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


METHODS
Randomized, double-blind, placebo-controlled trial. Each patient was followed for 5 years.


METHODS
Six clinics for diabetes mellitus coordinated by a department of medicine in a university hospital in Israel.


METHODS
Ninety-four normotensive, type II diabetic patients with microalbuminuria and normal renal function.


METHODS
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.


METHODS
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.
Ravid
M
M
Sackler Faculty of Medicine, Tel Aviv University, Israel.
Savin
H
H
Jutrin
I
I
Bental
T
T
Katz
B
B
Lishner
M
M
D000328:Adult; D000419:Albuminuria / Q000188:drug therapy* / Q000209:etiology; D001794:Blood Pressure / Q000187:drug effects; D003404:Creatinine / Q000097:blood*; D003924:Diabetes Mellitus, Type 2 / Q000150:complications* / Q000503:physiopathology; D003928:Diabetic Nephropathies / Q000188:drug therapy*; D004311:Double-Blind Method; D004656:Enalapril / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007677:Kidney Function Tests; D008297:Male; D008875:Middle Aged; D009543:Nifedipine / Q000627:therapeutic use; D011446:Prospective Studies; D013997:Time Factors
D004656:Enalapril; D003404:Creatinine; D009543:Nifedipine