Effect of Angiotensin-Converting Enzyme Inhibition on Renal Function and Albuminuria in Normotensive Type I Diabetic Patients

Normotensive patients with insulin-dependent (type l) diabetes mellitus (n = 18) were given 25 mg captopril (b.i.d.) and placebo for 3 mo in a randomized double-blind crossover study. Patients had normal renal function, and none had retinopathy. Albuminuria was <20 μg/min in 12 patients and between 20 and 200 μg/min in the other 6. Patients were examined at the end of the placebo and captopril phases. Captopril caused little reduction in blood pressure obtainedby 24-h ambulatory monitoring (systolic 126.0 ± 2.7 to 123.9 ± 2.4 mmHg, P< 0.08; diastolic 74.2 ± 1.9 to 72.1 ± 1.9 mmHg, P < 0.09). Captopril lowered glomerular filtration rate from 99.5 ± 7.7 to 71.0 ± 5.5 ml · min⁻¹ · 1.73 m⁻²(P < 0.01), whereas renal plasma flow (443.9 ± 15.2 ml.min⁻¹. 1.73 m⁻²) remained unchanged. Filtration fraction was reduced from 22.4 ± 1.4 to 17.4 ± 1.4% (P < 0.01). Urinary albumin excretion was reduced from 59.1 ± 0.15 to 27.7 ± 13.9 μg/min (P < 0.1). Reduction was relatedto the extent of initial albuminuria (r = 0.997, P < 0.001), a relationship that remained significant after logarithmic transformation (r = 0.540, P < 0.02). Dextran clearance was used to determine glomerular capillary function. Angiotensin inhibition caused reduction in effective glomerular pore size and also reduced flow via the nondiscriminatory shunt. Angiotensin inhibition in normotensive patients with type I diabetes was well tolerated. Reduction in albuminuria is mediated by a combination of hemodynamic changes and alterations in glomerular capillary function.