Lipoprotein metabolism and renal failure.

Lipoprotein metabolism is altered in the majority of patients with renal insufficiency and renal-failure, but may not necessarily lead to hyperlipidemia. The dyslipoproteinemia of renal disease has characteristic abnormalities of the apolipoprotein (apo) profile and lipoprotein composition. It develops during the asymptomatic stages of renal insufficiency and becomes more pronounced as renal failure advances. The qualitative characteristics of renal dyslipoproteinemia are not modified substantially by dialysis treatment. Patients with chronic renal disease may therefore be exposed to dyslipoproteinemia for long periods of time. The characteristic plasma lipid abnormality is a moderate hypertriglyceridemia. The alterations of lipoprotein metabolism affect both the apoB-containing very low-density and intermediate-density, and low-density lipoproteins and the apoA-containing high-density lipoproteins. The main underlying abnormality of lipoprotein transport is a decreased catabolism of the apoB-containing lipoproteins caused by decreased activity of lipolytic enzymes and altered lipoprotein composition. There is an increase of intact or partially metabolized, triglyceride-rich, apoB-containing lipoproteins with a disproportionate elevation of apoC-III and, to a lesser extent, apoE, resulting in a marked increase of the intermediate-density lipoproteins and an enrichment of triglycerides, apoC-III, and apoE in the low-density lipoproteins. In high-density lipoproteins there are decreases in the concentrations of cholesterol, apolipoproteins A-I and A-II, and the high-density lipoprotein-2 to high-density lipoprotein-3 ratio. These abnormalities result in a characteristic decrease of the apoA-I to apoC-III ratio and anti-atherogenic index apoA-I/apoB. The pathophysiologic links between the renal insufficiency and the abnormalities of lipoprotein transport are still poorly defined. Changes in the action of insulin on lipolytic enzymes, possibly mediated via increased levels of parathyroid hormone, have been suggested to play a contributory role. The clinical consequences of a defective lipoprotein transport may be related to the atherogenic character of lipoprotein abnormalities. Renal dyslipoproteinemia may contribute to the development of atherosclerotic vascular disease and progression of glomerular and tubular lesions with subsequent deterioration of renal function. Dietary and/or pharmacologic intervention may ameliorate the uremic dyslipoproteinemia, but the long-term clinical effects of such treatment have yet to be established.