Lipid and lipoprotein metabolism in chronic kidney disease.

The risk of cardiovascular events and mortality increases as renal function declines although the relative risk of mortality contributed by the standard Framingham risk factors are altered or replaced. Low-density lipoprotein (LDL) cholesterol does not predict mortality but low high-density lipoprotein (HDL) cholesterol and triglycerides remain risk factors. The lipoproteins within each class are shifted to smaller, more dense isoforms. The accumulation of apolipoprotein B-containing lipoproteins, including lipoprotein(a) results primarily from decreased clearance rather than from increased synthesis. Lipoprotein(a) levels are also associated with cardiovascular outcome among dialysis patients. Decreased clearance of very low-density lipoprotein and intermediate-density lipoprotein is a result of decreased lipoprotein lipase, structural alterations in the lipoproteins rendering them poorer substrates, and a decrease in receptor number for these proteins. HDL levels are decreased as a result of an increased fractional catabolic rate both among obese patients with normal renal function and among dialysis patients, but the mechanisms responsible for increased HDL fractional catabolic rate may differ. In patients with advanced kidney disease, HDL fails to mature normally as a result of decreased lecithin cholesterol ester transfer protein, leaving cholesterol ester-poor, triglyceride-rich HDL(3) and pre-beta HDL. HDL in patients with chronic kidney disease is a less effective antioxidative agent than is HDL from normal subjects because of a decrease in paroxonase activity, allowing the accumulation of oxidized LDL.