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 performed in the out-patient clinic at a university hospital. SUBJECTS: Ten patients with insulin dependent diabetes mellitus with macroalbuminuria (> 200 micrograms min-1), mild to moderate hypertension (diastolic blood pressure 85-115 mmHg) and serum creatinine level below 200 mumol L-1 were included in the study. MAIN OUTCOME MEASURES: The effect of the drugs on albumin and total protein excretion, beta-2-microglobulin, proximal tubular enzyme markers and renal haemodynamics. RESULTS: Systolic and diastolic blood pressure were equally reduced by both drugs. Enalapril reduced albumin excretion from 1090 +/- 281 micrograms min-1 to 742 +/- 246 micrograms min-1 (P < 0.01) and total protein excretion from 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 fraction from 0.21 +/- 0.02 to 0.23 +/- 0.01 (P < 0.05). The urinary excretion of the proximal enzyme markers N-acetyl-beta-glucosaminidase and alkaline phosphatase were elevated as well as urinary excretion of beta-2-microglobulin. However, neither the excretion of beta-2-microglobulin nor the enzyme markers were affected by either drug. CONCLUSIONS: Enalapril, but not doxazosin, reduces albuminuria in insulin dependent diabetes mellitus patients with nephropathy. The drugs exert differential effects on renal haemodynamics.