Diabetic nephropathy, the leading cause of end-stage renal disease (ESRD) in the United States, affects 20% to 30% of patients with diabetes.1 Early diagnosis and aggressive treatment may delay the progression of kidney disease.
Here we address questions that often arise in the management of diabetic kidney disease in the primary care setting, such as:
- What is the next step when an elevated albumin-creatinine ratio is detected?
- Which tests are recommended for monitoring the progression of diabetic nephropathy?
- When should patients be referred to a nephrologist?
We review screening and monitoring tests, discuss the workup of nondiabetic causes of albuminuria, and describe interventions that can slow or prevent the progression of renal disease. The Algorithm provides an overview of the management of diabetic nephropathy.
Annual screening for nephropathy is recommended in patients with diabetes who have no history of kidney disease.1-3 Screening is initiated when type 2 diabetes is diagnosed because the onset of this disease often precedes the clinical diagnosis by 10 years; the onset of type 1 diabetes precedes the clinical diagnosis by 5 years.1-3
Microalbuminuria, or incipient diabetic nephropathy, is the earliest sign of diabetic renal disease.3 Microalbuminuria is defined as an albumin-creatinine ratio between 30 and 300 µg/mg. Macroalbuminuria, or overt nephropathy, is defined as an albumin-creatinine ratio higher than 300 µg/mg. These values correlate with the amount of albumin excreted per day (300 µg/mg = 300 mg albumin/24 hours).
Albuminuria (albumin-creatinine ratio greater than 300 µg/mg) is an established risk factor for cardiovascular mortality1,3 and a sign of progression to ESRD.2,3 Eighty percent of patients with type 1 diabetes with microalbuminuria will progress to overt nephropathy in the absence of intervention.3 Overt nephropathy will develop in 50% of those patients in 10 years and in more than 75% by 20 years. Without treatment, 20% to 40% of patients with type 2 diabetes who have microalbuminuria progress to overt nephropathy and about 20% of those will progress to ESRD.3
Screening methods. The preferred method is measurement of the albumin-creatinine ratio in a random spot collection (normal values, less than 30 µg/mg). First morning voids or morning collections are most accurate, but voids at other times of the dayare acceptable.3
Another screening option is timed urine collection for albumin or total protein. However, because of frequent errors in collection, the difficulty of collection, and the accuracy and convenience of the albumin-creatinine ratio, this test is not often used.
The standard urine dipstick, which primarily detects albumin, is too insensitive for microalbuminuria screening because results become positive only after albumin levels exceed 300 mg/d.4 Semiquantitative urine albumin dipsticks may be used for screening for macroalbuminuria if urinary microalbumin measurement is not available.Note, however, that proteinuria in the absence of albuminuria is an important clue to the presence of paraproteinuria and warrants performance of urine and serum protein electrophoresis. Thus, both urine albumin and total protein should be assessed in select patients.
Increasing values in the normal range indicate progression to nephropathy.1 If results are higher than 30 µg/mg, repeated testing is required before the diagnosis of diabetic nephropathy is made. False-positive results may be caused by exercise, urinary tract infection, congestive heart failure, and fever. Patients should not be screened after heavy exertion or during an acute illness. Two elevated results of 3 measurements over a 3- to 6-month period support the diagnosis of diabetic nephropathy.
Another useful parameter in screening for kidney disease and monitoring disease progression is measurement of serum creatinine to estimate the glomerular filtration rate (GFR). GFR can decline without accompanying albuminuria in a substantial number of patients.1,5,6 Monitor GFR every 6 months in patients with kidney disease2 and every 12 months in those with no disease.1,2 There are convenient online calculators (eg, at www.nephron.com) that use the modification of diet in renal disease (MDRD) equation to estimate GFR.
Stages of renal disease. Five stages of kidney disease have been defined by the National Kidney Foundation's Kidney Disease Outcome Quality Initiative (Table).7 The grading system assists in patient education and communication with specialists.
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- Effects of ramipril on cardiovascular and microvascular outcomes in people with diabetes mellitus: results of the HOPE study and MICRO-HOPE substudy. Heart Outcomes Prevention Evaluation (HOPE) Study Investigators. Lancet. 2000;355:253-259.
- Lewis EJ, Hunsicker LG, Clarke WR, et al. Renoprotective effect of the angiotensin-receptor antagonist irbesartan in patients with nephropathy due to type 2 diabetes. N Engl J Med. 2001;345:851-860.
- Veterans Health Administration and Dept of Defense. Management of diabetes mellitus in primary care. Clinical practice guideline. 2003. Available at: www.oqp.med.va.gov/cpg/DM/DM3_cpg/content/introduction.htm. Accessed on April 20, 2006.