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

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.