LATE OUTCOME OF A CONTROLLED TRIAL OF ENALAPRIL TREATMENT IN PROGRESSIVE CHRONIC-RENAL-FAILURE - HARD END-POINTS AND INFLUENCE OF PROTEINURIA

An earlier controlled trial showed that over an average of 26 months, enalapril slowed the progression of chronic renal failure. Following completion of the trial, the patients continued to receive antihypertensive treatment according to ordinary clinical criteria. All but four patients in the enalapril group remained on that drug, and two patients in the control group were switched to an angiotensin-converting enzyme (ACE) inhibitor. In the present study the fate of the 70 patients 44 months after termination of the trial was investigated, with a total follow-up of around 7 years. In the original enalapril group, 12 of the 35 patients (34%) were alive without renal replacement therapy versus five of the 35 patients (14%) in the control group. This difference of 20% in favour of having been in the enalapril group in the original trial was significant (P=0.05; 95% confidence limits 0.5-39.5%). The influence of baseline proteinuria on clinical outcome was analysed. In the original control group, baseline renal clearances of albumin (C-alb) and immunoglobulin G (C-IgG) were significantly lower in patients surviving without renal replacement therapy at follow-up than in patients who ultimately developed end-stage renal failure (ESRF) (P<0.05). In the original enalapril group, these baseline clearances were equal in the two renal outcome groups. In all patients, baseline C-alb and C-IgG were negatively correlated with the rate of change In GFR during the controlled trial (r=-0.37, P<0.01 and r=-0.28, P<0.05). In all patients alive without renal replacement therapy at follow-up, independent of their original treatment, the initial (1-8 weeks) fractional C-alb was 79% of baseline, significantly less than 100% inpatients who ultimately developed ESRF (P<0.05). Baseline total plasma cholesterol was lower in patients alive without replacement therapy, 5.8 (range, 4.5-8.8) as compared with 6.9 (4.4-12.7)mmol/l in patients with ultimate ESRF (P<0.05) and 7.2 (5.3-9.2)mmol/l in patients with non-renal death (P<0.05). The clinical outcome was not associated with differences in baseline high-density lipoprotein or plasma triglyceride. These observations suggest that enalapril treatment improves long-term dialysis-free survival in patients with progressive chronic renal failure. Renal function outcome appears to be influenced by the magnitude and type of proteinuria, the initial antiproteinuric response to treatment, and the plasma cholesterol level.