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.