Statins for Treatment of Dyslipidemia in Chronic Kidney Disease

Dyslipidemia is a potent cardiovascular (CV) risk factor in the general population. Elevated low-density lipoprotein cholesterol (LDL-C) and/or low high-density lipoprotein (HDL-C) are well-established CV risk factors, but more precise determinants of risk include increased apoprotein B (ApoB), lipoprotein(a) [Lp(a)], intermediate and very low-density lipoprotein (IDL-C, VLDL-C; “remnant particles”), and small dense LDL particles. Lipoprotein metabolism is altered in association with declining glomerular filtration rate such that patients with non dialysis-dependent chronic kidney disease (CKD) have lower levels of HDL-C, higher triglyceride, ApoB, remnant IDL-C, remnant VLDL-C, and Lp(a), and a greater proportion of oxidized LDL-C. Similar abnormalities are prevalent in hemodialysis (HD) patients, who often manifest proatherogenic changes in LDL-C in the absence of increased levels. Patients treated with peritoneal dialysis (PD) have a similar but more severe dyslipidemia compared to HD patients due to stimulation of hepatic lipoprotein synthesis by glucose absorption from dialysate, increased insulin levels, and selective protein loss in the dialysate analogous to the nephrotic syndrome. In the dialysis-dependent CKD population, total cholesterol is directly associated with increased mortality after controlling for the presence of malnutrition–inflammation. Treatment with statins reduces CV mortality in the general population by approximately one third, irrespective of baseline LDL-C or prior CV events. Statins have similar, if not greater, efficacy in altering the lipid profile in patients with dialysis-dependent CKD (HD and PD) compared to those with normal renal function, and are well tolerated in CKD patients at moderate doses (≤ 20 mg/day atorvastatin or simvastatin). Statins reduce C-reactive protein as well as lipid moieties such as ApoB, remnants IDL and VLDL-C, and oxidized and small dense LDL-C fraction. Large observational studies demonstrate that statin treatment is independently associated with a 30% – 50% mortality reduction in patients with dialysis-dependent CKD (similar between HD- and PD-treated patients). One recent randomized controlled trial evaluated the ability of statin treatment to reduce mortality in type II diabetics treated with HD (“4D”); the primary end point of death from cardiac cause, myocardial infarction, and stroke was not significantly reduced. However, results of this trial may not apply to other end-stage renal disease populations. Two ongoing randomized controlled trials (SHARP and AURORA) are underway evaluating the effect of statins on CV events and death in patients with CKD (including patients treated with HD and PD). Recruitment to future trials should be given a high priority by nephrologists and, until more data are available, consideration should be given to following published guidelines for the treatment of dyslipidemia in CKD. Additional consideration could be given to treating all dialysis patients felt to be at risk of CV disease (irrespective of cholesterol level), given the safety and potential efficacy of statins. This is especially relevant in patients treated with PD, given their more atherogenic lipid profile and the lack of randomized controlled trials in this population.