ccpc15 Principles Renal Clearance Acute Kidney Renal Replacement Workbook

Principles of Estimating Renal
Clearance, Acute Kidney Injury,

and Renal Replacement in the
Critically Ill Patient
Michael L. Bentley, Pharm.D., FCCP, FCCM, FNAP
Carilion Clinic
Roanoke, Virginia
Principles of Estimating Renal Clearance, Acute Kidney Injury, and Renal Replacement in the Critically Ill Patient
Principles of Estimating Renal

Clearance, Acute Kidney Injury,
and Renal Replacement in the
Critically Ill Patient
Michael L. Bentley, Pharm.D., FCCP, FCCM, FNAP
Carilion Clinic
Roanoke, Virginia
ACCP Updates in Therapeutics® 2015: Critical Care Pharmacy Preparatory Review Course
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Learning Objectives RRT Renal replacement therapy

RIFLE Risk, injury, failure, loss, end-stage renal
1. Discuss the limitations of using measured creatinine disease
to estimate creatinine clearance (CrCl). SLED Sustained low-efficiency dialysis
2. Understand how CrCl and glomerular filtration rate Vd Volume of distribution
differ.
3. List common equations used to estimate CrCl.
4. Define acute kidney injury (AKI). Self-Assessment Questions
5. List common categories and give examples of drug- Answers and explanations to these questions may be
induced AKI. found at the end of this chapter.
6. With respect to renal replacement therapy, define
diffusion and convection and describe their role in Questions 1–3 pertain to the following case.
blood purification. G.W. is a 42-year-old obese man (height 64 inches,
7. Discuss the role of dialysate and replacement fluids weight 112 kg) with stable chronic kidney disease
in continuous renal replacement therapy (CRRT). (CKD). His creatinine clearance (CrCl) is estimated
8. Describe drug-dosing concepts in CRRT and using the Cockcroft-Gault (CG) equation.
sustained low-efficiency dialysis/extended daily
dialysis. 1. Which is one of the most important considerations
when using this equation?
A. CG does not account for the sex of a patient.
Abbreviations in This Chapter B. Strongly consider using adjusted body weight
in the calculation because this patient is obese.
ACEI Angiotensin-converting enzyme inhibitor C. CG can be used only if IDMS (isotope dilution
ADQI Acute Dialysis Quality Initiative mass spectroscopy)-standardized creatinine
AIN Acute interstitial nephritis (Cr) is used.
AKI Acute kidney injury D. CG is only validated to estimate CrCl in
AKIN Acute Kidney Injury Network patients with acute kidney injury (AKI).
ARB Angiotensin receptor blocker
ARF Acute renal failure 2. G.W.’s CrCl is estimated using the Modification
ATN Acute tubular necrosis of Diet in Renal Disease (MDRD) study equation.
CG Cockcroft-Gault (equation) Which is one of the most important considerations
COX-2 Cyclooxygenase-2 when using this equation?
CKD Chronic kidney disease A. It has been studied and validated in patients
CKD-EPI Chronic Kidney Disease Epidemiology with stable CKD.
Collaboration B. It has been studied and validated in elderly
Cr Creatinine patients (those older than 70 years).
CRRT Continuous renal replacement therapy C. In patients with glomerular filtration rates
CVVH Continuous venovenous hemofiltration (GFRs) greater than 60 mL/minute per 1.73m2,
CVVHD Continuous venovenous hemodialysis it overestimates clearance.
CVVHDF Continuous venovenous hemodiafiltration D. Compared with CG and measured CrCl,
EDD Extended daily dialysis the MDRD study equation overestimates
GFR Glomerular filtration rate clearance.
ICU Intensive care unit
IHD Intermittent hemodialysis 3. G.W.’s CrCl is estimated using the Chronic Kidney
MDRD Modification of Diet in Renal Disease Disease Epidemiology Collaboration (CKD-EPI)
(study) equation. Which depicts one of the most important
MW Molecular weight considerations when using this equation?
NSAID Nonsteroidal anti-inflammatory disease
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A. It has been studied and validated in patients 7. E.R. continues to worsen. He is now febrile with
with AKI. an increasing white blood cell count (WBC). You
B. It has been studied and validated in patients are asked to dose cefepime while he is receiving
who are 12 years or older but younger than 70 CVVH. Which would be the best place to begin
years. looking for dosing recommendations?
C. It uses serum creatinine (SCr), age, and race, A. Intermittent hemodialysis (IHD) guidelines.
but not sex, in its calculation. B. Package insert.
D. Compared with MDRD, it is more accurate C. Primary literature/dosing summaries.
when the GFR is greater than 60 mL/minute D. Estimates using an estimated sieving
per 1.73m2. coefficient.
Questions 4–7 pertain to the following case. 8. Which drug property is most important to consider
E.R. is a 67-year-old man admitted to your intensive care when estimating whether a drug will be removed by
unit (ICU) several days ago with acute respiratory failure. continuous renal replacement therapy (CRRT)?
He required mechanical ventilation and was placed on
A. Protein binding.
empiric antibiotics to cover likely community-acquired
B. Molecular weight (MW).
pneumonia. During the past 5 days, his renal function
C. Volume of distribution (Vd).
has worsened (SCr on admission 0.6 mg/dL; today,
D. Drug charge.
2.4 mg/dL.). He now requires renal replacement with
continuous venovenous hemofiltration (CVVH). Current
medications include ceftriaxone, azithromycin x 2 doses
only, enoxaparin, and ranitidine. As a pharmacist, you
are asked to evaluate E.R. for a possible cause of drug-
induced AKI. You determine that the most likely drug is
ceftriaxone.
4. Through which mechanism is ceftriaxone most

likely to cause AKI?
A. Acute tubular necrosis (ATN).
B. Acute interstitial nephritis (AIN).
C. Glomerulonephritis.
D. Tubular precipitation.
5. Using the AKIN staging, which best describes the

stage of AKI that E.R. is in?
A. Stage 1.
B. Stage 2.
C. Stage 3.
D. Unable to determine because urine output is
not provided.
6. Which best describes the principle for clearance

used for solute removal during CVVH?
A. Convection.
B. Diffusion.
C. Both convection and diffusion.
D. Membrane binding.
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I. MEASUREMENT OF KIDNEY FUNCTION
A. Measuring GFR
1. Several exogenous compounds can be used to measure GFR, but they have limited clinical application,
given their technically difficult administration technique, limited availability, and cost.
2. Although they are a less accurate measure of GFR, endogenous substances (i.e., Cr) are used clinically.
3. Estimated GFR urinary clearance of Cr can be determined by collecting urine over a 24-hour or shorter
period. However, this, too, has limited utility, given the frequent collection errors and delay in results.
B. Limitations to Using SCr for Estimating GFR

1. Measured SCr is the product of what is produced and what is excreted. Cr is a byproduct of muscle
metabolism and is influenced by muscle mass and diet, which may vary between individuals and affect
estimated clearance.
2. Reaching a steady-state SCr concentration is often unpredictable in critically ill patients because the Cr
production rate, it’s Vd, and the elimination rate may vary, further complicating drug-dosing estimates
when SCr is used to estimate clearance.
C. Estimating CrCl (Table 1)

1. CG equation
a. Although several equations for estimating CrCl have been proposed, CG has historically been
used.
b. Using body weight would seem logical, given the relationship between muscle metabolism and
Cr production. However, for patients who are overweight, obese, or morbidly obese, using total
body weight will likely overestimate CrCl. Although a consensus has not been reached, using an
adjusted weight (with a factor of 0.4) provides a more accurate measurement, compared with Cr
collected over 24 hours, than actual or ideal body weight in this patient group.
2. The MDRD study equation (estimated glomerular filtration rate [eGFR])
a. This equation was developed from a sample of patients with CKD using the urinary clearance of
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I iothalamate.
b. It has been validated in a wide population, including whites and African Americans, between 18
and 70 years of age with reduced renal function (less than 60 mL/minute per 1.73m2). However,
these results should be interpreted with caution because most studies do not compare actual
clearance.
c. In individuals with GFRs greater than 60 mL/minute per 1.73m2, the MDRD equation
underestimates measured GFR.
d. MDRD should not be used when SCr is unstable (i.e., in hospitalized patients with rapidly
changing renal function or in those with AKI).
3. CKD-Epidemiology Collaboration (CKD-EPI) Equation
a. CKD-EPI uses the same four variables (SCr, age , sex, and race) as the MDRD Study equation for
predicting GFR in adults ≥ 18 years of age and has been shown to be more accurate when GFR is
> 60 ml/min per 1.73 m2 than MDRD.
b. Similar to the MDRD Study equation, and other equations used to estimate GFR from SCr,
CKD-EPI should be used with caution in patients with non-steady-state creatinine production and
elimination and in those with altered production of creatinine (ex., altered diets or muscle mass).
c. It has not been adequately validated in the elderly or in African Americans with higher GFR’s.
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Table 1. Common Equations for Estimating GFR

CockcroftGault
CrCl (mL/min) = (140 − age (years) x weight (kg) x 0.85 [female])/(SCr (mg/dL) x 72)
MDRD (four-variable) study equation

GFR (mL/min per 1.73m2) = 186.3 x SCr-1.154 x age-0.203 x 1.212 [African American] x 0.742 [female]
MDRD (four-variable) study equation using IDMS SCr

GFR (mL/min per 1.73m2) = 175.6 x SCr-1.154 x age-0.203 x 1.212 [African American] x 0.742 [female]
CKD-EPIa
GFRα (ml/min per 1.73m2) = 141 x min (SCr/k,1)α x max (SCr/k,1)-1.209 x 0.993Age x 1.159 [black] x 1.018 [female]
Abbreviations: CKD-EPI, Chronic Kidney Disease-Epidemiology Collaboration; CrCl, creatinine clearance; GFR, glomerular filtration rate;
IDMS, isotope dilution mass spectroscopy; MDRD, Modification of Diet in Renal Disease
a
For CKD-EPI, k is 0.7 for females and 0.9 for males, α is -0.329 for females and -0.411 for males, min is the minimum of SCr/k or 1, and max
is the maximum of SCr/k or 1 and age is years.
D. Considerations for Drug Dosing

1. CKD: In patients with reduced kidney function, a dose adjustment in renally eliminated medications
may be necessary. Information is often conflicting between what is recommended by the manufacturer
and what is found in the postmarketing studies.
a. Drug-dosing recommendations: In 2010, the National Kidney Disease Education Program
recommended that for adults, drug dosing be based on either the MDRD study equation (eGFR) or
CrCl using the CG equation.
b. For very large or small patients, the eGFR should be multiplied by the estimated body surface area
to give the eGFR in milliliters per minute.
2. AKI
a. Drug dosing in critically ill patients with AKI has been problematic. Several issues are unique to
this population, including (1) rapid changes in SCr and the time needed to reach a new steady-state
concentration; (2) influence of aggressive volume resuscitation – increased Vd; (3) increase in Cr
secretion in early AKI; (4) increased non-renal clearance; (4) lack of evidence-based dosing; and
(5) influence of renal replacement therapies (RRTs).
b. There is growing evidence that AKI alters the non-renal clearance of several medications. It is
likely that the cytochrome P450 (CYP) enzymatic pathways of several organs are involved, as
are uptake and efflux transporters. The impact of altered pathways on drug dosing is in its early
stages of development. Currently, there are no global adjustment recommendations; however, the
pharmacist should be aware that drug-specific data might be limited.
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Patient Cases
1. R.J. is a 42-year-old man admitted to your ICU with septic shock. Before this admission, he had been healthy,
taking no chronic medications. An initial basic metabolic panel showed an SCr of 2.2 mg/dL and a blood urea
nitrogen (BUN) of 20 mg/dL. You wish to estimate his CrCl. Which best describes some of the limitations
to using R.J.’s current SCr?
A. There are no limitations.
B. Drug-dosing recommendations consider acute changes in renal function.
C. R.J.’s SCr is likely not at steady state.
D. The laboratory will likely be unable to report a value, given R.J.’s acute change.
2. S.B. is a 69-year-old African American woman with a history of diabetes, hypertension, and stable CKD. You
wish to estimate her CrCl for drug dosing. Which equation is most appropriate?
A. CG.
B. MDRD.
C. Either CG or MDRD.
D. CKD-EPI.
II. ACUTE KIDNEY INJURY
A. Epidemiology
1. Defining the incidence of AKI has been a limiting factor in moving patient care and research forward.
Reasons why this has been problematic include varying causes of and dissimilarities among those
developing acute renal failure (ARF) and timing of onset.
2. Patients presenting with ARF at the time of hospital admission is uncommon, accounting for about 1%
of hospital admissions; however, community-acquired ARF has been poorly studied.
3. Hospital-acquired AKI, although more common than community-acquired AKI, occurs infrequently
(i.e., in 1.9%–7% of patients admitted to a medical center, except in elderly patients, for whom AKI
has been reported to be as high as 60%).
4. Critically ill patients are at greatest risk of AKI.
a. ARF has been estimated to occur in 20%–30% of all patients admitted to an ICU.
b. Severe sepsis and septic shock are common causes of ATN, which is a leading cause of AKI in
critical illness.
c. Other common risk factors include use of intravenous radiocontrast agents, major surgery
(especially cardiothoracic), nephrotoxic medications, and chronic medical conditions (e.g., history
of CKD, congestive heart failure, and diabetes mellitus). Most patients have more than one risk
factor.
B. Definitions (Table 2a and 2b)

1. During the past several decades, many definitions have been used to define ARF, making it difficult
to compare patient populations across studies. In 2002, the Acute Dialysis Quality Initiative (ADQI)
workgroup developed the RIFLE (risk, injury, failure, loss, end-stage renal disease) definition and
staging system.
a. RIFLE categorizes ARF into three grades of increasing severity and two clinical outcomes.
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b. For the acronym RIFLE, “risk” is defined as oliguria for more than 6 hours or an increase in SCr
to 1.5 times baseline or greater. As renal function continues to worsen, the criteria for “injury” and
“failure” are met. Clinical outcomes (“loss” and “end-stage renal disease”) are defined by the need
for RRT for more than 4 weeks and more than 3 months.
2. According to emerging data suggesting that small changes in renal function (SCr of 0.3 mg/dL or
greater) lead to worse outcomes, the ADQI workgroup formed the Acute Kidney Injury Network
(AKIN).
a. This group defined AKI, using a staging system of 1–3, as a reduction in kidney function that
occurs over no more than 48 hours using measures of SCr and urine output.
b. Stage 1 is an absolute increase in the SCr level of 0.3 mg/dL or greater or a relative increase to
1.5- to 2-fold above baseline or documented oliguria less than 0.5 mL/kg/hour for more than 6
hours, despite adequate fluid resuscitation.
c. Similar to RIFLE, stages 2 and 3 are met with worsening SCr and urine output.
d. The main difference between the two staging systems is that the AKIN definition initially includes
a lesser degree of SCr elevation to diagnose AKI.
e. In patients requiring RRT, AKIN stage 3 is met regardless of the stage they are in at the time of
RRT initiation.
f. Several studies have validated these criteria and show that the more severe the RIFLE class or
AKIN stage, the worse the clinical outcome.
Table 2a. Criteria for AKI

RIFLE Class SCr Criteria/GFR UOP Criteria
R Increase to 1.5-fold or GFR decrease > 25% from < 0.5 mL/kg/hour for 6 hours
baseline
I Increase to 2-fold or GFR decrease > 50% from baseline < 0.5 mL/kg/hour for 12 hours
F Increase to 3-fold, GFR decrease > 75% from baseline or < 0.3 mL/kg/hour for 24 hours or
SCr ≥ 4 mg/dL (acute increase of at least 0.5 mg/dL) anuria for 12 hours
L Complete loss of function for > 4 weeks
E Complete loss of function for > 3 months
Table 2b. Criteria for AKI

AKIN Stage SCr Criteria UOP Criteria
1 Increase to 1.5- to 2-fold above baseline or by 0.3 mg/dL < 0.5 mL/kg/hour for 6 hours
2 Increase to 2- to 3-fold above baseline < 0.5 mL/kg/hour for 12 hours
Increase > 3-fold above baseline or ≥ 4 mg/dL with an < 0.3 mL/kg/hour for 24 hours or
3a
acute rise of ≥ 0.5 mg/dL anuria for 12 hours
a
Individuals who receive renal replacement therapy (RRT) are considered to have met the criteria for stage 3, irrespective of the stage they are in
at the time of RRT.
AKI = acute kidney injury; AKIN = Acute Kidney Injury Network; RIFLE = risk (R), injury (I), failure (F); loss (L); end-stage kidney disease (E);
UOP = urine output.
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3. In AKI and CKD, there are many reasons that changes may occur in the function and structure of the
kidney. Moreover, even though changes may occur, it is possible that neither the AKI definition nor the
CKD definition is met.
a. In its 2012 clinical practice guideline, KDIGO (Kidney Disease: Improving Global Outcomes)
proposed an operational definition for acute kidney disease (AKD). The purpose was to identify
patients with AKD in an attempt to offer therapies to restore kidney function and reverse kidney
damage.
b. An operational definition of “no known kidney disease” (NKD) was also included for those not
meeting other criteria.
c. Table 3 provides definitions of AKI, CKD, AKD, and NKD.
Table 3. Definition of AKI, CKD, AKD, and NKD According to Function and Structure
Functional Criteria Structural Criteria
(change in SCr, GFR,a or UOP) (damageb or no damage and duration)
↑ in SCr by 50% within 7 days
Or
AKI ↑ in SCr by 0.3 mg/dL within 2 days No criteria
Or
Oliguria
GFR < 60 mL/min per 1.73m2 Kidney damage for > 3 months
CKD
for > 3 months
AKI
Or
GFR < 60 mL/min per 1.73m2 for
AKD
< 3 months Kidney damage for < 3 months
Or
↓ in GFR by ≥ 35% or ↑ in SCr by > 50% for < 3 months
NKD GFR ≥ 60 mL/min per 1.73m2, stable SCr No damage
a
Assessed from measured or estimated GFR.
b
Kidney damage is assessed by pathology, biomarkers (urine or blood), imaging, and kidney transplantation (for CKD).
AKD = acute kidney disease and disorders; AKI = acute kidney injury; CKD = chronic kidney disease; NKD = no known kidney disease.
C. Differential Diagnosis
1. AKI cannot be diagnosed with a single specific test.
2. A thorough history and complete examination should be complete, including:
a. Rate of loss, symptoms, and coexisting diseases
b. A comprehensive review of current and recent medications should be completed. Drug-related
injury is a leading cause of AKI.
3. Chemistries (BUN, Cr, serum electrolytes, albumin, and a complete blood cell count) and a urinalysis
(microscopy, sodium, Cr, and osmolality) may assist in determining the type of failure (e.g., prerenal,
intrinsic, postrenal).
4. If not present, a bladder catheter should be inserted. If present, it should be evaluated for obstruction.
5. Abdominal compartment syndrome should be ruled out if clinically suspected. Acute oliguria and AKI
are the result of increasing renal outflow pressure and reduced renal perfusion.
6. Routine use of renal ultrasonography is limited because most ICU-related AKI is associated
with prerenal azotemia and ATN. However, it may be useful in high-risk patients, those from the
community, or after an initial evaluation fails to reveal the cause of AKI.
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7. Renal biopsies have limited usefulness but may be necessary. They are most useful in intrinsic renal
failure not associated with ATN.
D. Causes of Drug-Induced AKI (Table 4) – Drug-induced AKI can result when medications are given to an
otherwise normal, healthy patient, but injury is more common in the setting of several insults (i.e., disease
plus drug) to the kidney.
1. Prerenal
a. Decreased blood flow to the kidney, which can result in injury, may be caused by several
mechanisms. A reduction in intravascular volume from shock, resulting in decreased perfusion
pressure, is most common.
b. Drugs typically cause prerenal AKI by one of two mechanisms: they either decrease blood flow
to the kidney or influence intraglomerular hemodynamics. Included among drugs affecting blood
flow is the excessive use of loop diuretics and several cardiovascular medications.
i. Loop diuretics can alter extracellular volume by causing excess volume depletion or reduced
effective circulation.
ii. Cardiac medications can decrease cardiac output (e.g., those having a negative inotropic
effect, especially in the setting of severe or decompensated heart failure) or alter systemic
vascular resistance (e.g., antihypertensive medications that reduce systemic vascular
resistance by causing vasodilatation).
iii. Normal hemodynamics of the kidney is maintained, in part, by vasodilatation of the afferent
or vasoconstriction of the efferent arterioles. Increased renal vascular resistance or decreased
transcapillary pressure can occur after medications that affect these vessels are administered.
iv. Vasodilatation of the afferent arteriole is partly caused by the effects of prostaglandins.
Medications that decrease prostaglandin synthesis decrease the ability of the afferent arterioles
to vasodilate. Common medications known to inhibit this synthesis are the nonsteroidal anti-
inflammatory drugs (NSAIDs) and cyclooxygenase-2 (COX-2) inhibitors.
v. Vasoconstriction of the efferent arteriole is mediated through angiotensin II. Drugs that block
angiotensin II (e.g., angiotensin-converting enzyme inhibitors [ACEIs] and angiotensin
receptor blockers [ARBs]) prevent effective efferent vasoconstriction, leading to decreased
transcapillary pressure. As a result, the kidney loses its ability to maintain adequate perfusion
pressure.
vi. Calcineurin inhibitors (e.g., cyclosporine and tacrolimus) have been associated with prerenal
AKI, although the exact mechanism has not been well established. Both afferent and efferent
vasoconstriction may be involved. These drugs have also been associated with AIN.
2. Renal (Intrinsic) – Drug-induced intrinsic AKI can be caused by several mechanisms and is the result
of injury to the renal tubules, glomerulus, vascular structures, interstitium, or obstruction of the renal
tubules.
a. Tubular injury
i. ATN is common in critical illness.
ii. Tubular injury results most often from prerenal insults (e.g., prolonged hypotension) or from
nephrotoxic agents.
iii. Intravenous contrast agents, aminoglycosides, amphotericin B, and the antiretroviral agents
are most commonly associated with ATN.
b. Interstitial injury
i. In the absence of AKI, AIN is uncommon. It occurs in only 1%–3% of all renal biopsy-proven
cases. In the presence of AKI, the incidence is higher and accounts for 15%–27% of cases.
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ii. Interstitial injury is characterized by inflammatory infiltrates and edema within the
interstitium. The clinical presentation is nonspecific and may include fever and rash with
laboratory evidence of eosinophilia; however, this “classic triad” occurs in only 10%–30% of
patients.
iii. Drug-induced AIN represents more than 75% of cases. Other causes include infections
(5%–10%), idiopathic (5%–10%) or associated with systemic diseases (10%–15%).
iv. Several medications have been associated with AIN, including antimicrobials (e.g.,
penicillins, cephalosporins, sulfonamides, ciprofloxacin, vancomycin), NSAIDs and COX-
2 inhibitors, omeprazole, lansoprazole, phenytoin, valproic acid, cimetidine, ranitidine,
diuretics, and cocaine.
v. Renal recovery is usually complete once the offending agent has been removed; however,
it may take weeks to several months. AIN associated with the chronic use of calcineurin
inhibitors is often irreversible. In addition to removing the offending agent, steroids may be
useful in limiting damage. However, steroid use remains controversial.
c. Glomerular injury
i. Acute glomerulonephritis (GN) is associated with inflammation and proliferation of
glomerular tissue that results in damage to the basement membrane, mesangium, or capillary
endothelium.
ii. Non-drug causes of GN include systemic disorders such as lupus, hepatitis, and vasculitis
iii. Drug-associated GN may include NSAIDs, ampicillin, rifampin, lithium, penicillamine,
hydralazine, gold, mercury, and heroin.
iv. Fever, malaise, and/or arthralgia may occur.
v. Renal indices are non-specific and may mirror prerenal disease.
vi. It can be fatal and result in irreversible kidney damage.
vii. Treatment includes removal of the likely agent and may include the use of
immunosuppressant’s, which may limit disease.
d. Vascular injury
i. Injury to the renal vascular system is more likely to be caused by either microvascular or
macrovascular disease than induced by drugs.
(a) AKI associated with microvascular disease is usually associated with thrombotic
thrombocytopenic purpura, hemolytic uremic syndrome, and HELLP syndrome
(hemolysis, elevated liver enzymes, and low platelets). It is often the result of glomerular
capillary thrombosis.
(b) AKI associated with macrovascular disease is usually associated with renal artery
occlusion or major abdominal aortic disease.
ii. Injury is often irreversible; it should be considered in patients with recent vascular procedures.
e. Intratubular obstruction
i. Intratubular obstruction is uncommon and can be associated with non-drug or drug causes.
ii. Non-drug causes include multiple myeloma and tumor lysis syndrome. Injury results from
monoclonal light chains and uric acid that obstructs the tubule.
iii. Drug-associated intratubular obstruction can result from the calcium oxalate crystals
associated with ethylene glycol ingestion.
3. Postrenal
a. AKI associated with postrenal causes is uncommon in critically ill patients because a bladder
catheter is usually in place. If an obstruction is suspected, it should be ruled out by evaluating the
catheter, or by placing one if absent.
b. The obstruction may be in the luminal wall or extrinsic to the urinary tract. To cause AKI from
upper tract obstruction, the blockage must be bilateral or affect a single functioning kidney.
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c. Medications known to cause tubular obstruction include acyclovir, methotrexate, sulfadiazine,

foscarnet, indinavir, tenofovir, and triamterene.
d. Risk factors include preexisting renal dysfunction and poor hydration.
e. Ultrasonography is the gold standard test for diagnosis.
Table 4. Location, Mechanism of Injury, and Potential Causes of Drug-Induced Acute Kidney Injury
Prerenal
Hemodynamic alterations
• ↓ Cardiac output (e.g., negative inotropic drugs)
• ↓ Systemic vascular resistance (e.g., vasodilators)
• ↑ Renal vascular resistance – ex. NSAIDS, COX-2 inhibitors, cyclosporine, tacrolimus)
• ↓ Transcapillary pressure – ex. ACEIs; ARBs
Extracellular volume depletion – ex. excessive diuretic use
Renal (Intrinsic)
• Acute tubular necrosis – ex. AG, amphotericin B, contrast agents, cocaine, antiretrovirals (adefovir,
cidofovir, foscarnet, and tenofovir)
• Acute interstitial nephritis – ex. antimicrobials (penicillins, cephalosporins, sulfonamides, ciprofloxacin,
vancomycin, macrolides, tetracyclines, and rifampin), COX-2 inhibitors, NSAIDs, PPIs (omeprazole,
lansoprazole, phenytoin, valproic acid, diuretics, cocaine, H2RA (cimetidine, ranitidine)
• Glomerulonephritis – ex. NSAIDs, antimicrobials (ampicillin, penicillamine, rifampin), lithium,
hydralazine, gold, mercury, heroin
Postrenal
Precipitation of drug in renal tubules – ex. sulfonamides, antiretrovirals (acyclovir, foscarnet, indinavir,
tenofovir), methotrexate, sulfadiazine, triamterene, vitamin C at large doses
Bladder Obstruction
Ex. anticholinergics
ACEI = angiotensin-converting enzyme inhibitor; AG = aminoglycoside; ARB = angiotensin receptor blocker; COX-2 = cyclooxygenase-2; GN =
glomerulonephritis; H2RA = histamine-2 receptor antagonist; NSAIDs = nonsteroidal anti-inflammatory drug; PPI = proton pump inhibitor.
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Patient Case
Questions 3–5 pertain to the following case.

F.B. is a 68-year-old, 70 kg, man admitted to your ICU with fever, elevated WBC, respiratory failure requiring
mechanical ventilation, and norepinephrine to support his blood pressure. His medical history is significant for
chronic back pain, for which he takes acetaminophen as needed; diabetes, for which he takes glipizide; and
enalapril for hypertension. Before this admission, he had been otherwise healthy, seeing his primary care provider
about 1 week ago. At that time, his blood pressure was 140/80 mm Hg, and his A1C was 5.2. This laboratory
workup was also unremarkable: WBC 5.0 x 103 cells/mm3, BUN 7 mg/dL, and SCr 0.9 mg/dL. Today, his WBC
is 24 x 103 cells/mm3, BUN 38 mg/dL, and SCr 3.2 mg/dL, with about 325 mL of urine output since his admission
24 hours ago.
3. Which best describes F.B.’s AKI?

A. RIFLE class R.
B. AKIN stage 1.
C. RIFLE class F or AKIN stage 3.
D. RIFLE class E or AKIN stage 3.
4. Which medication is most likely contributing to his AKI?

A. Enalapril.
B. Glipizide.
C. Acetaminophen.
D. Enalapril and glipizide equally.
5. When evaluating F.B.’s potential causes of AKI, which additional information or test would be most important
to consider or obtain?
A. Rate of loss, symptoms, and coexisting diseases and medications.
B. Renal evaluation using ultrasonography because this can determine the cause of AKI in most patients.
C. Review of blood chemistries because this will likely determine the cause of injury.
D. Renal evaluation using biopsy.
III. RENAL REPLACEMENT THERAPIES
A. General Approaches to Managing AKI

1. Once injury has occurred, therapy consists of supportive care and limiting additional insults, including
nephrotoxins.
2. In patients with shock, adequate fluid resuscitation should be initiated to restore effective circulation
without producing volume overload.
3. No specific pharmacologic therapy is effective in treating or reversing AKI.
4. Metabolic control and patient volume should be followed closely, and RRT is initiated when other
approaches have failed.
5. Few data exist to suggest the timing or modality of therapy. Historically, RRT has been offered when
severe acidosis (A) or electrolyte abnormalities – hyperkalemia (E) are present, in the setting of certain
intoxicates (I), refractory volume overload (O), or symptomatic uremia (U). The AEIOUs of initiating
RRT. Whether RRT is initiated largely depends on the treating physician, but recent evidence suggests
that early initiation is associated with decreased mortality.
2-324
B. Mode of Renal Replacement for AKI

1. Differing modes of RRT include IHD, peritoneal dialysis (PD), CRRTs, and extended daily dialysis
(EDD) or sustained low-efficiency dialysis (SLED).
2. Solute and water transport through a semipermeable membrane assists in defining the mode of RRT.
3. Solute removal requires diffusion, convection, or its combination.
C. Intermittent Hemodialysis
1. IHD has historically been used to manage critically ill patients with AKI.
2. However, hypotension can occur in about 20%–30% of patients treated with IHD.
3. IHD may also be problematic in patients with head trauma or hepatic encephalopathy because of rapid
solute removal from the intravascular space, causing cerebral edema and increased intracranial pressure.
D. Continuous Renal Replacement Therapies

1. CRRT is the most commonly used modality of RRT in hemodynamically unstable ICU patients.
2. CRRT modalities include CVVH, continuous venovenous hemodialysis (CVVHD), or continuous
venovenous hemodiafiltration (CVVHDF).
3. SCUF, or slow continuous ultrafiltration, is another type of CRRT that removes fluid without the
need for replacement solutions. It has no impact on the removal of waste products (e.g., BUN) or
electrolytes and cannot correct acid-base abnormalities.
4. Solute clearance during CVVHD occurs by diffusion. Diffusion is the movement of solutes from
an area of higher solute concentration to an area of lower concentration. A concentration gradient is
produced by running an electrolyte solution (i.e., dialysis fluid with a flow rate of 17–40 mL/minute)
countercurrent to the flow of blood. Small-molecular-weight solutes are cleared efficiently.
5. Solute clearance during CVVH occurs by convection, and the ultrafiltration rate determines the
clearance rate for most solutes. Convection uses the concept of “solute drag” and is capable
of removing both small- and large-molecular-weight solutes. Solute removal occurs when the
transmembrane pressure drives water and solute across a semipermeable membrane. This process
involves the addition of replacement fluid to replace the excess volume that is being removed and
replenish the desired electrolytes.
6. For CVVHDF, solute removal is by convection (i.e., CVVH) and diffusion (i.e., CVVHD).
E. SLED or EDD
1. These therapies are provided using conventional hemodialysis machines with low blood-pump speeds
(around 200 mL/minute) and low dialysate flow rates (around 300 mL/minute) for extended periods:
6–12 hours a day versus 3–4 hours for IHD or 24 hours for CRRT.
2. Similar to CRRT, they allow for improved hemodynamic stability by producing gradual solute and
volume removal compared with IHD.
3. These therapies have certain advantages over CRRT. They produce high solute clearances using
existing IHD machines eliminating the need for external solutions and allow “time away” when
various diagnostic and therapeutic procedures are needed. Disadvantages include limited data on drug
clearance.
F. Choosing a Mode
1. Data are conflicting regarding the renal replacement mode of choice for critically ill patients.
2. Outcomes such as mortality and renal recovery appear to be no different between IHD and CRRT;
however, most studies are limited by design, patient characteristics, and crossover between different
modalities.
2-325
G. CRRT and Drug-Dosing Concepts

1. Drug proprieties that influence removal during CRRT include protein binding, MW, and Vd. Drug
charge is less important.
a. The ability of a drug to bind to plasma protein (i.e., albumin) greatly influences how it is removed
by CRRT. Removal is inversely proportional to the percent bound (i.e., the higher the percent
bound, the less removed). Protein binding affects removal for both convection and diffusion.
b. In the absence of significant protein binding, the MW of most drugs has little impact on its overall
clearance. Removal can be significant during CVVH because this therapy effectively removes
drugs with an MW less than 15,000 kDa, and the pore sizes of most membranes are between
20,000 and 30,000 kDa, allowing drugs to pass freely. During CVVHD, the greatest impact on
drug clearance occurs with drugs having an MW less than 500 kDa. As MW increases, clearance
is reduced. Given that most drugs have an MW of less than 500 kDa, CVVH, CVVHD, and
CVVHDF result in significant drug removal if protein binding is low.
c. Vd is less of an issue with CRRT compared with other RRTs. Because CRRT uses slower flow
rates, time is allowed for drugs to equilibrate between body compartments. Drugs with a Vd less
than 0.6 L/kg have a greater potential for removal.
2. CRRT modalities and their influence during therapy
a. CVVH
i. Solute removal during CVVH is by convection. Convection is influenced by the membrane
pore size; the free fraction of drug, as discussed earlier; and the ultrafiltration rate.
ii. The ability of a substance to pass through a membrane by convection is termed sieving
coefficient (SC). The SC ranges from 0 to 1. An SC of 1 represents free movement, whereas
an SC of 0 represents no movement across a filter.
iii. SC can be calculated using a ratio of measured drug or other solute in the ultrafiltrate to its
concentration in the plasma, SC = CUF/Cp, where CUF is concentration in the ultrafiltrate and Cp
is concentration in the plasma.
iv. If a measured SC is not available, it can be estimated using the percent unbound to albumin,
SC = 1 − fb, where fb is fraction bound.
(a) If replacement fluids are administered postfilter, the clearance rate can be estimated using
the following equation:
CVVHpost-dilution = UF x SC (mL/min)
(b) If pre-dilution (i.e., before the filter) fluids are used, clearance across the membrane is
reduced. Clearance can be estimated using the following equation:
CVVHpre-dilution = UF x SC x Qb/(Qb + Qrf)
where Qb is blood flow rate and Qrf is pre-dilution replacement fluid flow rate. For pre-
dilution fluid replacement to affect overall clearance, the rate must be high. Increased
clearance can also occur if both pre- and post-dilution fluids are used.
b. CVVHD
i. Solute removal during CVVHD occurs by passive diffusion. The flow of dialysate is
countercurrent to that of the blood. Movement of solute across the semipermeable membrane
occurs because of a concentration gradient, with movement from an area of higher (blood) to
an area of lower concentration (dialysate). This process occurs until equilibrium is established.
ii. Small substances (e.g., urea with an MW of 60 kDa) are cleared more rapidly than large
substances (e.g., drugs with an MW approaching 500 kDa).
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iii. The ability of a drug to cross the dialysis filter during CVVHD is called the saturation
coefficient (SA). Equations exist for estimating the SA when published data are unavailable. It
can be calculated as SA = CE/Cp, where CE is the concentration in the effluent (spent dialysate)
fluid and Cp is the concentration in plasma. Cp can be calculated as Cp = (CA + CV)/2, where
CA is the concentration drawn from the prefilter port and CV is the concentration drawn
from the postfilter port. This equation can be simplified to SA ~ CE/Cp, but this is slightly less
accurate. CVVHD ~ Qd x SA, where Qd is the dialysate flow rate.
c. Continuous venovenous hemodiafiltration
i. Solute removal during CVVHDF is by diffusion and convection (i.e., both dialysate and
replacement fluids are used).
ii. Clearances of small substances are about equal to the sum of the clearance from CVVH and
CVVHD separately. However, as MW increases, this correlation no longer holds true.
iii. Clearance is estimated as CVVHDF = (UF + Qd) x SA.
d. SLED and EDD
i. As with IHD and CRRT, the most important factor influencing drug removal during SLED/
EDD is protein binding.
ii. Other factors include blood and dialysis flow rates and membrane surface area and flux.
iii. Solute removal during SLED/EDD is greater than that during CVVHD when estimated
over the same time interval because higher dialysis flow rates are used during SLED/EDD
treatments.
e. Drug-Dosing Concepts
i. Drug dosing during CRRT and SLED is often unclear because this information is not included
in product labeling. Manufacturers are not required to study how these therapies alter
clearance.
ii. General dosing considerations for CRRT
(a) For most medications, loading doses require no adjustment.
(b) If a drug is normally cleared by the kidneys or is removed by other RRT modalities,
CRRT will likely have a significant impact on its removal.
(c) When available, drug-specific literature should be used in determining dose and
frequency to minimize the likelihood of dosing errors. Although CRRT is meant to be a
continuous therapy, it is often interrupted. If therapy is held for an extended period, dose
adjustment may be required.
iii. General dosing considerations for SLED
(a) The duration of SLED and its flow rates (dialysate, blood) vary between studies and
institutions, making a general approach to dosing problematic.
(b) In addition, little information is available to guide drug dosing.
(c) Like IHD and CRRT, the most important factors determining drug removal are protein
binding, water solubility, MW (less than 500 kDa), and Vd (less than 0.8 to 1 L/kg).
2-327
Patient Case
Questions 6–8 pertain to the previous case.

F.B. is a 68-year-old, 70 kg , man admitted to your ICU with fever, elevated WBC, respiratory failure requiring
mechanical ventilation, and norepinephrine to support his blood pressure. His medical history is significant for
chronic back pain, for which he takes acetaminophen as needed; diabetes, for which he takes glipizide; and
enalapril for hypertension. Before this admission, he had been otherwise healthy, seeing his primary care provider
about 1 week ago. At that time, his blood pressure was 140/80 mm Hg, and his A1C was 5.2. This laboratory
workup was also unremarkable: WBC 5.0 x 103 cells/mm3, BUN 7 mg/dL, and SCr 0.9 mg/dL. Today, his WBC
is 24 x 103 cells/mm3, BUN 38 mg/dL, and SCr 3.2 mg/dL, with about 325 mL of urine output since his admission
24-hours ago.
It is determined that F.B. needs RRT to manage his volume and control his metabolic derangements. He is
currently on norepinephrine with a mean arterial pressure of 65 mmHg.
6. Which renal replacement mode will most likely be chosen?

A. IHD.
B. Slow-low extended daily dialysis.
C. CRRT.
D. PD.
7. You are asked to dose F.B.’s medications while he is on CRRT. Which propriety has the greatest influence
on drug removal?
A. Protein binding.
B. MW.
C. Vd.
D. Drug charge.
8. F.B. is to start antimicrobial therapy, and you are asked to dose his medications. Which is the most reasonable
approach to determining the appropriate dose and frequency?
A. Look up recommendations for IHD therapy because they are the same as for CRRT.
B. Perform a drug-specific literature search to determine the most appropriate IHD dose, and then use it to
recommend dosing during CRRT.
C. Use only CRRT-based recommendations because drug removal is different between IHD and CRRT.
D. Once a dose and frequency are determined, they can be continued until the patient recovers his renal
function.
2-328
REFERENCES
Measurement of Kidney Function 4. Mehta RL, Kellum JA, Shah SV, et al. Acute
1. Matzke GR, Aronoff GR, Atkinson AJ, et al. Drug Kidney Injury Network: report of an initiative to
dosing considerations in patients with acute and improve outcomes in acute kidney injury. Crit Care
chronic kidney disease—a clinical update from 2007;11:R31. Original report describing how and
Kidney Disease: Improving Global Outcomes why the AKIN staging system was developed.
(KDIGO). Kidney Int. 2011;80:1122-37. In-depth 5. Uchino S, Kellum JA, Bellomo R, et al. Acute renal
discussion of the KDIGO conference to investigate failure in critically ill patients: a multinational,
drug-dosing issues in acute and chronic kidney multicenter study. JAMA 2005;294:813-8. A
disease. Provides a good overview of estimating prospective, observational, multinational study
equations. of ICU patients to determine the prevalence of
2. National Kidney Disease Education Program. Chronic ARF; characterize its etiology, illness severity, and
Kidney Disease and Drug Dosing: Information for clinical practice; and investigate the impact of these
Providers. 2010. Available at http://nkdep.nih.gov/ differences on patient outcomes.
professionals/CKD_DrugDosing_508.pdf. Accessed
February 11, 2015. Provides a recommendation for Renal Replacement Therapies
using either the CG or the MDRD clearance equation 1. Bogard KN, Peterson NT, Plumb TJ, et al. Antibiotic
for adult drug dosing in CKD. dosing during sustained low-efficiency dialysis:
3. Winter MA, Guhr KN, Berg GM. Impact of various special considerations in adult critically ill patients.
body weights on serum creatinine concentrations on Crit Care Med 2011;39:560-70. Addresses issues
the bias and accuracy of the Cockcroft-Gault equa- of antibiotic dosing during SLED and provides an
tion. Pharmacotherapy 2012;32:604-12. This study experience with it.
evaluates the impact of various body weights and 2. Heintz BH, Matzke GR, Dager WE. Antimicrobial
SCr concentrations on the bias and accuracy of CG dosing concepts and recommendations for critically
equation compared with a measured 24-hour CrCl. ill adult patients receiving continuous renal
replacement therapy or intermittent hemodialysis.
Acute Kidney Injury Pharmacotherapy 2009;29:562-77. Provides a
1. Bellomo R, Ronco C, Kellum JA, et al. Acute critical review of current literature related to the
Dialysis Quality Initiative Workgroup. Acute renal influence of CKD and AKI on the pharmacokinetic
failure—definition, outcome measures, animal and pharmacodynamic properties of antimicrobial
models, fluid therapy and information technology agents and suggests dosing strategies for select
needs: the Second International Consensus antimicrobial agents.
Conference of the Acute Dialysis Quality Initiative 3. Tolwani A. Continuous renal-replacement therapy
(ADQI) Group. Crit Care 2004;8:R204-212. for acute kidney injury. N Engl J Med 2012;367:2505-
Original report describing the RIFLE criteria and 14. A good overview of solute clearance during
providing a rational for their conception. CRRT; lists indications and contraindications and
2. Bentley ML, Corwin HL, Dasta J. Drug-induced clinical use.
acute kidney injury in the critically ill adult:
recognition and prevention strategies. Crit Care
Med 2010;38:S169-S174. Provides a good overview
of the mechanisms of drug-induced kidney injury,
recognition of AKI, and AKI prevention.
3. Kidney Disease: Improving Global Outcomes
(KDIGO) Acute Kidney Injury Work Group.
KDIGO clinical practice guideline for acute kidney
injury. Kidney Int Suppl. 2012;2:1-138. Updated
clinical practice guideline for AKI.
2-329
ANSWERS AND EXPLANATIONS TO PATIENT CASES
1. Answer: C IHD become hypotensive and require discontinuation

Reaching a new SCr steady-state concentration requires or a switch to an alternative therapy. Although slow-
several days and is often unpredictable. This is common low extended daily dialysis is an option, some form of
in critically ill patients because the production rate, Vd, continuous renal replacement therapy (CRRT) would
and elimination rate may depend on several factors. likely be chosen because of this patent’s unfavorable
Drug-dosing recommendations do not account for rapid hemodynamics. Continuous renal replacement therapies
changes in renal function, and SCr does not accurately such as CVVH, CVVHD, and CVVHDF are often used
estimate CrCl. Although in 2005 the National Institute of because they allow for slower flow rates and improved
Standards and Technology released materials traceable hemodynamics. However, there is no clear benefit with
to a reference for Cr, this reference does not account one therapy over another.
for acute changes but only tries to standardize the
measurement. 7. Answer: A
The greatest influence of drug removal during CRRT is
2. Answer: C binding to albumin (i.e., the higher the percent bound,
In 2010, the National Kidney Disease Education Program the less drug removed). The MW of most drugs has little
recommended that an adult’s drug dosing be based on impact on the drug’s overall clearance because most
either the MDRD study equation or CrCl using the CG drugs are less than 500 kDa. Continuous venovenous
equation. Although the CKD-EPI equation is gaining hemofiltration can effectively remove drugs with an
acceptance it has not been adequately validated in the MW less than 15,000 kDa, whereas the greatest impact
elderly or in African Americans with higher GFR’s. of removal during CVVHD occurs with drugs having
an MW less than 500 kDa. Because CRRT is performed
3. Answer: C using slower flow rates, time is allowed for the drugs to
Both RIFLE class “F” and AKIN stage 3 are met using equilibrate between body compartments, making Vd less
similar SCr and urine output criteria. For this case, the of an issue. Although not well studied, binding to the
SCr increased by at least 3-fold above baseline, and the filter is not important for most drugs.
patient’s urine output was less than 0.3 mL/kg/hour for
24 hours. 8. Answer: C
Continuous renal replacement therapy presents
4. Answer: A unique challenges, and dosing considerations are not
F.B. has at least severe sepsis that lead to decreased renal interchangeable between intermittent and continuous
perfusion causing AKI. Enalapril likely contributed therapies. In general, if a drug is normally cleared by the
to the injury by altering renal hemodynamics. Both kidneys or is removed by other RRT modalities, CRRT
glipizide and acetaminophen are unlikely to cause AKI. will likely have a significant impact on its clearance. In
the absence of significant protein binding, removal can
5. Answer: A be expected. Drug-specific guidance can be obtained
Acute kidney injury cannot be diagnosed with a specific from the primary literature or from summary charts, but
test or study. The patient’s rate of kidney loss, symptoms, it should be reviewed with caution because flow rates
and coexisting diseases are very important because these during CRRT may vary. Although CRRT is meant to be a
may lead to the cause of injury. Drug-induced AKI is continuous therapy, it is often interrupted, and drug dose
most common in the setting of additional insults and and frequency may need adjustment.
may occur even after the drug is discontinued.
6. Answer: C
Intermittent hemodialysis (IHD) is often used in critically
ill patients because many physicians are familiar with
this therapy; however, about 20%–30% of patients on
2-330
ANSWERS AND EXPLANATIONS TO SELF-ASSESSMENT QUESTIONS
1. Answer: B 5. Answer: C
The CG equation has historically been used to estimate AKIN stage 3 is met, regardless of the patient’s change
CrCl. Several patient factors may influence results in SCr or urine output, because he is receiving RRT.
(i.e., measured SCr, age, weight, and sex). For patients
who are obese, using total body weight will likely 6. Answer: A
overestimate CrCl. Although not universally accepted, Solute removal during CVVH is by convection, which is
using an adjusted weight (with a factor of 0.4) is more primarily influenced by membrane pore size, free fraction
accurate, compared with a measured 24-hour CrCl, than of drug, and ultrafiltration rate. Clearance is increased as
actual or ideal body weight in this patient group. Only fluid moves across the filter, “pulling” solute with it.
since 2005 has the National Institute of Standards and
Technology released materials traceable to a reference 7. Answer: C
for Cr, using isotope dilution mass spectroscopy, in an Drug-dosing recommendations for IHD can be found
attempt to standardize measured SCr. in many resources. However, dosing during CRRT and
SLED is less clear. Primary literature and/or summary
2. Answer: A tables for CRRT and SLED should be referenced because
The MDRD study equation was developed from a these recommendations are not usually found in other
sample of patients with CKD using a urinary clearance sources. Use caution to ensure that identical modes of
of 125I iothalamate. It has been validated in white and CRRT are referenced with similar flow rates.
African American patients between 18 and 70 years of
age with reduced renal function. Compared with CG 8. Answer: A
and measured CrCl from a 24-hour urine collection, Although protein binding, MW, Vd, and drug charge
MDRD has been shown to provide a better estimate of may influence removal, binding to plasma protein has
clearance, but additional studies are needed. The MDRD the greatest impact because only unbound drugs can be
study equation underestimates the measured GFR when cleared through the filter.
greater than 60 mL/minute per 1.73m2, and it should be
used only when the SCr level is stable.
3. Answer: D
The CKD-EPI equation uses the same four variables
(SCr, age, sex, and race) as the MDRD study equation
for predicting the GFR in adults 18 years or older. The
CKD-EPI equation has been shown to be more accurate
than the MDRD equation when the GFR is greater than
60 mL/minute per 1.73m2. However, CKD-EPI should
be used with caution in patients with non–steady-state Cr
production and elimination.
4. Answer: B
Although AIN is an uncommon occurrence, drugs are
associated with more than 75% of cases if it occurs.
Several medications have been associated with AIN,
including antimicrobials (e.g.,penicillins, cephalosporins,
sulfonamides, ciprofloxacin, vancomycin, macrolides)
and histamine-2 receptor antagonists.
2-331

ccpc15 Principles Renal Clearance Acute Kidney Renal Replacement Workbook

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ccpc15 Principles Renal Clearance Acute Kidney Renal Replacement Workbook

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Principles of Estimating Renal

Clearance, Acute Kidney Injury,

Principles of Estimating Renal

Learning Objectives RRT Renal replacement therapy

4. Through which mechanism is ceftriaxone most

5. Using the AKIN staging, which best describes the

6. Which best describes the principle for clearance

I. MEASUREMENT OF KIDNEY FUNCTION

B. Limitations to Using SCr for Estimating GFR

C. Estimating CrCl (Table 1)

Table 1. Common Equations for Estimating GFR

MDRD (four-variable) study equation

MDRD (four-variable) study equation using IDMS SCr

D. Considerations for Drug Dosing

II. ACUTE KIDNEY INJURY

B. Definitions (Table 2a and 2b)

Table 2a. Criteria for AKI

Table 2b. Criteria for AKI

c. Medications known to cause tubular obstruction include acyclovir, methotrexate, sulfadiazine,

Questions 3–5 pertain to the following case.

3. Which best describes F.B.’s AKI?

4. Which medication is most likely contributing to his AKI?

III. RENAL REPLACEMENT THERAPIES

A. General Approaches to Managing AKI

B. Mode of Renal Replacement for AKI

D. Continuous Renal Replacement Therapies

G. CRRT and Drug-Dosing Concepts

CVVHpre-dilution = UF x SC x Qb/(Qb + Qrf)

Questions 6–8 pertain to the previous case.

6. Which renal replacement mode will most likely be chosen?

ANSWERS AND EXPLANATIONS TO PATIENT CASES

1. Answer: C IHD become hypotensive and require discontinuation

ANSWERS AND EXPLANATIONS TO SELF-ASSESSMENT QUESTIONS

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