Effects of Renin–Angiotensin System Blockers on Renal Outcomes and All-cause Mortality in Patients With Diabetic Nephropathy: An Updated Meta-analysis

Background In contrast to previous studies, recent data questioned the ability of renin–angiotensin–aldosterone system (RAAS) blockers to delay progression of diabetic nephropathy. This study evaluated the effect of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin-receptor blockers (ARBs) in patients with diabetic nephropathy. Methods A systematic literature search of MEDLINE/PubMed and EMBASE databases was performed to identify randomized trials published up to June 2007 comparing the effects of ACEIs or ARBs with placebo and/or a regimen not including a RAAS blocker on the incidence of end-stage renal disease (ESRD), doubling of serum creatinine (DSC), or death from any cause in patients with diabetic nephropathy. Treatment effects were summarized as relative risks (RRs) using the Mantel–Haenszel fixed-effects model. Results Of the 1,028 originally identified studies, 24 fulfilled the inclusion criteria (20 using ACEIs and 4 using ARBs). Use of ACEIs was associated with a trend toward reduction of ESRD incidence (RR 0.70; 95% confidence interval (CI) 0.46–1.05) and use of ARBs with significant reduction of ESRD risk (RR 0.78; 95% CI 0.67–0.91). Both drug classes were associated with reduction in the risk of DSC (RR 0.71; 95% CI 0.56–0.91 for ACEIs and RR 0.79; 95% CI 0.68–0.91 for ARBs) but none affected all-cause mortality (RR 0.96; 95% CI 0.85–1.09 for ACEIs and RR 0.99; 95% CI 0.85–1.16 for ARBs). Conclusion Treatment of patients with diabetic nephropathy with a RAAS blocker reduces the risks of ESRD and DSC, but does not affect all-cause mortality. These findings are added to the evidence of a renoprotective role of RAAS blockers in such patients.