Dyslipidaemia and cardiorenal disease: mechanisms, therapeutic opportunities and clinical trials.
Dyslipidaemia is an important risk factor for the development of chronic kidney disease (CKD) and cardiovascular disease (CVD). CKD generates an atherogenic lipid profile, characterised by high triglycerides, low high-density lipoprotein (HDL) cholesterol and accumulation of small dense low-density lipoprotein (LDL) particles, comparable to that in the metabolic syndrome. These changes are due specifically to the effects of CKD on key enzymes, transfer proteins and receptors involved in lipid metabolism. Dyslipidaemia is further compounded by dialysis, immunosuppressive drugs, and concomitant diseases such as diabetes mellitus. Post hoc analyses from large intervention trials suggest the benefit of statins in patients with early CKD, but prospective clinical trials in haemodialysis (HD) and renal transplant recipients have not conclusively shown improvements in hard cardiovascular end-points. The lack of efficacy of statins in late-stage CKD could be a consequence of other disease processes, such as calcific arteriopathy and insulin resistance, which are not modified by lipid-lowering agents. Despite uncertainty and pending the results of ongoing statin trials such as Study of Heart and Renal Protection (SHARP) and AURORA (A study to evaluate the Use of Rosuvastatin in subjects On Regular haemodialysis: an Assessment of survival and cardiovascular events), major international guidelines continue to support statin therapy in CKD and renal transplant patients to reduce cardiovascular risk burden. Because of increased risk of toxicity, particularly myopathy, statins and other lipid-regulating agents should be used cautiously in CKD and renal transplant recipients.
Chan
Doris T
DT
Metabolic Research Centre, School of Medicine and Pharmacology, University of Western Australia, Perth, Western Australia 6000, Australia.
Irish
Ashley B
AB
Dogra
Gursharan K
GK
Watts
Gerald F
GF
D002318:Cardiovascular Diseases / Q000209:etiology*; D002986:Clinical Trials as Topic; D050171:Dyslipidemias / Q000150:complications* / Q000628:therapy*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use; D007676:Kidney Failure, Chronic / Q000209:etiology*; D008055:Lipids / Q000097:blood; D008074:Lipoproteins / Q000097:blood; D009404:Nephrotic Syndrome / Q000150:complications; D017410:Practice Guidelines as Topic
D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008055:Lipids; D008074:Lipoproteins