Comparison of reduction in microalbuminuria by enalapril and hydrochlorothiazide in normotensive patients with insulin dependent diabetes.

OBJECTIVE To compare the effects of sodium depletion and of angiotensin I converting enzyme inhibition on microalbuminuria in insulin dependent diabetes. DESIGN Randomised, double blind, double dummy parallel study of normotensive diabetic patients with persistent microalbuminuria (30-300 mg/24 h) treated with enalapril or hydrochlorothiazide for one year after a three month, single blind placebo period. SETTING Diabetic clinic in a tertiary referral centre. PATIENTS 10 diabetic patients with low microalbuminuria (30-99 mg/24 h) and 11 with high microalbuminuria (100-300 mg/24 h). INTERVENTIONS 11 subjects (six with low microalbuminuria, five with high microalbuminuria) were given enalapril 20 mg plus placebo hydrochlorothiazide once daily and 10 (four with low microalbuminuria, six with high microalbuminuria) hydrochlorothiazide 25 mg plus placebo enalapril once daily. MAIN OUTCOME MEASURES Monthly assessment of urinary albumin excretion and mean arterial pressure; plasma active renin and aldosterone concentrations and renal function studies at 0, 6, and 12 months. RESULTS Median urinary albumin excretion decreased from 59 (range 37-260) to 38 (14-146) mg/24 h with enalapril and from 111 (33-282) to 109 (33-262) mg/24 h with hydrochlorothiazide (analysis of variance, p = 0.0436). During the last three months of treatment with enalapril five patients had persistent normoalbuminuria (2-3 times below 30 mg/24 h), five low microalbuminuria, and one high microalbuminuria; in the hydrochlorothiazide group one had normoalbuminuria, three low microalbuminuria, and six high microalbuminuria (chi 2 test = 6.7; p = 0.03). Mean arterial pressure did not differ before (98 (SD 7) with enalapril v 97 (9) mm Hg with hydrochlorothiazide) or during treatment (88 (7) with enalapril v 90 (7) mm Hg with hydrochlorothiazide (analysis of variance, p = 0.5263)). Glomerular filtration rate did not vary. The aldosterone to active renin ratio was decreased by angiotensin I converting enzyme inhibition and increased by sodium depletion, showing treatment efficacy. CONCLUSION Angiotensin I converting enzyme inhibition by enalapril effectively reduces microalbuminuria in normotensive diabetic patients whereas hydrochlorothiazide is not effective. Changes in blood pressure and activity of the renin-angiotensin-aldosterone system may contribute to these different effects.