Renin-angiotensin system inhibitors in hypertensive adults with non-diabetic CKD with or without proteinuria: a systematic review and meta-analysis of randomized trials

The efficacy and safety of renin-angiotensin system inhibitors (RAS-I) in hypertensive adults with non-diabetic chronic kidney disease (CKD) differ depending on the presence or the absence of proteinuria. To estimate the effects of RAS-I in this population, we performed a systematic review and meta-analysis of randomized controlled trials where treatment with angiotensin-converting-enzyme inhibitors or angiotensin II receptor blockers were compared with placebo or active controls in adults with non-diabetic CKD. The treatment effects were separately reviewed in patients with and without proteinuria. Based on a search of Medline and the Cochrane Library up to September 2017, we identified 42 eligible trials (28, proteinuria-positive group; 6, proteinuria-negative group; 2, mixed-proteinuria group; and 6, proteinuria data-unavailable group). RAS-I reduced renal failure events in comparison to placebo or active agents in the proteinuria-positive group (relative risk [RR] 0.63, 95% confidence interval [CI] 0.52-0.75), but showed no significant effects on renal failure risk in the proteinuria-negative group (RR 0.64, 95% CI 0.18-2.30) although it reduced microalbuminuria. For cardiovascular events, RAS-I was not associated with a significantly reduced risk in both the proteinuria-positive and proteinuria-negative group (RR 0.77 and 1.06, 95% CI 0.51-1.16 and 0.85-1.32, respectively). In the mixed-proteinuria group and proteinuria data-unavailable group, RAS-I showed no significant effects on renal and cardiovascular events. Among adverse events, hyperkalemia increased with RAS-I administration in the proteinuria-positive group (RR 2.01, 95% CI 1.07-3.77). Our analysis showed the renoprotective effects of RAS-I treatment in patients with non-diabetic CKD having proteinuria, supporting its use as the first-line antihypertensive therapy in this population.