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.

[1]  David W. Johnson,et al.  HMG CoA reductase inhibitors (statins) for dialysis patients. , 2009, The Cochrane database of systematic reviews.

[2]  J. Coresh,et al.  Prevalence of chronic kidney disease in the United States. , 2007, JAMA.

[3]  R. Foley,et al.  End-stage renal disease in the United States: an update from the United States Renal Data System. , 2007, Journal of the American Society of Nephrology : JASN.

[4]  P. O'Malley,et al.  Meta-Analysis: The Effect of Statins on Albuminuria , 2006, Annals of Internal Medicine.

[5]  M. Tonelli,et al.  Statins for improving renal outcomes: a meta-analysis. , 2006, Journal of the American Society of Nephrology : JASN.

[6]  João Costa,et al.  Efficacy of lipid lowering drug treatment for diabetic and non-diabetic patients: metaanalysis of randomised controlled trials , 2006, BMJ : British Medical Journal.

[7]  E. Rimm,et al.  The association of serum lipids and inflammatory biomarkers with renal function in men with type II diabetes mellitus. , 2006, Kidney international.

[8]  Jennifer G. Robinson,et al.  Pleiotropic effects of statins: benefit beyond cholesterol reduction? A meta-regression analysis. , 2005, Journal of the American College of Cardiology.

[9]  W. März,et al.  Atorvastatin in patients with type 2 diabetes mellitus undergoing hemodialysis. , 2005, The New England journal of medicine.

[10]  V. Campese,et al.  Are 3-hydroxy-3-methylglutaryl-CoA reductase inhibitors renoprotective? , 2005, Journal of the American Society of Nephrology : JASN.

[11]  N. Powe,et al.  Association between cholesterol level and mortality in dialysis patients: role of inflammation and malnutrition. , 2004, JAMA.

[12]  J. Slattery,et al.  Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S). 1994. , 1994, Atherosclerosis. Supplements.

[13]  D. Altman,et al.  Measuring inconsistency in meta-analyses , 2003, BMJ : British Medical Journal.

[14]  N J Wald,et al.  Quantifying effect of statins on low density lipoprotein cholesterol, ischaemic heart disease, and stroke: systematic review and meta-analysis , 2003, BMJ : British Medical Journal.

[15]  C. Baigent,et al.  Study of Heart and Renal Protection (SHARP). , 2003, Kidney international. Supplement.

[16]  A. Jardine,et al.  Why do we need a statin trial in hemodialysis patients? , 2003, Kidney international. Supplement.

[17]  K. Kalantar-Zadeh,et al.  Reverse epidemiology of cardiovascular risk factors in maintenance dialysis patients. , 2003, Kidney international.

[18]  A. Selwyn,et al.  Effects of statins on inflammation in patients with acute and chronic coronary syndromes. , 2003, The American journal of cardiology.

[19]  Ethan M Balk,et al.  K/DOQI clinical practice guidelines for chronic kidney disease: evaluation, classification, and stratification. , 2002, American journal of kidney diseases : the official journal of the National Kidney Foundation.

[20]  D. Sica,et al.  3-Hydroxy-3-methylglutaryl coenzyme A reductase inhibitors and rhabdomyolysis: considerations in the renal failure patient , 2002, Current opinion in nephrology and hypertension.

[21]  C. Zoccali,et al.  Hyperhomocysteinemia predicts cardiovascular outcomes in hemodialysis patients. , 2002, Kidney international.

[22]  European best practice guidelines for renal transplantation. Section IV: Long-term management of the transplant recipient. IV.5.3. Cardiovascular risks. Hyperlipidaemia. , 2002, Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association.

[23]  B. Kestenbaum,et al.  HMG-CoA reductase inhibitors are associated with reduced mortality in ESRD patients. , 2002, Kidney international.

[24]  F. Berthoux SECTION IV: Long-term management of the transplant recipient , 2002 .

[25]  Kdoqi Disclaimer K/DOQI clinical practice guidelines for chronic kidney disease: evaluation, classification, and stratification. , 2002, American journal of kidney diseases : the official journal of the National Kidney Foundation.

[26]  S. Ganesh,et al.  Association of elevated serum PO(4), Ca x PO(4) product, and parathyroid hormone with cardiac mortality risk in chronic hemodialysis patients. , 2001, Journal of the American Society of Nephrology : JASN.

[27]  Judy W. M. Cheng,et al.  Beneficial Effects of Statins in Coronary Artery Disease — Beyond Lowering Cholesterol , 2000, The Annals of pharmacotherapy.

[28]  W. Keane,et al.  The role of lipids in renal disease: future challenges. , 2000, Kidney international. Supplement.

[29]  Ebpg European Best Practice Guidelines for Renal Transplantation (part 1). , 2000, Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association.

[30]  Z. Massy,et al.  Incidence and risk factors of atherosclerotic cardiovascular accidents in predialysis chronic renal failure patients: a prospective study. , 1997, Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association.

[31]  S. Olson,et al.  Renal Dysfunction Does Not Alter the Pharmacokinetics or LDL‐Cholesterol Reduction of Atorvastatin , 1997, Journal of clinical pharmacology.

[32]  C. Hennekens,et al.  Cholesterol lowering with statin drugs, risk of stroke, and total mortality. An overview of randomized trials. , 1997, JAMA.

[33]  S. Kong,et al.  Efficacy of 3-hydroxy-3-methylglutaryl coenzyme a reductase inhibitors in the treatment of patients with hypercholesterolemia: a meta-analysis of clinical trials. , 1997, Clinical therapeutics.

[34]  T. Louis,et al.  Lipid-lowering therapy in patients with renal disease. , 1995, Kidney international.

[35]  Scandinavian Simvastatin Survival Study Group Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S) , 1994, The Lancet.

[36]  J. Stengård,et al.  Antibodies to glutamic acid decarboxylase as predictors of insulin-dependent diabetes mellitus before clinical onset of disease , 1994, The Lancet.

[37]  D. Wheeler,et al.  Lipid abnormalities in the nephrotic syndrome: causes, consequences, and treatment. , 1994, American journal of kidney diseases : the official journal of the National Kidney Foundation.

[38]  N J Wald,et al.  By how much and how quickly does reduction in serum cholesterol concentration lower risk of ischaemic heart disease? , 1994, BMJ.

[39]  H. Pan,et al.  Single‐Dose Pharmacokinetics of Pravastatin and Metabolites in Patients with Renal Impairment , 1992, Journal of clinical pharmacology.

[40]  B. Rifkind,et al.  The value of lowering cholesterol after myocardial infarction. , 1990, The New England journal of medicine.

[41]  N. Laird,et al.  Meta-analysis in clinical trials. , 1986, Controlled clinical trials.