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IN-DEPTH REVIEW |
Division of Nephrology1 and Division of Critical Care Medicine,2 University of Alberta; Institute of Health Economics,3 Edmonton, Alberta, Canada
Correspondence to: M. Tonelli, Division of Nephrology, University of Alberta, 7-129 Clinical Science Building, 8440 112 Street, Edmonton, Alberta, T6G 2G3 Canada. mtonelli{at}ualberta.ca
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.
KEY WORDS: HMG-CoA reductase inhibitor; statin; chronic kidney disease; hemodialysis.
Received 29 March 2006; accepted 15 June 2006.
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