Long-term therapy with cyclosporin A does not influence serum concentrations of vitamin D metabolites in patients with multiple sclerosis

Summary Animal studies have shown that cyclosporin A (CyA) stimulates renal 25-hydroxyvitamin D₃ 25(OH)D₃]-1-hydroxylase activity; in contrast, studies in renal transplant recipients indirectly suggest that CyA reduces 1,25-dihydroxyvitamin D₃ 1,25 (OH)₂D₃] production. To clarify the effect of CyA on vitamin D metabolite concentrations, we measured parameters of calcium metabolism in 37 CyA-treated patients (median trough whole blood levels 171–222 ng/ml) with multiple sclerosis and initially normal kidney function. The patients participated in a randomized double-blind study to assess the efficacy of CyA in multiple sclerosis. An age- and sex-matched control group (n = 39) received azathioprine (Aza). Measurements were made at the end of a 2-year treatment period. The 1,25(OH)₂D₃ serum concentrations were not significantly different between the two groups, although they were numerically lower in CyA-treated patients median (range), 28.4 pg/ml (7.8–85.9) vs 41.0 pg/ml (9.2–105.1) in Aza-treated patients]. The 25(OH)D₃ levels were comparable in both groups. There was no correlation between the 25(OH)D₃ and 1,25(OH)₂D₃ concentrations. The renal function in both groups was stable in the last 6 months of the study. At the end of the study period, the endogenous creatinine clearance was significantly lower in the CyA-treated group (85 ± 17 ml/min versus 99 ± 22 in the Aza-treated group, P < 0.05). The carboxyterminal parathyroid hormone (C-PTH) was within the normal range in both groups, although CyA-treated patients had significantly higher concentrations (P<0.01). The urinary excretion of mineral ions, cations and protein was similar in both groups. Our data suggest that long-term treatment with CyA does not cause clinically important alterations of vitamin D metabolism in humans. Subtle differences in the concentrations of 1,25(OH)₂D₃ and C-PTH between CyA- and Aza-treated patients result presumably from a slight impairment of renal function through CyA.Abbreviations CyA cyclosporin A - Aza azathioprine - 25(OH)D₃ 25-hydroxyvitamin D₃ - 1,25(OH)₂D₃ 1,25-dihydroxyvitamin D₃ - PTH parathyroid hormone - C-PTH carboxyterminal-PTH - AP alkaline phosphatase - Ccr endogenous creatinine clearance - gamma-GT gamma-glutamyltransferase