EVIDENCE FOR INCREASED SYNTHESIS OF LIPOPROTEIN(A) IN THE NEPHROTIC SYNDROME

In patients with the nephrotic syndrome, markedly increased levels of lipoprotein(a) (Lp(a)) concentration have been frequently reported, an d it has been suggested that this may contribute to the increased card iovascular risk in these patients. The mechanism, however, is not clea r. In the present study, in vivo fractional synthesis rate of Lp(a) wa s measured using incorporation of the stable isotope C-13 valine. Unde r steady-state conditions, fractional synthesis rate equals fractional catabolic rate (FCR). FCR of Lp(a) was estimated in five patients wit h the nephrotic syndrome and compared with five control subjects. The mean plasma Lp(a) concentration in the patients (1749 +/- 622 mg/L) wa s higher than in control subjects (553 +/- 96 mg/L). Two patients were heterozygous for apolipoprotein(a) (range, 19 to 30 kringle IV domain s), whereas all control subjects were each homozygous with regard to a polipoprotein(a) phenotype (range, 18 to 28 kringle IV domains). The F CR of Lp(a) was comparable between control subjects (0.072 +/- 0.032 p ools/d) and patients (0.064 +/- 0.029 pools/d) despite the wide varian ce in plasma concentration. This suggests that differences in Lp(a) le vels are caused by differences in synthesis rate. Indeed, the absolute synthetic rate of Lp(a) correlated directly with plasma Lp(a) concent ration (P < 0.0001) in all subjects. The present results demonstrate t hat increased synthesis, rather than decreased catabolism, causes elev ated plasma Lp(a) concentrations in the nephrotic syndrome.