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  • Title: Long-term stabilizing effect of angiotensin-converting enzyme inhibition on plasma creatinine and on proteinuria in normotensive type II diabetic patients.
    Author: Ravid M, Savin H, Jutrin I, Bental T, Katz B, Lishner M.
    Journal: Ann Intern Med; 1993 Apr 15; 118(8):577-81. PubMed ID: 8452322.
    Abstract:
    OBJECTIVE: To evaluate the long-term effect of angiotensin-converting enzyme inhibition on proteinuria and on the rate of decline in kidney function in patients with type II diabetes mellitus and microalbuminuria. DESIGN: Randomized, double-blind, placebo-controlled trial. Each patient was followed for 5 years. SETTING: Six clinics for diabetes mellitus coordinated by a department of medicine in a university hospital in Israel. PATIENTS: Ninety-four normotensive, type II diabetic patients with microalbuminuria and normal renal function. INTERVENTION: The patients were randomly assigned to receive enalapril, 10 mg per day, or placebo. Any increase in blood pressure was treated with long-acting nifedipine. MEASUREMENTS: Albuminuria, blood pressure, serum creatinine, fasting blood glucose, and glycosylated hemoglobin levels, every 3 to 4 months. RESULTS: In the patients treated with enalapril, albuminuria decreased from 143 +/- 64 (mean +/- SD) mg/24 h to 122 +/- 67 mg/24 h during the first year. Thereafter, we observed a slow increase to 140 +/- 134 mg/24 h after 5 years. In the placebo group, albuminuria increased from 123 +/- 58 mg/24 h to 310 +/- 167 mg/24 h after 5 years. (Difference in rate of change in proteinuria [P < 0.05]). Kidney function (expressed as mean reciprocal creatinine) declined by 13% in the placebo group and remained stable (-1%) in the enalapril group (P < 0.05). Control of blood glucose levels remained stable, in both groups, throughout the study. The mean blood pressure was stable in the enalapril group (initial group mean, 99 +/- 2.1 mm Hg; fifth-year mean, 100 +/- 3.2 mm Hg) and increased in the placebo group from an initial mean value of 97 +/- 3.2 mm Hg to 102 +/- 3.4 mm Hg at the end of the study period (P = 0.082). CONCLUSIONS: In normotensive patients with diabetes mellitus type II, the institution of angiotensin-converting enzyme inhibition during early stages of diabetic nephropathy results in long-term stabilization of plasma creatinine levels and of the degree of urinary loss of albumin. These effects are probably independent of the antihypertensive action of these agents.
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