Effective Postponement of Diabetic Nephropathy With Enalapril in Normotensive Type 2 Diabetic Patients With Microalbuminuria

Abstract

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 micrograms/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 HbA1 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 micrograms/min (geometric mean ± SD), whereas in the placebo group, AER increased from 53 ± 31 to 85 ± 90 micrograms/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 micrograms/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.