CONTRASTING EFFECTS OF ANGIOTENSIN-CONVERTING INHIBITOR AND ALPHA-1-ANTAGONIST ON ALBUMINURIA IN INSULIN-DEPENDENT DIABETES-MELLITUS PATIENTS WITH NEPHROPATHY

Objective. The main aim of this study was to examine the effects of an angiotensin converting inhibitor, enalapril, and an alpha-1 (alpha-1) antagonist, doxazosin, on albumin excretion, renal haemodynamics and tubular function in insulin-dependent diabetes mellitus patients with nephropathy. Design. The study consisted of a four-week run-in period, a four-week active treatment period, a four-week wash-out period and a second four-week active treatment period. Setting. The study was per formed in the out-patient clinic at a university hospital. Subjects. T en patients with insulin dependent diabetes mellitus with macroarbumin uria (> 200 mu g min(-1)), mild to moderate hypertension (diastolic br ood pressure 85-115 mmHg) and serum creatinine level below 200 mu mol L(-1) were included in the study. Main outcome measures. The effect of the drugs on albumin and total protein excretion, beta-2-microglobuli n, proximal tubular enzyme markers and renal haemodynamics. Results. S ystolic and diastolic blood pressure were equally reduced by both drug s. Enalapril reduced albumin excretion from 1090 +/- 281 mu g min(-1) to 742 +/- 246 mu g min(-1) (P < 0.01) and total protein excretion fro m 2.0 +/- 0.4 g per 24 h to 1.3 +/- 0.4 per 24 h whereas doxazosin was without effect. Glomerular filtration rate and effective renal plasma flow were unchanged by either drug. Doxazosin increased filtration fr action from 0.21 +/- 0.02 to 0.23 +/- 0.01 (P < 0.05). The urinary exc retion of the proximal enzyme markers N-acetyl-beta-glucosaminidase an d alkaline phosphatase were elevated as well as urinary excretion of b eta-2-microglobulin. However, neither the excretion of beta-2-microglo bulin nor the enzyme markers were affected by either drug. Conclusions . Enalapril, but not doxazosin, reduces albuminuria in insulin depende nt diabetes mellitus patients with nephropathy. The drugs exert differ ential effects on renal haemodynamics.