BMJ  2008;336:645-651 (22 March), doi:10.1136/bmj.39472.580984.AE (published 25 February 2008)

Research

Effects of statins in patients with chronic kidney disease: meta-analysis and meta-regression of randomised controlled trials

Giovanni F M Strippoli, editor of Cochrane Renal Group1,2,3, Sankar D Navaneethan, clinical fellow in nephrology4, David W Johnson, professor of nephrology5, Vlado Perkovic, associate director (clinical research)6, Fabio Pellegrini, biostatistician2, Antonio Nicolucci, head2, Jonathan C Craig, editor in chief of Cochrane Renal Group and associate professor of epidemiology1,3

1 NHMRC Centre for Clinical Research Excellence in Renal Medicine, School of Public Health, University of Sydney, Australia, 2 Department of Clinical Pharmacology and Epidemiology, Mario Negri Sud Consortium, S Maria Imbaro (Ch), Italy, 3 Cochrane Renal Group, Sydney, 4 Division of Nephrology, University of Rochester, 601 Elmwood Avenue, Box 675, NY 14623, USA, 5 University of Queensland, Brisbane, Australia, 6 George Institute for International Health, Sydney

Correspondence to: S D Navaneethan  sankardass{at}hotmail.com

Objective To analyse the benefits and harms of statins in patients with chronic kidney disease (pre-dialysis, dialysis, and transplant populations).

Design Meta-analysis.

Data sources Cochrane Central Register of Controlled Trials, Medline, Embase, and Renal Health Library (July 2006).

Study selection Randomised and quasi-randomised controlled trials of statins compared with placebo or other statins in chronic kidney disease.

Data extraction and analysis Two reviewers independently assessed trials for inclusion, extracted data, and assessed trial quality. Differences were resolved by consensus. Treatment effects were summarised as relative risks or weighted mean differences with 95% confidence intervals by using a random effects model.

Results Fifty trials (30 144 patients) were included. Compared with placebo, statins significantly reduced total cholesterol (42 studies, 6390 patients; weighted mean difference –42.28 mg/dl (1.10 mmol/l), 95% confidence interval –47.25 to –37.32), low density lipoprotein cholesterol (39 studies, 6216 patients; –43.12 mg/dl (1.12 mmol/l), –47.85 to –38.40), and proteinuria (g/24 hours) (6 trials, 311 patients; –0.73 g/24 hour, –0.95 to –0.52) but did not improve glomerular filtration rate (11 studies, 548 patients; 1.48 ml/min (0.02 ml/s), –2.32 to 5.28). Fatal cardiovascular events (43 studies, 23 266 patients; relative risk 0.81, 0.73 to 0.90) and non-fatal cardiovascular events (8 studies, 22 863 patients; 0.78, 0.73 to 0.84) were reduced with statins, but statins had no significant effect on all cause mortality (44 studies, 23 665 patients; 0.92, 0.82 to 1.03). Meta-regression analysis showed that treatment effects did not vary significantly with stage of chronic kidney disease. The side effect profile of statins was similar to that of placebo. Most of the available studies were small and of suboptimal quality; mortality data were provided by a few large trials only.

Conclusion Statins significantly reduce lipid concentrations and cardiovascular end points in patients with chronic kidney disease, irrespective of stage of disease, but no benefit on all cause mortality or the role of statins in primary prevention has been established. Reno-protective effects of statins are uncertain because of relatively sparse data and possible outcomes reporting bias.


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