Effect of renin-angiotensin-aldosterone system blockade in adults with diabetes mellitus and advanced chronic kidney disease not on dialysis: a systematic review and meta-analysis.

The presumed superiority of renin-angiotensin-aldosterone system (RAAS)-blocking agents over other antihypertensive agents in patients with diabetes to delay development of endstage kidney disease (ESKD) has recently been challenged. In addition, there is ongoing uncertainty whether RAAS-blocking agents reduce mortality and/or delay ESKD in patients with diabetes and chronic kidney disease (CKD) stages 3-5. In this subgroup, there might be an expedited need for renal replacement therapy (RRT) when RAAS-blocking agents are used. We conducted a meta-analysis of randomized controlled trials (RCTs) of at least 6-months duration in adult patients with diabetes who also have non-dialysis CKD stages 3-5. RCTs comparing single RAAS-blocking agents to placebo or alternative antihypertensive agents were included. Outcomes of interest were allcause mortality, cardiovascular morbidity, progression of renal function, ESKD and adverse events. A total of nine trials (n=9797 participants with CKD stages 3-5) fit our inclusion criteria. There was no difference between the RAAS group and control group regarding all-cause mortality {relative risk [RR]=0.97 [95% confidence interval (CI) 0.85-1.10]}, cardiovascular mortality [RR=1.03 (95% CI 0.75-1.41)] and adverse events [RR=1.05 (95% CI 0.89-1.25)]. There was a trend for a favourable effect for non-fatal cardiovascular events [RR=0.90 (95% CI 0.81-1.00)] and a lower risk of the composite endpoint need for RRT/doubling of serum creatinine [RR=0.81 (95% CI 0.70-0.92)] in the RAAS-blocking agents group versus the control group. We found evidence that in patients with diabetes mellitus and CKD stages 3-5, treatment with RAAS-blocking agents did not result in a clear survival advantage. The effect on renal outcomes did depend on the selected outcome measure. However, we did not find evidence that the use of RAASblocking agents expedited the need for RRT in patients with CKD stages 3-5. [ABSTRACT FROM AUTHOR]