Meta Analysis in Lancet Finds No Unique Kidney Benefit for ACE Inhibitors or ARBs

An article published in the Lancet argues that there is no particular renoprotective effect of ACE inhibitors or angiotensin receptor blockers. As always, the results of meta analyses are questionable, but the results are provocative and go against current clinical guidelines. Via MedPage Today:

The best way to protect kidneys of diabetic patients is to lower blood pressure. Period.

So says Juan P. Casas M.D. and colleagues of the British Heart Foundation Laboratory at University College London, who reported that a meta-analysis of 127 randomized trials did not confirm a renoprotective effect for either ACE-inhibitors or angiotensin receptor blockers.

The purported benefit of either ACE inhibitors or ARBs comes from placebo-controlled studies, Dr. Casas and colleagues reported in the Dec. 10 issue of The Lancet. But when these agents were compared with other antihypertensive drugs that also substantially reduce blood pressure "there was no evidence of a significant salutary effect of ACE inhibitors or ARBs on renal outcomes in patients with diabetes."

From the Lancet:

Background A consensus has emerged that angiotensin-converting-enzyme (ACE) inhibitors and angiotensin-II receptor blockers (ARBs) have specific renoprotective effects. Guidelines specify that these are the drugs of choice for the treatment of hypertension in patients with renal disease. We sought to determine to what extent this consensus is supported by the available evidence.

Methods Electronic databases were searched up to January, 2005, for randomised trials assessing antihypertensive drugs and progression of renal disease. Effects on primary discrete endpoints (doubling of creatinine and end-stage renal disease) and secondary continuous markers of renal outcomes (creatinine, albuminuria, and glomerular filtration rate) were calculated with random-effect models. The effects of ACE inhibitors or ARBs in placebo-controlled trials were compared with the effects seen in trials that used an active comparator drug.

Findings Comparisons of ACE inhibitors or ARBs with other antihypertensive drugs yielded a relative risk of 0·71 (95% CI 0·49–1·04) for doubling of creatinine and a small benefit on end-stage renal disease (relative risk 0·87, 0·75–0·99). Analyses of the results by study size showed a smaller benefit in large studies. In patients with diabetic nephropathy, no benefit was seen in comparative trials of ACE inhibitors or ARBs on the doubling of creatinine (1·09, 0·55–2·15), end-stage renal disease (0·89, 0·74–1·07), glomerular filtration rate, or creatinine amounts. Placebo-controlled trials of ACE inhibitors or ARBs showed greater benefits than comparative trials on all renal outcomes, but were accompanied by substantial reductions in blood pressure in favour of ACE inhibitors or ARBs.

Interpretation The benefits of ACE inhibitors or ARBs on renal outcomes in placebo-controlled trials probably result from a blood-pressure-lowering effect. In patients with diabetes, additional renoprotective actions of these substances beyond lowering blood pressure remain unproven, and there is uncertainty about the greater renoprotection seen in non-diabetic renal disease.

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