Blog entry by Meguid El Nahas

Anyone in the world
Prof David Goldsmith
Nephrol Dial Transplant (2017): 1–11

doi: 10.1093/ndt/gfx072

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

Ionut Nistor, Johan De Sutter, Christiane Drechsler, David Goldsmith,Maria Jose Soler, Charlie Tomson, Andrzej Wiecek, Mihaela-Dora Donciu, Davide Bolignano, Wim van Biesen and Adrian Covic

Correspondence and offprint requests to: Wim Van Biesen; E-mail:

The presumed superiority of renin–angiotensin–aldosterone
system (RAAS)-blocking agents over other antihypertensive
agents in patients with diabetes to delay development of end-stage 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 all-cause 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 [RR1.05 (95% CI 0.89–1.25)].

There was a trend for a favourable effect for non-fatal cardiovascular events [RR0.90 (95% CI 0.81–1.00)] and a lower risk of the composite endpoint need for RRT/doubling of serum creatinine [RR0.81 (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.


Another meta-analysis showing NO added advantage of RAAS Blockade over "other agents", in terms of cardioprotection.

As to renoprotection,

when will nephrologists learn that RAAS blockade impacts on tubular handling of creatinine and that creatinine/creatinine clearance related measured outcomes are confounded when these agents are used to assess CKD progression:

The nephrology world has been obssessed with these agents since the early 80s...time to put this myth to rest...

RAAS blockers do not offer advantages over and above good BP control, and RCTs that say otherwise are seriously flawed as shown in a thorough critical appraisal of these trials undertook a few years ago:



[ Modified: Thursday, 1 January 1970, 1:00 AM ]