Effect of captopril on progression to clinical proteinuria in patients with insulin-dependent diabetes mellitus and microalbuminuria. European Microalbuminuria Captopril Study Group

Abstract

Objectives: To study the effect of angiotensin converting enzyme inhibition on the rate of progression to clinical proteinuria and the rate of change of albumin excretion rates in patients with insulin-dependent diabetes mellitus and persistent microalbuminuria.

Design and setting: Randomized, double-blind, placebo-controlled clinical trial of 2 years' duration at 12 hospital-based diabetes centers.

Patients: Ninety-two patients with insulin-dependent diabetes mellitus and persistent microalbuminuria but no hypertension.

Intervention: The patients were randomly allocated in blocks of two to receive either captopril, 50 mg, or placebo twice per day.

Measurements: Albumin excretion rate, blood pressure, glycosylated hemoglobin level, and fructosamine level every 3 months; urinary urea nitrogen excretion every 6 months; and glomerular filtration rate every 12 months.

Results: Twelve patients receiving placebo and four receiving captopril progressed to clinical proteinuria, defined as an albumin excretion rate persistently greater than 200 micrograms/min and at least a 30% increase from baseline (P = .05). The probability of progression to clinical proteinuria was significantly reduced by captopril therapy (P = .03 by log-rank test). Albumin excretion rate rose from a geometric mean (95% confidence interval) of 52 (39 to 68) to 76 (47 to 122) micrograms/min in the placebo group but fell from 52 (41 to 65) to 41 (28 to 60) micrograms/min in the captopril group, a significant difference (P < .01). Mean blood pressure was similar at baseline in the two groups and remained unchanged in the placebo group but fell significantly, by 3 to 7 mm Hg, in the captopril group. Glycosylated hemoglobin levels and glomerular filtration rate remained stable in the two groups.

Conclusions: Captopril therapy significantly impeded progression to clinical proteinuria and prevented the increase in albumin excretion rate in nonhypertensive patients with insulin-dependent diabetes mellitus and persistent microalbuminuria.