Review Article | Published:

Statins in the management of dyslipidemia associated with chronic kidney disease

Nature Reviews Nephrology volume 8, pages 214223 (2012) | Download Citation

Abstract

The cause of death in the majority of patients with chronic kidney disease (CKD) and end-stage renal disease (ESRD) is accelerated cardiovascular disease and not renal failure per se, suggesting a role for statin therapy in this setting. During the past 6 years three large, randomized, placebo-controlled studies of three different statins have been conducted in the dialysis population—but two of these studies did not demonstrate any benefits of statin therapy, and the third study showed only marginally positive results. To understand why statins have failed to reduce cardiovascular events in patients with ESRD, the basic mechanisms underlying the pathogenesis of dyslipidemia in CKD must be critically examined. The observed negative results in the clinical trials of statin therapy might also reflect the biomarkers and targets that were chosen to be evaluated. The characteristics of dyslipidemia in patients with CKD not yet requiring dialysis treatment differ markedly from those of individuals with established ESRD and form the basis for therapeutic recommendations. The potential adverse effects associated with statin therapy are important to consider in the management of dyslipidemia in patients with CKD.

Key points

  • Most patients with chronic kidney disease (CKD) or end-stage renal disease on dialysis die from accelerated cardiovascular disease (CVD); CVD risk is further exacerbated in patients on hemodialysis

  • CKD is associated with oxidative stress, inflammation and profound dysregulation of lipid metabolism, which collectively contribute to the accelerated progression of CVD

  • Cholesterol-lowering therapy with statins consistently reduces the risk of cardiovascular events in the general population

  • Contrary to expectations, statins showed little or no benefit as primary CVD prevention in three large clinical trials (4D, AURORA and SHARP) conducted in patients on dialysis

  • In the minority of patients with CKD and hypercholesterolemia, development and progression of CVD can be ameliorated by the administration of statins

  • Several factors contribute to CVD in patients on hemodialysis: accumulation of atherogenic oxidized lipoproteins; HDL cholesterol deficiency and dysfunction; hypertension; and vascular calcification (however, LDL cholesterol concentration is largely normal)

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Affiliations

  1. Division of Nephrology and Hypertension, University of Miami Miller School of Medicine, 1201 North West 16th Street, Miami, FL 33125, USA

    • Murray Epstein
  2.  Division of Nephrology and Hypertension, Schools of Medicine and Biological Science, University of California, Irvine, 101 The City Drive, City Tower, Suite 400, Orange, CA 92868, USA

    • Nosratola D. Vaziri

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Both authors contributed equally to researching data for the article, discussion of content and writing the article, and to review and/or editing of the manuscript before submission.

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The authors declare no competing financial interests.

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Correspondence to Murray Epstein.

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DOI

https://doi.org/10.1038/nrneph.2012.33

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