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.

Significantly Rapid Relief from Steroid-Resistant Nephrotic Syndrome by LDL Apheresis Compared with Steroid Monotherapy

“…Considering the rapid improvement of nephrotic proteinuria obtained by short intervals between LDL-A procedures [10], it seemed reasonable to perform LDL-A at least twice a week, especially at the beginning of treatment. This protocol was also supported by the recent analysis of cholesterol kinetics during LDL-A in nephrotic hypercholesterolemia in which the serum cholesterol levels were maintained at <250 mg/dl by the same protocol as in the present study [11]. In this study, we first compared the clinical data and the effect of the therapy between those treated both with steroid and LDL-A and those treated only with steroid to evaluate the effect of LDL-A.…”

Estimation of Filtration Coefficients and Circulating Plasma Volume by Continuously Monitoring Hematocrit during Hemodialysis

“…Model parameters for the filtration coefficient (Lp) and for the initial circulating plasma volume (Vp0) were estimated so as to fit calculated values of Ht to actual values measured using the CRIT-LINE monitor by the nonlinear least square method [6]. Fifteen points of Ht were used for fitting (Ht at 0, 1, 3, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55 and 60 min after the start of ultrafiltration).…”

“…Model parameters for the filtration coefficient (Lp) and for the initial circulating plasma volume (Vp0) were estimated so as to fit calculated values of Ht to actual values measured using the CRIT-LINE monitor by the non-linear least square method [6]. Briefly, the numerical solutions to the simultaneous differential equations and Ht were calculated using tentative values of filtration coefficient (Lp) and initial circulating plasma volume (Vp0) by the Runge-Kutta-Gill method.…”

“…Despite ultrafiltration of relatively large volumes of fluid compared with the circulating blood volume during TP-pre g/dl 4 BW-pre kg 5 BW gain kg 6 Flow rate ml/min Hypo. 7 CTR % 8…”

“…5 Body weight before hemodialysis session. 6 Body weight gain from dry weight. 7 Hypotension during hemodialysis session (1: hypo(+), 2: hypo(-)).…”