Influence of serum lipids on lymphocyte sensitivity to immunosuppressive drugs and its clinical implication in patients with nephrosis.

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I evaluated the cellular pharmacodynamics of cyclosporine in 24 patients with minimal change nephrotic syndrome. In vitro cyclosporine concentrations giving 50% inhibition of blastogenesis of PBMCs stimulated with concanavalin A (IC_<50>) were calculated. The cyclosporine IC_<50> values negatively correlated with the clinical cyclosporine efficacy assessed by a decreasing rate of urinary protein (r=-0.708, p=0.0006). Cyclosporine IC_<50>s significantly correlated with either serum total cholesterol (r=0.681, p=0.0003) or LDL-cholesterol (r=0.751, p=0.0034) concentrations. Furthermore, serum total-or LDL-cholesterol levels significantly correlated negatively with clinical cyclosporine efficacy (r=-0.613, p=0.0057 and r=-0.773, p=0.0399, respectively). Serum total-and LDL-cholesterol concentrations were significantly higher than those of 15 healthy subjects (p<0.005), while the percentages of LDL-receptor expressing cells in CD3-enriched PBMCs were not significantly different between these patients and healthy subjects. The data raised the possibility that hypercholesterolemia in patients with nephrotic syndrome attenuates cellular and clinical cyclosporine-pharmacodynamics. Individual deviation of PBMC-response to cyclosporine does not appear to be related to the difference of LDL-receptor positive cell numbers.