Mechanism for elevated plasma lipoprotein(a) concentrations in patients on dialysis: turnover studies

Plasma concentrations of lipoprotein (a) [Lp(a)] are increased in patients on renal replacement therapy. Lipoprotein (a) is increasingly being recognized as an independent cardiovascular risk factor. In an effort to explore the mechanism for elevation of Lp(a) in patients on dialysis we have performed turnover studies of Lp(a) with radioactive iodine. Lp(a) was isolated from 1 patient on hemodialysis (HD) and 1 patient on continuous ambulatory peritoneal dialysis (CAPD); the protein was labeled with 125I and returned to each patient. Lipoprotein (a) was subsequently isolated from the patients over a 15-day period and the decay of the specific radioactivity of Lp(a) was used to determine the fractional catabolic rate (FCR), which was 0.27 (pool/day) for the HD patient and 0.28 (pool/day) for the CAPD patient. These rates are indistinguishable from those measured in 4 patients with hypercholesterolemia (0.29, SEM = 0.01) and in 4 other familial hypercholesterolemic patients (0.29, SEM = 0.02) studied previously using the same method by Knight et al. (7). We found no difference in the FCR of patients on dialysis when compared to patients with hyperlipidemia and normal renal function. Increased plasma concentration of Lp(a) in our patients on renal replacement therapy is not due to decreased catabolism, but is caused by increased synthesis.