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Statins, inflammation and kidney disease

Nature Reviews Nephrology volume 7, pages 385–397 (2011)Cite this article

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Abstract

Inflammation is highly prevalent in patients with chronic kidney disease (CKD) and is consistently associated with cardiovascular morbidity and mortality. Clinical event rates increase with declining renal function and activation of the acute-phase response. Statins are potent anti-inflammatory drugs that reduce the incidence of cardiovascular events. Owing to the increased prevalence of inflammation in patients with CKD and the potent effect of statins in individuals with elevated levels of C-reactive protein, these drugs should be especially effective in patients with CKD. Whereas data indicate that pravastatin may prevent loss of kidney function to a greater extent in individuals with evidence of increased inflammation than in those who show no inflammation, two large, randomized statin trials in patients on hemodialysis found no benefit of statin therapy, neither in the whole study group nor after stratifying for inflammation. Irrespective of inflammation, guidelines recommend treatment of dyslipidemia in early stages of CKD, which is supported by results from recent meta-analyses, and the Study of Heart and Renal Protection (SHARP), a large, randomized, placebo-controlled trial.

Key Points

  • Levels of C-reactive protein (CRP) increase with failing kidney function and are higher in patients on dialysis than in patients with coronary heart disease or healthy individuals

  • High CRP levels in patients on dialysis reflect underlying comorbidities and are the result of a chronic acute-phase response in various organ systems of the body

  • CRP levels are a predictor of all-cause mortality and cardiovascular events in patients with chronic kidney disease (CKD); however, data regarding CRP and loss of kidney function are not unequivocal

  • Statins have potent anti-inflammatory effects in patients with CKD, with individual statins having different effects on proteinuria and the loss of kidney function

  • At present, no data support an especially beneficial effect of statins in patients on hemodialysis who show evidence of inflammation

  • The primary outcome of SHARP (major atherosclerotic events) was reduced in patients with CKD stages 3–5 who were treated with simvastatin and ezetimibe, supporting guideline recommendations on management of hyperlipidemia in these patients

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Figure 1: Relationship between median CRP levels and estimated mean GFR.
Figure 2: Impaired kidney function leading to premature death.
Figure 3: Median high-sensitivity CRP levels in hemodialysis patients on placebo compared with statin treatment from baseline to 12 months.
Figure 4: Hazard ratios for the primary end point (cardiac death, nonfatal myocardial infarction or nonfatal stroke) in subgroups of patients according to baseline concentrations of high-sensitivity CRP (tertiles of CRP within the AURORA study).

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Acknowledgements

C. P. Vega, University of California, Irvine, CA, is the author of and is solely responsible for the content of the learning objectives, questions and answers of the Medscape, LLC-accredited continuing medical education activity associated with this article.

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  1. Department of Medicine 1, Division of Nephrology, University of Würzburg, Oberdürrbacher Straβe 6, Würzburg, 97080, Germany

    Vera Krane & Christoph Wanner

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Supplementary Table 1

Lists studies including more than 10 participants with CKD on statins. (DOC 238 kb)

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Krane, V., Wanner, C. Statins, inflammation and kidney disease. Nat Rev Nephrol 7, 385–397 (2011). https://doi.org/10.1038/nrneph.2011.62

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