Clinical impact of cyclosporine cellular pharmacodynamics in minimal change nephrotic syndrome

Background: Cellular pharmacodynamics of cyclosporine (INN, cyclosporin) is considered to be closely implicated in clinical efficacy of the drug in ki dney transplantation and other immunologic disorders. We applied this strat egy to patients with minimal change nephrotic syndrome to predict individua l clinical efficacy of cyclosporine. Methods: Drug sensitivity tests were carried out with peripheral blood mono nuclear cells from 31 patients with minimal change nephrotic syndrome. The 50% lymphocyte-mitosis inhibition of cyclosporine on in vitro blastogenesis of peripheral blood mononuclear cells stimulated with concanavalin A were estimated, and interpatient variations of 50% lymphocyte-mitosis inhibition were evaluated. The relationship between cyclosporine-50% lymphocyte-mitos is inhibition and clinical outcomes indicated a decrease of urinary protein and the period required for complete remission under cyclosporine therapy was examined in 14 patients. me also evaluated the correlation between cycl osporine-50% lymphocyte-mitosis inhibition and interleukin-2 production and percentages of interleukin 2 receptor-positive peripheral blood mononuclea r cells in vitro. Results: Cyclosporine 50% lymphocyte-mitosis inhibition on peripheral blood mononuclear cell blastogenesis deviated largely between patients from 0.2 to 86.0 ng/mL, We found a statistically significant negative correlation be tween cyclosporine-50% lymphocyte-mitosis inhibition in vitro and decreasin g rates of urinary protein at 1 week after onset of cyclosporine administra tion (r = -0.655, P < .02), When we arbitrarily divide the 14 patients who received cyclosporine therapy according to their median 50% lymphocyte-mito sis inhibition of cyclosporine into two groups, that is, a high-sensitivity group (50% lymphocyte-mitosis inhibition < 18.1 ng/mL, n = 6) and a low-se nsitivity group (50% lymphocyte mitosis inhibition > 18.1 ng/mL, n = 8), th e period required for complete remission was significantly shorter in the h igh-sensitivity group (P < .03), The 50% lymphocyte-mitosis inhibition of c yclosporine on interleukin-2 production in culture medium was correlated wi th 50% lymphocyte-mitosis inhibition of the drug on peripheral blood mononu clear cell blastogenesis (r = 0.806, P < .02), Decreasing rates of interleu kin-2R-positive cells by cyclosporine treatment in vitro were negatively co rrelated with peripheral blood mononuclear cells blastogenesis in the prese nce of the drug (r = -0.694, P < .02), Conclusions: Peripheral blood mononuclear cell response to cyclosporine in vitro is closely related to clinical efficacy of the drug in minimal change nephrotic syndrome. Peripheral blood mononuclear cell resistance to cyclos porine was correlated with ability of the cells to express interleukin 2 an d interleukin 2R.