This Journal feature begins with a case vignette highlighting a common clinical problem. Evidence supporting various strategies is then presented, followed by a review of formal guidelines, when they exist. The article ends with the authors’ clinical recommendations.
N EPHROPATHY IN P ATIENTS WITH T YPE 2 D IABETES
GIUSEPPE REMUZZI, M.D.,ARRIGO SCHIEPPATI, M.D., AND PIERO RUGGENENTI, M.D.
ute), or overt nephropathy, occurs in 20 to 40 percent of patients over a period of 15 to 20 years after the onset of diabetes. Once macroalbuminuria is present, creatinine clearance declines at a rate that varies widely from patient to patient; the average reduction is 10 to 12 ml per minute per year in untreated patients.4,5 Hypertensionand proteinuria may accelerate the decline in the glomerular filtration rate and the progression to end-stage renal disease.
STRATEGIES AND EVIDENCE
Screening for Microalbuminuria
A 60-year-old man was found to have type 2 diabetes mellitus two months ago. He has a serum creatinine level of 1.5 mg per deciliter (133 µmol per liter); a dipstick test shows proteinuria (++). His systolic bloodpressure is 150 mm Hg, and his diastolic pressure is 90 mm Hg. He smokes half a pack of cigarettes daily. What can be done to reduce his risk of progressive renal disease?
THE CLINICAL PROBLEM
Nephropathy associated with type 2 diabetes is the most frequent cause of end-stage renal disease in the United States, Europe, and Japan. In the United States, the incidence of diabetic nephropathy hasincreased by 150 percent in the past 10 years, a trend also seen in Europe.1,2 In North America, 40 percent of patients starting dialysis in 1998 had diabetic nephropathy. Among patients who require dialysis, those with diabetes have a 22 percent higher mortality at one year and a 15 percent higher mortality at five years than patients without diabetes. In 1998, the estimated cost of care for adiabetic patient undergoing dialysis was $51,000 per year, which was about $12,000 more than the cost for a nondiabetic patient.1 The first sign of renal involvement in patients with type 2 diabetes is most often microalbuminuria (urinary albumin excretion, 20 to 200 µg per minute in an overnight urine sample), which is classified as incipient nephropathy (Table 1).3 Microalbuminuria affects 20 to 40percent of patients 10 to 15 years after the onset of diabetes. Progression to macroalbuminuria (urinary albumin excretion, >200 µg per minFrom the Unit of Nephrology, Ospedali Riuniti di Bergamo; and the Clinical Research Center for Rare Diseases, Mario Negri Institute for Pharmacological Research — both in Bergamo, Italy. Address reprint requests to Dr. Schieppati at Mario Negri Institute, ViaGavazzeni 11, 24100 Bergamo, Italy.
Early recognition of renal changes increases the chance to prevent the progression from incipient to overt nephropathy. A routine dipstick urinalysis should be performed at the time of diagnosis, because of the difficulty in precisely dating the onset of type 2 diabetes. If the test is positive for protein, analysis of a 24-hour urine sample is recommended forquantification of urinary protein excretion (Fig. 1). Since a negative dipstick test for protein does not rule out microalbuminuria, a more sensitive method should be used (e.g., the Micral test or radioimmunoassay for albumin) and repeated every year, if the result is negative. If the result is positive, microalbuminuria can be confirmed and quantified by measuring the ratio of albumin tocreatinine in a morning urine sample or by measuring the rate of albumin excretion in a 24hour or overnight urine sample. Overnight samples can be used to distinguish true microalbuminuria from postural or exercise proteinuria, which are common in young patients. Isolated microalbuminuria or macroalbuminuria usually indicates the presence of diabetic nephropathy, but the presence of other abnormalities...