Patient Information Handout: Am Fam Physician

Diabetic Nephropathy: Common Questions
MICAH L. THORP, D.O., M.P.H, Lake Road Nephrology Clinic, Milwaukie, Oregon.
Am Fam Physician.�2005�Jul�1;72(01):96-99.
� Patient Information Handout
Diabetic nephropathy, or diabetic kidney disease, affects 20 to 30 percent of patients

with diabetes. It is a common cause of kidney failure. Diabetic nephropathy presents in
its earliest stage with low levels of albumin (microalbuminuria) in the urine. The most
practical method of screening for microalbuminuria is to assess the albumin-to-
creatinine ratio with a spot urine test. Results of two of three tests for microalbuminuria
should be more than 30 mg per day or 20 mcg per minute in a three- to six-month
period to diagnose a patient with diabetic nephropathy. Slowing the progression of
diabetic nephropathy can be achieved by optimizing blood pressure (130/80 mm Hg or
less) and glycemic control, and by prescribing an angiotensin-converting enzyme
inhibitor or angiotensin receptor blocker. Patients with diabetes and isolated
microalbuminuria or hypertension benefit from angiotensin-converting enzyme inhibitors
or angiotensin receptor blockers. In the event that these medications cannot be
prescribed, a nondihydropyridine calcium channel blocker may be considered. Serum
creatinine and potassium levels should be monitored carefully for patients receiving
angiotensin-converting enzyme inhibitors or angiotensin receptor blockers. These
medications should be stopped if hyperkalemia is pronounced.
Approximately one fourth to one third of patients with diabetes develop renal
manifestations. Because of the large prevalence of diabetes in the general population,
diabetes has become the leading cause of end-stage renal disease in the United
States.1 There is good evidence that early treatment delays or prevents the onset of
diabetic nephropathy, or diabetic kidney disease. A variety of issues and specific
questions often arise in the management of diabetic nephropathy. This article
addresses some of the common questions raised by physicians managing patients with
this disease.
Diagnosis of Diabetes with Renal Manifestations

Diabetic nephropathy presents in its earliest stage with low levels of albumin
(microalbuminuria) in the urine. This often is referred to as incipient nephropathy. As the
disease progresses, urine albumin levels increase until the patient develops overt
nephropathy (defined as more than 300 mg per 24 hours or more than 200 mcg per
minute). Overt nephropathy often occurs in conjunction with a hyperfiltrative period, in
which the creatinine clearance and glomerular filtration rate are high. The elevated
clearance is deceptive, however, because it is followed by a gradual decrease in
glomerular filtration rate that ultimately leads to kidney failure.2
Microalbuminuria rarely develops in patients with type 1 diabetes during the first few
years of the disease. For this reason, the American Diabetes Association (ADA)
recommends that screening begin only after the patient has had type 1 diabetes for five
years.3
Because of the long duration of abnormal glucose metabolism that often precedes
diagnosis, patients with type 2 diabetes are more likely to have microalbuminuria (or
overt nephropathy) at diagnosis. Thus, patients with type 2 diabetes should be screened
at the time of diagnosis for the presence of microalbuminuria.3
Screening for microalbuminuria can be accomplished in a variety of ways. The three

approaches most commonly used are measurement of albumin-to-creatinine ratio on a
spot urine test, albumin from a 24-hour urine collection, and albumin from a timed
collection (e.g., 10 hours overnight). The ratio from spot urine is obtained most easily,
and collection errors occur less frequently. A ratio of more than 30 mg albumin per 1 g
creatinine is considered elevated on a spot urine test. Urinary albumin of more than 30
mg per 24 hours is diagnostic on a timed sample. Transient elevations of
microalbuminuria can be caused by exercise, urinary tract infections, hyperglycemia,
febrile illness, severe hypertension, or heart failure. Abnormal results should be
confirmed with repeated testing. The ADA guidelines suggest that two of three tests for
microalbuminuria need to be positive in a three- to six-month period to diagnose
diabetic nephropathy correctly.3
Patients with overt nephropathy do not need screening for microalbuminuria because
the level of protein in the urine is high enough to be detected easily on routine
urinalysis.
Definitive Treatment of Diabetic Nephropathy
As with most complications of diabetes, there is no definitive “cure” for diabetic

nephropathy. However, a recent study4 followed nearly 400 patients with type 1
diabetes and micro-albuminuria for six years, and more than one half of the patients in
the study experienced regression of microalbuminuria. This suggests that not all
patients with microalbuminuria progress to diabetic nephropathy. Patients with low
systolic blood pressure, low levels of cholesterol, and low levels of glycosylated
hemoglobin were more likely to experience regression.
Management of Diabetes with Renal Disease
Slowing the progression of diabetic nephropathy includes optimizing glycemic

control (as demonstrated by the United Kingdom Prospective Diabetes Study5 [UKPDS]
and the Diabetes Control and Complications Trial6), controlling hypertension, and using
angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers
(ARBs). More controversial interventions include the use of a protein-restricted diet for
patients with type 1 diabetes7 and nondihydropyridine calcium channel blockers in the
event that ACE inhibitors or ARBs cannot be used for patients with microalbuminuria or
nephropathy. Dihydropyridine calcium channel blockers are not effective.3
On the basis of the trials mentioned above, hemoglobin A1C levels should be kept at
less than 7 percent.8Ideal blood pressure measurements are unclear, but on the basis
of the UKPDS5 and Hypertension Optimal Treatment studies,9 a reasonable blood
pressure target is 130/80 mm Hg or less. The Joint National Committee on Prevention,
Detection, Evaluation, and Treatment of High Blood Pressure recommends this
target,10 as does the National Kidney Foundation.11 There is much evidence to show that
ACE inhibitors slow the progression of diabetic nephropathy in patients with type 1
diabetes,12,13 and some evidence that the progression is slowed in patients with type 2
diabetes exists as well.14 Results of the Reduction of Endpoints in NIDDM (non–insulin-
dependent diabetes mellitus) with the Angiotensin II Antagonist Losartan study15 and the
Irbesartan Diabetic Nephropathy Trial16 showed that ARBs slow the progression of
diabetic nephropathy significantly in patients with type 2 diabetes. If one class cannot be
tolerated, the other may be substituted.8
Prescribing ACE Inhibitors or ARBs
NORMOTENSIVE WITH MICROALBUMINURIA OR HYPERTENSIVE WITHOUT

MICROALBUMINURIA
Studies have shown that ACE inhibitors and ARBs are beneficial in reducing the
progression of microalbuminuria in normotensive patients with type 1 diabetes17 and in
normotensive patients with type 2 diabetes.3,18
Patients with hypertension and diabetes clearly benefit from lowering of blood pressure,
regardless of the presence of nephropathy. A number of studies suggest that a variety
of agents may be appropriate first-line treatments for blood pressure. Because ACE
inhibitors and ARBs have been shown to decrease or slow the progression of
complications in diabetes, it seems reasonable to use a medication from one of these
two classes of antihypertensive drugs as a first-line agent in hypertensive patients who
have diabetes without microalbuminuria.8,14,19
ELEVATED SERUM CREATININE

There is no specific creatinine level beyond which ACE inhibitors or ARBs cannot be
used. Patients with more advanced nephropathy may experience greater benefits from
these medications than patients with mild nephropathy.
A review20 of 12 randomized clinical trials evaluating renal disease progression in

patients with preexisting renal insufficiency found a strong association between acute
increases in serum creatinine levels of up to 30 percent that stabilize within the first two
months of ACE inhibitor therapy and long-term preservation of kidney function.
With this in mind, patients who initiate ACE inhibitor (and presumably ARB) therapy
should have creatinine levels checked shortly after starting the medication, and serum
potassium levels should be monitored for hyperkalemia while the patient receives the
medication.19
Other Antihypertensive Choices
A number of small studies21 have demonstrated that nondihydropyridine calcium

channel blockers can reduce albuminuria. These studies fail to show a reduction in the
rate of decrease of glomerular filtration rate with their use.
References: http://www.aafp.org/afp/2005/0701/p96.html

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Diabetic Nephropathy: Common Questions

� Patient Information Handout

Diabetic nephropathy, or diabetic kidney disease, affects 20 to 30 percent of patients

Diagnosis of Diabetes with Renal Manifestations

Screening for microalbuminuria can be accomplished in a variety of ways. The three

Definitive Treatment of Diabetic Nephropathy

As with most complications of diabetes, there is no definitive “cure” for diabetic

Management of Diabetes with Renal Disease

Slowing the progression of diabetic nephropathy includes optimizing glycemic

Prescribing ACE Inhibitors or ARBs

NORMOTENSIVE WITH MICROALBUMINURIA OR HYPERTENSIVE WITHOUT

ELEVATED SERUM CREATININE

A review20 of 12 randomized clinical trials evaluating renal disease progression in

Other Antihypertensive Choices

A number of small studies21 have demonstrated that nondihydropyridine calcium

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