustrations and promotes a sense of control and influence over these problems by ask-
ing: If that happened what would you notice was different about yourself?
This helps people focus on themselves and on the behaviors or characteristics that are more likely
under their immediate control and influence as well as emphasizes beginning with small, manage-
able changes. With just this one question, people often shift from an external focus on what other
people are doing wrong to being quite specific about what they themselves can do to improve their
situation. Clinicians may also hear common responses such as, I would pray first thing when I
woke up or I would get up and make my own breakfast or I would ask my husband to help me
make breakfast.
Such responses indicate that the patients are intentionally thinking about what actions they could
take to improve their situations. The question-response exchange also suggests that the possibil-
ity of change is within the patients reach and that the patient is capable of making these changes.
Therefore, it is not necessary to follow up with a plan to implement these changes; the patients
realization of these possibilities is intervention enough since it is up to each patient to decide how
and when to put them into action. Of course, clinicians may wish to pursue this discussion further.
different about his or her situation and leads the way toward identifying concrete ways to achieve a
goal. It begins:
Tell me just one thing that you would like to see be different about yourself or your situation?
An alternative to this question in situations where there is a premium on decreasing the pressure
the patient is feeling and increasing manageability of the problem, is as follows:
What is one thing that could change or improve about you or your situation that will make it more
likely that will happen?
The idea is to use as many follow-up questions as necessary to peel the layers of the onion and
arrive at a concrete, manageable action the patient can take. The following is an example of such a
conversation between a primary care physician and Linda, a 52-year-old female patient with CKD
who had not experienced many symptoms before a recent bout of persistent fatigue, swollen ankles,
and changes in her urination, which frightened her and led to her lamenting her struggle to stick to
her diet and nutrition plan:
Dr: Tell me just one thing that you would like to see be different about yourself or your
situation?
Linda: If I could stick to the diet plan that would help, of course.
Dr.: What is something that you could do to make this happen?
Linda: It is so hard, this diet is so blah! If there was some way to stick to it I would do it.
Dr: It does sound like a tremendous challenge! What is just one thing that could change or be
different about you or your situation will make it just a little more likely that will happen?
Linda: I dont know ... . I guess it would be being able to fix my own food and not worry
about having to cook or eat with the rest of my family. If I dont to take care of my hus-
band and my son and grandchildren, no one will, and we eat a lot of big family dinners
every week with my sisters and their families and I cook for everyone. I cant expect them
to eat stuff from my boring diet and its hard to turn down that tasty food when its right
there. Yeah, I suppose that would be it ... things would be easier if I only had to cook for
myself.
This exchange could stop here and still be productive since the patient has now acknowledged
a potential solution, and it would be appropriate to emphasize her autonomous decision making by
letting her sit with this thought. However, the physician decides it would be more helpful to peel the
layers of the onion to identify solutions that depend less on the cooperation of others:
Dr.: What would have to happen to make it a little more likely you will cook for yourself?
Linda: (chuckling) Oh, Id have to move out.
Dr.: That doesnt sound like an option at this point, does it? Short of moving out, whats one
thing that will make it a bit easier to get a meal or two to yourself?
Linda: Thats funny, you say a meal or two and Im always thinking that I have to eat right [at]
every meal or whats the use. I can probably shoot for a meal or two each week when its
just me and my husband if you think that might help.
Dr.: It sounds like a great start. When you get to the point where you are ready to make this
adjustment, what do you think it will be that makes it happen the first time?
Linda: I guess it will be that I tell my husband and son that this is something I have to do.
They were pretty concerned when they saw my ankles all swollen. And then buy the right
things at the grocery store.
Counseling Strategies 285
The physician could continue by exploring what it will take for Linda to follow through on her
decision to tell her husband and to actually make the right purchases at the grocery store, and so on.
However, Lindas physician is determined that she had come a long way during this visit. He did not
want to frustrate her and also wanted to support her sense of autonomy and choice in deciding how
she would put these possibilities into action.
On a scale from 1 to 10, with 1 being the least ready you have been and 10 being the most ready you can
imagine being, how ready would you say you are today to try this eating plan?
For gauging the patients willingness to explore change (i.e., gauging the level of interest), the
word ready would be replaced by willing, and the question would be modified as follows:
... How willing would you say you are today to think about the information I am giving you?
This can also be done for the patients confidence that he or she can follow through on a plan:
... How confident are you today that you will be able to stick to your plan?
For happiness, satisfaction, motivation, health, support from family, and so on:
... Where would you say your level of happiness (satisfaction, motivation, health, support from family)
is today?
Okay, so where does that put you on the scale right now? ... What number would you give that?
The next step is critical to helping the patient identify a concrete goal and think about possible
behavioral solutions toward that goal. Let us assume that a patient is asked how hopeful he is about
his situation and that he has responded that he is at 6. Then the clinician asks:
What would be different about you or your life that would move you to 6 ?
286 Nutrition Therapy for Chronic Kidney Disease
This is also an opportunity to use the one thing intervention to increase specificity and focus:
What is one thing that could change or improve about you or your situation that would push you to
a6?
The emphasis here is on asking the patient to consider a hypothetical question: what would have
to happen to move his or her rating to the positive side of the scale. Framing the question in this
way and stressing just a half-point movement decreases the pressure many patients feel to change
everything all at once because it essentially gives them permission to consider small, reasonable
goals and manageable steps toward achieving those goals in the form of hypothetical possibilities.
Clinician: What would be different about you or your life that would move you to 4 ?
Charles: If I could control my sugar and blood pressure without giving things up.
Clinician: What might be one thing that could change or improve about you or your situation
that would push you up just that half a point?
Charles: A 4 eh? I guess if it didnt cost so much to eat healthy! Thats a big deal when you
live on a fixed income!
There are two essential points in this exchange that exemplify the nature of a solution-focused
approach. First, it would not be surprising if some clinicians decided to point out to Charles the dis-
crepancy between his refusal to quit smoking or change his diet and his 4 confidence rating that he
can become healthier without doing so. This may be useful in increasing his motivation to change.
However, such discrepancies are often obvious to patients, and pointing them out may only increase
the pressure they feel. Typically, the issue is that they do not know how to resolve the discrepancies
and feel stuck rather than being unaware of them. Second, Charles final response demonstrates
the importance of continuing to peel the layers of the onion. Given his previous response, some
clinicians may simply assume that Charles will say that not having to give anything up would make
things better; however, clinicians often find that asking that next question, along the same line, often
yields tangible results. While the clinician and patient still have work to do to move toward solu-
tions, the door to solution room has been opened because his response indicates he might prefer to
discuss dietary changes than his smoking and, most importantly, that he has at least explored the
possibility of making changes to his diet in the past.
Clinician: Sometimes when folks are dealing with so much the littlest of changes dont seem
to count for much, but they really do make a difference in the long run. I wonder what
could be the smallest change you could make and still be on a fixed income even if it didnt
seem like it would make a difference.
Charles: Small change ... . Hmmm ... well, my wife has been on me about my potato chips.
I suppose I could cut back on those. (Chuckling) I dont know if that would make much of
a difference!
Charles has just asserted that change, no matter how small, is still a possibility, and that he is
capable of making it when he is ready. Restraining the size of the proposed change reduces the
Counseling Strategies 287
pressure of the change process from being like a tidal wave over which the patient feels no control
to a cup of water over which the patient has control and can sip from when he chooses. Since this
is a statement rather than a question, it does not require a definitive response about his plan or pur-
chasing food; instead, it promotes imagination and hypothetical solutions regarding existing food
choices and options.
Clinician: Wow! Potato chips huh? So using that same scale of 110, how likely are you to cut
back on your chips for just two days this next week if you pick the days?
Charles: Scale of 110. ... (Laughing) Probably a 2 on that! ... Nah, Im probably at a 6, espe-
cially if I can pick the days. Itll have to be the weekdays because I like to have chips while
Im watching football and basketball on TV.
Clinician: Okay, Im impressed. What would it take to push you to a 6.5 for those two days?
Charles: I usually take the whole bag of chips and just keep eating them. I guess I could just
put some in a bowl and just eat those.
Clinician: Great idea! I wonder if there is something else that you could have on hand for
when you get to the bottom of the bowl in case you still have a hankering for the chips.
Charles: To be honest, yeah, well theyre still like chips, but my wife got some unsalted pret-
zels and I ate those a couple of times. She really wanted me to eat celery sticks like it said
in that pamphlet. I guess I could do that once or twice too.
Clinician: It sounds like you may have some options. Now what else can we bug you about,
or is that enough for today?
This dialogue illustrates how the conversation cycles back to a scaling question to concret-
ize small, manageable goals and hypothetical possibilities. The clinician does not impose a set
requirement or recommendations on the patient; instead, he or she poses his suggestions as I
wonder what would happen if questions that the patient can do with what he chooses. Fortunately
for the change process, framing issues in this hypothetical way reduces the pressure on the patient
and opens up a discussion of possibilities. Here, Charles comes up with several possibilities on
his own, and the clinician does not try to dictate how or when Charles should implement them.
The visit finishes with an affirmation that Charles has options, which he himself generated. The
clinician pairs this with a playful question intended to bring the visit to a close, but that, most
importantly, acknowledges both the challenges of trying to change and how much work the patient
did during that visit.
20.5 REFRAMING
A reframe redefines the problem as something inherently more positive. Because reframing makes
the problem seem more amenable to change, it can be a useful and empowering technique when the
patient seems to resist making changes. It is usually the case that the more complex is the problem,
the harder it is to change, and the more resistant the patient seems. So methods that diminish the
perceived potency of problems typically allow the patient to feel more hopeful and optimistic about
change.
For example, it is common for patients being counseled about smoking cessation to counter the
clinicians comments with an emphatic Im-not-interested-in-changing-anything type of response,
such as the following:
My father smoked all of his life, and he lived to be ... 85 years old.
This closes the door on productive health behavior counseling for clinicians who tend to get
revved up at this type of response and who want to probe for evidence that the father actually
experienced low quality of life and that smoking ultimately led to his death. This is often a fruitless
288 Nutrition Therapy for Chronic Kidney Disease
approach because there is no guarantee that the fathers perceived quality of life suffered and, more
importantly, it turns the conversation into a power struggle. It can be much more fruitful to respond
to the patient by saying:
So, smoking was a part of your fathers health care plan; what other things did your father do to live to
be 85 years old?
This statement and the question together reframe the fathers behavior (smoking) as normal for
him and turn the focus to other, less emotionally laden discussions of health behaviors, which the
clinician and patient can explore together. Many patients will respond as this patient did, by saying:
Thats a good question. Well, actually he did quit smokingwhen he was 75and walked two miles
almost every day at the mall with a friend of his.
Discussing a patients father rather than the patient himself can help loosen his defensiveness
about his own decisions and behavior enough to consider alternative points of view. Even if the
patient does not acknowledge the smoking, discussing other behaviors, such as physical activity
and eating, can suggest the possibility of making smaller changes that from the patients per-
spective seem more manageable. For example, about the other things his father did the patient
responds:
Oh, well he always said putting extra salt on your food was bad for you. And he worked every day on his
farm until he was 70 and then worked a large garden when the farm work was too much.
This response opens the doors for the clinician to explore what the patient feels were the motiva-
tion behind these behaviors; highlight them as health behaviors (i.e., diet and physical activity) and
then amplify them toward the patient by asking as follows:
What are your healthy habits when it comes to eating? What serves as your farm for physical activity
like your father had?
Many patients will respond, Hmmm ... I hadnt really thought about it like that before. The
potency of reframing questions is that they emphasize relationships with loved ones, especially
children, and this tends to increase patients self-awareness about the stakes of their behavior and
makes the discussion of that behavior, as well as the potential behavior change, more meaningful.
In essence, reframing the behavior as a life lesson takes the covert, private worry people may have
about the impact of their behavior on their loved ones and makes it an overt, public reality that can-
not be as easily suppressed.
For those patients without children or dependents, an alternative reframing question can be asked
that creates the same frame of thought:
When you get to that point in your life when you are looking back on what you have accomplished and
what your legacy has been, what do you want people to be able to say about you?
Counseling Strategies 289
Where would you like to be in six months? A year? ... Five years?
What will you be doing?
Who will be there?
What things that you are doing now put you closer to that vision?
Lets pretend that/when you wake up one day and your symptoms are controlled, people are off
your back, youve only gone to your doctor for regular visits, etc. What would you guess would
be one thing that you would look back and say you did to make that more likely to happen?
Six months (or one year) from now what do you want to be able to look back and say you
accomplished between now and then?
What will you notice is different about yourself at the time you are ready to make a change?
What will be a sign that something different needs to happen or that you need to make a
change?
20.7 CONCLUSION
This chapter has elucidated a framework of solution-focused counseling strategies for health behav-
ior change, in general, and for diet counseling, in particular. These techniques are versatile and
can be adapted to a variety of behavior change issues, as well as to various interpersonal styles. It
is certainly not a comprehensive review of SFT or of the circular questioning interviewing style.
It provides a practical explanation of several valuable techniques for initiating and supporting the
behavior change process. The intention is to introduce readers to the potential clinical utility of a
solution-focused approach as an alternative to or in addition to other established and promising
models of dietary health behavior counseling (Spahn et al., 2010).
REFERENCES
Berg, I. 1994. Family Based Services: A Solution Focused Approach. New York: WW Norton.
Cheng, M. 2007. New approaches for creating the therapeutic alliance: Solution-focused interviewing, motiva-
tional interviewing, and the medication interest model. Psychiatr Clin North Am. 30:157166.
deShazer, S. 1988. Investigating Solutions in Brief Therapy. New York: WW Norton
Fleuridas, C., Nelson, T., and Rosenthal, D. 1986. The evolution of circular questions: Training family thera-
pists. J Marital Fam Ther. 12:113127.
Giorlando, M. and Rae, J. 1997. On becoming a solution-focused physician: The MED-STAT acronym. Fam
Syst Health. 15:361373.
Greenberg, G., Ganshorn, K., and Danilkewich, A. 2001. Solution-focused therapy. Counseling model for busy
family physicians. Can Fam Phys. 47:22892295.
McGee, D., Del Vento, A., and Beavin Bavelas, J. (2005). An interactional model of questions as therapeutic
interventions. J Marital Fam Ther. 31:371384.
Mitchell, C. 2005. Effective Techniques for Dealing with Highly Resistant Clients. Johnson City, TN: Clifton
W. Mitchell Publishing.
Poon, V. 1997. Short counseling techniques for busy family doctors. Can Fam Phys. 43:705713.
Spahn, J., Reeves, R., Keim, K., et al. 2010. State of the evidence regarding behavior change theories and strate-
gies in nutrition counseling to facilitate health and food behavior change. J Am Diet Assoc. 110:879891.
Walter, J. and Peller, J. 1992. Becoming Solution-Focused in Brief Therapy. New York: Brunner/Mazel.