Lipid changes and statins in chronic renal insufficiency.
It has been known for a long time that chronic kidney disease (CKD) is associated with dyslipidemia, but the full extent of abnormalities has been appreciated only recently, because routine laboratory tests fail to disclose the entire spectrum of lipid abnormalities. Lipids, particularly HDL cholesterol, are predictive of cardiovascular events, but a paradoxic inverse relation between cholesterol concentration and cardiovascular death has been noted in uremic patients. This currently is thought to be explained by the confounding effect of microinflammation and possibly calcification, but this is not definitely proved. Several retrospective analyses that included patients with mild or moderate CKD documented benefit from lowering of cholesterol by statins. In contrast, the Die Deutsche Diabetes Dialyse (4D) study and a small Scandinavian study failed to show a benefit from lowering of cholesterol by statins in ESRD. Pathomechanistically, it is possible that nonclassical pathomechanisms override statin-sensitive mechanisms as also suggested by the observation that statins fail to reduce carotid intima-media thickening. Although, experimentally, exposure to lipids (particularly oxidized lipids) aggravates progression, data on the effect of statins on progression in patients with CKD are not definite. The most likely explanation is that the impact of numerous confounders obscures their effect on progression. The increase in urinary protein excretion of patients who are treated with statins had been a cause of concern, but the underlying mechanism (i.e. interference with proximal tubular reabsorption of protein) meanwhile has been well documented.
Ritz
Eberhard
E
Ruperto-Carola University Heidelberg, Heidelberg, Germany. prof.e.ritz@t-online.de
Wanner
Christoph
C
D050197:Atherosclerosis / Q000209:etiology / Q000378:metabolism; D018450:Disease Progression; D050171:Dyslipidemias / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D050356:Lipid Metabolism / Q000187:drug effects / Q000502:physiology; D051436:Renal Insufficiency, Chronic / Q000150:complications / Q000378:metabolism*
D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors