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At which stage of chronic kidney disease should dyslipidemia be treated?

Nature Clinical Practice Nephrology volume 2, pages 176–177 (2006)Cite this article

Dyslipidemia of renal origin, which is characterized by raised serum triglyceride levels, low HDL-cholesterol levels and elevated LDL-cholesterol concentrations, is considered to be highly atherogenic. Individuals in the general population with this profile have been described as exhibiting an 'atherogenic lipoprotein phenotype'. Growing evidence indicates that all the components of this type of dyslipidemia are independently atherogenic, each conferring an atherogenic risk additional to that of LDL-cholesterol levels. Recognition of the increased cardiovascular risk and the atherogenic lipoprotein phenotype in patients with chronic kidney disease (CKD), together with a lack of direct evidence showing statins to be less effective in these patients than in the general population, prompted the development of the K/DOQI GUIDELINES on the management of hyperlipidemia in CKD patients. Unfortunately, these guidelines were formulated in the absence of data on cardiovascular and cerebrovascular outcomes in the CKD population, because patients with CKD were widely excluded from large prospective cardiovascular outcome trials. Importantly however, renal dysfunction can alter the pathogenesis of cardiovascular disease profoundly. In this Viewpoint, we will draw a distinction between each individual stage of CKD in attempting to answer the question of when hyperlipidemia should or should not be treated in this population, based on current data.

The effect of lipid-lowering therapy on cardiovascular, cerebrovascular, and renal outcomes in patients with CKD stages 2 to 3 was investigated in subgroup analyses of the Prospective Pravastatin Pooling Project.1 This trial, which recruited 12,333 subjects with mild (stage 2) CKD (Cockcroft–Gault glomerular filtration rate [GFR] 60–89.9 ml/min/1.73 m2) and 4,491 subjects with moderate (stage 3) CKD (Cockroft–Gault GFR 30–59.9 ml/min/1.73 m2), showed that 40 mg/day pravastatin produced a significant 6.3% reduction in the combined risk of nonfatal myocardial infarction (MI), coronary mortality, and percutaneous or surgical coronary revascularization in people with moderate CKD. Similar results were obtained in patients with mild CKD.1 Furthermore, in the ASCOT study, which enrolled 19,000 hypertensive patients with at least 3 other coronary artery disease risk factors and nonfasting cholesterol ≤6.5 mmol/l (≤250 mg/dl), prespecified subgroup analysis of 6,517 patients with kidney dysfunction revealed that atorvastatin 10 mg/day significantly reduced the risk of the primary endpoint, a composite of nonfatal MI and cardiac death, compared with placebo.2 Finally, of the 1,329 patients with serum creatinine levels of 110–200 µmol/l (1.24–2.26 mg/dl) who entered the Heart Protection Study, 182 of those who received simvastatin and 268 of those in the placebo group experienced a vascular event, indicating a proportional risk reduction with simvastatin of about one quarter.3

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Authors and Affiliations

  1. University Hospital of Würzburg and clinical coordinator of the 4D study,

    Vera Krane

  2. Division of Nephrology and Director of the Center of Clinical Research at the University Hospital of Würzburg, Germany

    Christoph Wanner

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  1. Vera Krane
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  2. Christoph Wanner
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Correspondence to Christoph Wanner.

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Competing interests

Dr Wanner has received lecture fees from Pfizer.

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Krane, V., Wanner, C. At which stage of chronic kidney disease should dyslipidemia be treated?. Nat Rev Nephrol 2, 176–177 (2006). https://doi.org/10.1038/ncpneph0129

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