2-COMPARTMENT MODEL OF CHOLESTEROL KINETICS FOR ESTABLISHMENT OF TREATMENT STRATEGY OF LDL APHERESIS IN NEPHROTIC HYPERCHOLESTEROLEMIA

Cholesterol kinetics in the time course after LDL apheresis using a de xtran sulfate cellulose column was analyzed by adapting a two-compartm ent cholesterol kinetic model. Fifteen sets of serial serum cholestero l concentrations after LDL apheresis from 4 patients with drug-resista nt nephrotic hypercholesterolemia due to focal glomerulosclerosis (FGS ) were analyzed and cholesterol kinetic parameters were estimated with the nonlinear least-squares method. The fractional cholesterol catabo lic rates (Kc;0.171 +/- 0.073/day, mean +/- SD) were markedly decrease d as reported in familial hypercholesterolemia (home: 0.101/day, heter o: 0.280/day). Cholesterol generation rates (G; 68.0 +/- 28.7 mg/dl/da y, mean +/- SD) considerably overlapped the normal range (39.2-77.5 mg /dl/day). This result was compatible with an earlier report that Kc wa s reduced earlier than G in nephrotic hypercholesterolemia. The time a verage serum cholesterol concentrations (TAG) in the rebound phase aft er LDL apheresis can be simulated using these kinetic parameters by th e Runge-Kutta-Gill method. According to our previous report, TAC must be reduced to under a near-normal level in order to obtain a beneficia l effect on nephrotic syndrome due to FGS. In 10 sets out of the 15, o nce-weekly treatment of LDL apheresis was sufficient to achieve this a im, but in the remaining 5 cases. more frequent LDL apheresis up to tw ice a week was necessary in the early phase of treatment. In conclusio n, the two-compartment cholesterol kinetic model is useful in clarifyi ng the abnormal cholesterol kinetics in nephrotic syndrome and may be helpful in establishing a more rational strategy of LDL apheresis for nephrotic hypercholesterolemia.