Long-term therapy with cyclosporin A does not influence serum concentrations of vitamin D metabolites in patients with multiple sclerosis.
Animal studies have shown that cyclosporin A (CyA) stimulates renal 25-hydroxyvitamin D3 [25(OH)D3]-1 alpha-hydroxylase activity; in contrast, studies in renal transplant recipients indirectly suggest that CyA reduces 1 alpha,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 less than 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 less than 0.01). The urinary excretion of mineral ions, cations and protein was similar in both groups.(ABSTRACT TRUNCATED AT 250 WORDS)
Reichel
H
H
Medizinische Klinik, Universität Heidelberg.
Grüssinger
A
A
Knehans
A
A
Kühn
K
K
Schmidt-Gayk
H
H
Ritz
E
E
D000328:Adult; D001379:Azathioprine / Q000494:pharmacology / Q000627:therapeutic use; D002112:Calcifediol / Q000097:blood; D002117:Calcitriol / Q000097:blood*; D003401:Creatine / Q000097:blood; D016572:Cyclosporine / Q000494:pharmacology* / Q000627:therapeutic use; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007668:Kidney / Q000187:drug effects / Q000201:enzymology; D008297:Male; D009103:Multiple Sclerosis / Q000097:blood / Q000628:therapy* / Q000652:urine; D010281:Parathyroid Hormone / Q000097:blood; D014807:Vitamin D / Q000378:metabolism*
D010281:Parathyroid Hormone; D014807:Vitamin D; D016572:Cyclosporine; D002117:Calcitriol; D001379:Azathioprine; D003401:Creatine; D002112:Calcifediol