NON-STEADY-STATE KINETICS OF LOW-DENSITY LIPOPROTEINS IN MAN - STUDIES AFTER PLASMA-EXCHANGE IN HEALTHY-SUBJECTS AND PATIENTS WITH FAMILIAL HYPERCHOLESTEROLEMIA

Five patients with heterozygous familial hypercholesterolaemia (FH), one patient with non-familial hypercholesterolaemia, and four healthy normals were treated with plasma exchange (PE). In order to achieve a non-steady-state situation with low plasma cholesterol levels, PE was performed twice in each subject at an interval of 1-3 days. At each time, 1500 ml of plasma were removed and replaced with colloids and albumin. Lipoprotein analyses were performed daily in all subjects for a period of 14 days following PE. Kinetic calculation of LDL cholesterol data using a two-compartment open model was performed, and rate constants, synthetic rate and apparent clearance of LDL were determined. A lower clearance and a tendency towards a higher synthesis of LDL were observed in the FH patients. In four of the subjects, LDL kinetics was also studied with the conventional I-125-LDL turnover technique. The synthetic rates of LDL were compared using data derived from PE and I-125-LDL kinetics. The two techniques showed a good correlation (r = +0.93) although synthetic rates in general were higher when calculated from the I-125-LDL procedure (3.98 vs. 2.64 mmol d(-1) for LDL cholesterol synthesis). The results indicate that non-steady-state kinetics of LDL, as measured using the PE technique, is a useful method for analysis of LDL metabolism.