Dyslipidemia of chronic renal failure: the nature, mechanisms, and potential consequences.
Chronic renal failure (CRF) results in profound lipid disorders, which stem largely from dysregulation of high-density lipoprotein (HDL) and triglyceride-rich lipoprotein metabolism. Specifically, maturation of HDL is impaired and its composition is altered in CRF. In addition, clearance of triglyceride-rich lipoproteins and their atherogenic remnants is impaired, their composition is altered, and their plasma concentrations are elevated in CRF. Impaired maturation of HDL in CRF is primarily due to downregulation of lecithin-cholesterol acyltransferase (LCAT) and, to a lesser extent, increased plasma cholesteryl ester transfer protein (CETP). Triglyceride enrichment of HDL in CRF is primarily due to hepatic lipase deficiency and elevated CETP activity. The CRF-induced hypertriglyceridemia, abnormal composition, and impaired clearance of triglyceride-rich lipoproteins and their remnants are primarily due to downregulation of lipoprotein lipase, hepatic lipase, and the very-low-density lipoprotein receptor, as well as, upregulation of hepatic acyl-CoA cholesterol acyltransferase (ACAT). In addition, impaired HDL metabolism contributes to the disturbances of triglyceride-rich lipoprotein metabolism. These abnormalities are compounded by downregulation of apolipoproteins apoA-I, apoA-II, and apoC-II in CRF. Together, these abnormalities may contribute to the risk of arteriosclerotic cardiovascular disease and may adversely affect progression of renal disease and energy metabolism in CRF.
Vaziri
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Division of Nephrology and Hypertension, UCI Medical Center, Orange, CA 92868, USA. ndvaziri@uci.edu
D002318:Cardiovascular Diseases / Q000209:etiology; D018450:Disease Progression; D050171:Dyslipidemias / Q000209:etiology* / Q000378:metabolism; D006801:Humans; D007676:Kidney Failure, Chronic / Q000150:complications* / Q000378:metabolism; D008055:Lipids / Q000097:blood; D008074:Lipoproteins / Q000378:metabolism*; D008954:Models, Biological
D008055:Lipids; D008074:Lipoproteins