title: Two-compartment model of cholesterol kinetics for establishment of treatment strategy of LDL apheresis in nephrotic hypercholesterolemia.
abstract: Cholesterol kinetics in the time course after LDL apheresis using a dextran sulfate cellulose column was analyzed by adapting a two-compartment cholesterol kinetic model. Fifteen sets of serial serum cholesterol concentrations after LDL apheresis from 4 patients with drug-resistant nephrotic hypercholesterolemia due to focal glomerulosclerosis (FGS) were analyzed and cholesterol kinetic parameters were estimated with the nonlinear least-squares method. The fractional cholesterol catabolic rates (Kc; 0.171 +/- 0.073/day, mean +/- SD) were markedly decreased as reported in familial hypercholesterolemia (homo: 0.101/day, hetero: 0.280/day). Cholesterol generation rates (G; 68.0 +/- 28.7 mg/dl/day, mean +/- SD) considerably overlapped the normal range (39.2-77.5 mg/dl/day). This result was compatible with an earlier report that Kc was reduced earlier than G in nephrotic hypercholesterolemia. The time average serum cholesterol concentrations (TAC) in the rebound phase after LDL apheresis can be simulated using these kinetic parameters by the Runge-Kutta-Gill method. According to our previous report, TAC must be reduced to under a near-normal level in order to obtain a beneficial effect on nephrotic syndrome due to FGS. In 10 sets out of the 15, once-weekly treatment of LDL apheresis was sufficient to achieve this aim, but in the remaining 5 cases, more frequent LDL apheresis up to twice a week was necessary in the early phase of treatment. In conclusion, the two-compartment cholesterol kinetic model is useful in clarifying the abnormal cholesterol kinetics in nephrotic syndrome and may be helpful in establishing a more rational strategy of LDL apheresis for nephrotic hypercholesterolemia.
authors.affiliation: Artificial Kidney Division, Kyoto University Hospital, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Yashiro
authors.forename: E
authors.initials: E
authors.lastname: Muso
authors.forename: M
authors.initials: M
authors.lastname: Matsushima
authors.forename: R
authors.initials: R
authors.lastname: Nagura
authors.forename: K
authors.initials: K
authors.lastname: Sawanishi
authors.forename: S
authors.initials: S
authors.lastname: Sasayama
mesh_terms: D000293:Adolescent; D000328:Adult; D001781:Blood Component Removal / Q000379:methods*; D002784:Cholesterol / Q000097:blood*; D004351:Drug Resistance; D005260:Female; D006801:Humans; D006937:Hypercholesterolemia / Q000150:complications / Q000628:therapy*; D007700:Kinetics; D008297:Male; D008954:Models, Biological; D009404:Nephrotic Syndrome / Q000150:complications
chemical_list: D002784:Cholesterol