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 c ompletion of the trial, the patients continued to receive antihyperten sive treatment according to ordinary clinical criteria. All but four p atients in the enalapril group remained on that drug, and two patients in the control group were switched to an angiotensin-converting enzym e (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 th e 35 patients (34%) were alive without renal replacement therapy versu s 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-a lb) and immunoglobulin G (C-IgG) were significantly lower in patients surviving without renal replacement therapy at follow-up than in patie nts 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 pat ients alive without renal replacement therapy at follow-up, independen t of their original treatment, the initial (1-8 weeks) fractional C-al b was 79% of baseline, significantly less than 100% inpatients who ult imately 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 E SRF (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 observ ations suggest that enalapril treatment improves long-term dialysis-fr ee 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 t he plasma cholesterol level.