Contrasting effects of angiotensin converting inhibitor and alpha‐1‐antagonist on albuminuria in insulin‐dependent diabetes mellitus patients with nephropathy

Abstract

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. 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. The study was performed in the out-patient clinic at a university hospital. 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. The effect of the drugs on albumin and total protein excretion, beta-2-microglobulin, proximal tubular enzyme markers and renal haemodynamics. 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. Enalapril, but not doxazosin, reduces albuminuria in insulin dependent diabetes mellitus patients with nephropathy. The drugs exert differential effects on renal haemodynamics.