Long-term effect of ACE inhibition on development of nephropathy in diabetes mellitus type II

Ninety-four normotensive, type II diabetics with microalbuminuria and normal renal function were randomized to receive enalapril or placebo and were followed for five years. In the patients treated with enalapril, albuminuria decreased initially from 143 ± 64 (mean ± SD) mg/24 hours to 122 ± 67 mg/24 hours, then a slow increase was observed to 140 ± 134 mg/24 hours after five years. In the placebo group albuminuria increased from 123 ±58 mg/24 hours to 3 10 ± 167 mg/24 hours after five years. The difference between the rates of change in albuminuria over time in the two groups was highly significant (P < 0.005). 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). The initial value of daily albuminuria was a good predictor of the subsequent decline in renal function (r = 0.86, P < 0.001 and r = 0.72, P < 0.001 for the enalapril and the placebo groups, respectively). Initial and subsequent mean values of cholesterol and LDL were lower in the enalapril than in the placebo group. There was a close correlation between mean cholesterol values and the decline in renal function (r = -0.58, P < 0.001). 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 97 ± 3.2 mm Hg to 102 ± 3.4 mm Hg at the end of the study (P = 0.082). In normotensive patients with diabetes mellitus type II, the institution of angiotensin-converting enzyme inhibition at the early stages of diabetic nephropathy results in long-term stabilization of serum creatinine levels and of the degree of urinary loss of albumin.