In order to achieve a higher degree of improvement in patients with postoperative hepatic failure, the effects of plasma adsorption (PA) using a serial connection of noncoated charcoal (N 350) and a new bilirubin adsorbent material, styrenedivinylbenzene (BR350), were investigated both experimentally and clinically. After in vitro perfusion of high bilirubin containing plasma through these columns for 3 hours, total bilirubin levels were drastically reduced to 21% of the preperfusion level in the serial connection of N 350 and BR 350, while it remained high at over 40% in the single use of each column. Total branched chain and aromatic amino acid levels were also drastically reduced in the serial connection of these columns to 50, 40, and 7%, respectively, while the total amino acid levels remained high at 87% in the single use of BR 350. The combination of these columns enhanced rather than interfered with one another. Patients who received this treatment achieved an initial reduction of plasma total bilirubin and aromatic amino acids of 57 _t 6 and 84 f 7, respectively. Although the Iongterm prognosis for these patients was negative, improvement of clinical and laboratory findings were actually obtained by this treatment. This PA system could provide a possibility for an improved supportive therapy for hepatic failure, especially for patients with hepatic coma and hyperbilirubinemia.

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.

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