Effective postponement of diabetic nephropathy with enalapril in normotensive type 2 diabetic patients with microalbuminuria

OBJECTIVE - This study determines the long-term efficacy of the ACE inhibitor, enalapril, in reducing the progression of microalbuminuria to clinical albuminuria in normotensive patients with type 2 diabetes. RESEARCH DESIGN AND METHODS - There were 103 normotensive type 2 diabetic patients with persistent albumin excretion rate (AER) 20-200 mu g/min and normal renal function followed for 5 years in a prospective randomized single-blind placebo-controlled trial. AER, blood pressure, fasting plasma glucose, and HbA(1) were measured every 3-4 months and glomerular filtration rate (GFR), renal plasma flow (RPF), and urinary urea every 12 months. RESULTS - In the patients treated with enalapril, AER decreased from 55 +/- 33 to 20 +/- 59 mu g/min (geometric mean +/- SD), whereas in the placebo group, AER increased from 53 +/- 31 to 85 +/- 90 mu g/min after 5 years. Within 5 years, 7.7% (4/52) of enalapril-treated subjects and 23.5% (12/51) of placebo-treated subjects progressed to clinical albuminuria defined as AER >200 mu g/min and at least 34% above baseline (risk reduction = 66.7%, P < 0.001). AER increased at an annual rate of 12.3% (95% CI 9.8-14.9) in the placebo group, while it declined by 16.7% (95% CI - 18.3 to - 15.2) in the enalapril group (P < 0.001). In addition, 8 of the 12 placebo-treated patients had evidence of coronary artery disease. The rest of the parameters remained practically unchanged in the two groups. CONCLUSIONS - After 5 years of therapy with enalapril, compared with placebo, normotensive subjects with type 2 diabetes experienced significantly less progression of microalbuminuria to clinical albuminuria, reduced AER, and preserved GFR.