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Contrasting effects of angiotensin converting inhibitor and alpha-1-antagonist on albuminuria in insulin-dependent diabetes mellitus patients with nephropathy
Authors:H. HOLDAAS  A. HARTMANN  K.J. BERG  H. LANGBERG  L. BLYSTAD  P. FAUCHALD
Abstract:Abstract. Objective . The main aim of this study was to examine the effects of an angiotensin converting inhibitor, enalapril, and an alpha-1 (α-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 μg min?1), mild to moderate hypertension (diastolic blood pressure 85–115 mmHg) and serum creatinine level below 200 μmol L?1 were included in the study. Main outcome measures . The effect of the drugs on albumin and total protein excretion, β-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 μg min?1 to 742 ± 246 μg 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 β-2-microglobulin. However, neither the excretion of β-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.
Keywords:albuminuria  diabetes mellitus  angiotensin converting inhibitor  alpha-1-antagonist  renal haemodynamics  tubular function
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