Long-term stabilizing effect of angiotensin-converting enzyme inhibition on plasma creatinine and on proteinuria in normotensive type II diabetic patients

Mordchai Ravid*, Hilel Savin, Itzhak Jutrin, Tamir Bental, Bernard Katz, Michael Lishner

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

754 Scopus citations


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.

Original languageEnglish
Pages (from-to)577-581
Number of pages5
JournalAnnals of Internal Medicine
Issue number8
StatePublished - 15 Apr 1993
Externally publishedYes


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