The aim of our prospective study was to evaluate putative progression promoters, kidney function, and prognosis during long-term treatment with angiotensin-converting enzyme inhibition in insulin-dependent diabetes mellitus patients suffering from diabetic nephropathy. Eighteen consecutive hypertensive insulin-dependent diabetes patients with nephropathy (mean age, 33 years) who had not been treated previously were all treated with captopril in combination with frusemide or bendrofluazide. The four patients who were refractory to this regimen also received nifedipine. Treatment was continued for a median of 8.9 years (range, 6.3 to 9.8, years). Renal function was assessed every 6 months by measurement of glomerular filtration rate (GFR) (single-bolus 51Cr-EDTA technique) and albuminuria by radioimmunoassay. Baseline values (+/- SE) were mean arterial blood pressure 146/93 +/- 3/1 mm Hg, albuminuria (geometric mean +/- antilog SE) 982 +/- 1.2 micrograms/min, and GFR 98 +/- 5 mL/min/1.73 m2. Angiotensin-converting enzyme inhibition induced a significant reduction during the whole treatment period of blood pressure (137/85 +/- 3/1 mm Hg; P < 0.01) and albuminuria (392 +/- 1.4 microns/min; P < 0.01), and the rate of decline in GFR was 4.4 +/- 0.7 mL/min/yr, in contrast to previous reports of 10 to 14 mL/min/yr (natural history). Univariate analysis revealed a significant correlation between the rate of decline in GFR and mean arterial blood pressure (r = 0.58, P = 0.01), albuminuria (r = 0.67, P < 0.01), hemoglobin A1c (r = 0.69, P < 0.01), and serum total cholesterol concentration (r = 0.51, P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)