Summary
Animal studies have shown that cyclosporin A (CyA) stimulates renal 25-hydroxyvitamin D3 [25(OH)D3]-1α-hydroxylase activity; in contrast, studies in renal transplant recipients indirectly suggest that CyA reduces 1α,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.
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Abbreviations
- CyA:
-
cyclosporin A
- Aza:
-
azathioprine
- 25(OH)D3 :
-
25-hydroxyvitamin D3
- 1,25(OH)2D3 :
-
1α,25-dihydroxyvitamin D3
- PTH:
-
parathyroid hormone
- C-PTH:
-
carboxyterminal-PTH
- AP:
-
alkaline phosphatase
- Ccr:
-
endogenous creatinine clearance
- gamma-GT:
-
gamma-glutamyltransferase
References
Aubia J, Masramon J, Serrano S, Lloveras J, Marinoso L (1988) Bone histology in renal transplant patients receiving cyclosporin. Lancet 1:1048
Bishop JE, Norman AW, Coburn JW, Roberts PA, Henry HL (1980) 25-Hydroxyvitamin D3, 24,25-dihydroxyvitamin D and 1,25-dihydroxyvitamin D in a single two-milliliter plasma sample. Miner Electrolyte Metab 3:235–343
Freitag J, Martin KJ, Hruska KA, Anderson C, Conrades M, Ladendon J, Klahr S, Slatopolsky E (1978) Impaired parathyroid hormone metabolism in patients with chronic renal failure. N Engl J Med 298:29–32
Graziani G, Adami S, De Vecchi A, Braga V, Zubani R, Casati S (1987) L'idrossilazione della vitamina D nel rene trapiantato. In: Nefrologia Proc 28th Congresso Soc Italiana di Nefrologia. Acta Medica Roma, pp 503–506
Hahn TJ, Boisseau VC, Avioli LV (1974) Effect of chronic corticosteroid administration on diaphyseal and metaphyseal bone mass. J Clin Endocrinol Metab 39:274–282
Hahn TJ, Baran DT, Halsted LR (1981) Effects of shortterm glucocorticoid administration on intestinal calcium absorption and circulating vitamin D metabolites. J Clin Endocrinol Metab 52:111–115
Kappos L, Patzold U, Dommasch D, Poser S, Haas J, Krausenek P, Malin JP, Fierz W, Graffenried BU, Gurgerli US (1988) Cyclosporine versus azathioprine in the long-term treatment of multiple sclerosis — results of the German multicenter study. Ann Neurol 23:56–63
Kopp JB, Klotman PE (1990) Cellular and molecular mechanisms of cyclosporin nephrotoxicity. J Am Soc Nephrol 1:162–179
Loertscher R, Thiel G, Harder F, Brunner FP (1983) Persistent elevation of alkaline phosphatase in cyclosporine-treated renal transplant recipients. Transplantation 36:115–116
Lucas PA, Brown RC, Woodhead JS (1988) Vitamin D3 metabolites in chronic renal failure and after renal transplantation. Nephrol Dial Transplant 3:70–76
Markovitz ME, Rotkin L, Rosen JF (1981) Circadian rhythms of blood minerals in humans. Science 213:672–674
Mawer EB, Hayes ME, Lee YA, Chalmers RJ, Edwards BD, Ballardie FW (1991) Cyclosporin A does not increase serum 1α,25(OH)2D3 in psoriasis patients. In: Norman AW, Bouillon R, Thomasset M (eds) Vitamin D, gene regulation, structure-function analysis and clinical application. Walter de Gruyter, Berlin, pp 428–429
Myers BD, Ross J, Newton L, Loertcher J, Perlroth M (1984) Cyclosporine-associated chronic nephropathy. N Engl J Med 311:699–705
Palestine AG, Ausin HA, Nussenblatt RB (1986) Renal tubular function in cyclosporine-treated patients. Am J Med 81:419–424
Poskitt EME, Cole TJ, Lawson DEM (1979) Diet, sunlight, and 25-hydroxyvitamin D in healthy children and adults. Br Med J 1:221–223
Rambausek M, Ritz E, Pomer S, Möhring K, Röhl L (1988) Alkaline phosphatase levels in renal transplant recipients receiving cyclosporine or azathioprine/steroids. Lancet 1:247
Reichel H, Deibert B, Schmidt-Gayk H, Ritz E (1991) Calcium metabolism in early chronic renal failure. Implications for pathogenesis of hyperparathyroidism. Nephrol Dial Transplant 6:162–169
Riancho JA, Francisco ALM de, Arco C del, Amado JA, Cotorruelo JG, Arias M, Gonzalez-Macias J (1988) Serum levels of 1,25-dihydroxyvitamin D after renal transplantation. Miner Electrolyte Metab 14:332–337
Scharla S, Schmidt-Gayk H, Reichel H, Mayer E (1984) A sensitive and simplified radioimmunoassay for 1,25-dihydroxyvitamin D3. Clin Chim Acta 142:325–338
Schlosberg M, Movsowitz C, Epstein S, Ismail F, Fallon MD, Thomas S (1989) The effect of cyclosporin A administration and its withdrawal on bone mineral metabolism in the rat. Endocrinology 124:2179–2184
Stein B, Halloran BP, Reinhardt T, Engstrom GW, Bales CW, Drezner MK, Currie KL, Takizawa M, Adams JS, Epstein S (1991) Cyclosporin-A increases synthesis of 1,25(OH)2D3 in the rat and mouse. Endocrinology 128:1369–1373
Zillikens D, Armbruster FP, Stern J, Schmidt-Gayk H. Raue F (1987) Sensitive homologous radioimmunoassay for human parathyroid hormone to diagnose hypoparathyroid conditions. Ann Clin Biochem 24:608–613
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Reichel, H., Grüßinger, A., Knehans, A. et al. Long-term therapy with cyclosporin A does not influence serum concentrations of vitamin D metabolites in patients with multiple sclerosis. Clin Investig 70, 595–599 (1992). https://doi.org/10.1007/BF00184801
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DOI: https://doi.org/10.1007/BF00184801