Catabolism of low-density lipoprotein is altered in experimental chronic renal failure

Catabolism of low-density lipoprotein is altered in experimental chronic renal failure. In patients with chronic renal failure, cardiovascular disease accounts for a significant proportion of all deaths. Several factors contribute to the "accelerated" atherosclerosis in this population, including hyperlipidemia, the pathogenesis of which is multifactorial. We investigated low-density lipoprotein (LDL) metabolism in a remnant model of chronic renal failure in the guinea pig. After one and two-thirds nephrectomy, creatinine clearance decreased to one-sixth normal. Plasma cholesterol and triglyceride (TG) levels increased with induction of renal failure. Analysis of lipoprotein composition disclosed significant TG enrichment of both uremic very-low-density lipoprotein (VLDL) and uremic LDL compared with control lipoproteins. Plasma clearance of homologous LDL was evaluated in turnover studies in control and uremic guinea pigs. To discriminate between differences in catabolism related to the uremic lipoprotein particle and to the uremic host milieu, a crossover protocol was used comparing the fractional catabolic rate (FCR) after simultaneous injection into control and uremic animals of 125I-control LDL and 131I-uremic LDL. The FCR of native LDL was slower in uremic animals than in controls. In addition, FCR of uremic LDL was significantly less than that of control LDL in both groups. Degradation studies in cultured fibroblasts indicated substantially reduced degradation of uremic LDL compared with control LDL. These results suggest dual abnormalities of LDL catabolism in renal failure that are not only related to alterations in clearance mechanisms in the uremic environment, but also suggest important functional differences in the LDL particle itself isolated from uremic animals.