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

Reichel, Helmut; Grüssinger, A.; Knehans, Allen W.; Kühn, K; Schmidt‐Gayk, H.; Ritz, E.

doi:10.1007/bf00184801

Cited by 14 publications

(9 citation statements)

References 17 publications

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“…Grenet et al [19] previously demonstrated that CsA treatment raised both plasma and renal calcitriol levels. However, several other studies did not show consistent findings on the serum vitamin D level: the level might be unaltered or increased [10,20,21]. This variation may be due to differences in experimental designs, particularly treatment duration and the applied dosage.…”

Section: Discussionmentioning

confidence: 72%

Effects of Cyclosporine, Tacrolimus and Rapamycin on Renal Calcium Transport and Vitamin D Metabolism

Lee

Lien

et al. 2011

Am J Nephrol

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Background: Abnormalities in mineral metabolism are common complications of organ transplantation. The role of immunosuppressive agents in alteration of mineral metabolism is not clear. Methods: We conducted an animal study to investigate the effects of cyclosporine A (CsA), tacrolimus, and sirolimus on renal calcium, magnesium and vitamin D metabolism. Results: CsA and tacrolimus induced a 2- to 3-fold and 1.6- to 1.8-fold increase in urinary calcium and magnesium excretion, respectively, while rapamycin had no effects on calcium, but doubled the urinary magnesium excretion. CsA and tacrolimus, but not rapamycin, elevated serum 1,25(OH)₂ vitamin D without affecting the parathyroid hormone level. CsA and tacrolimus reduced mRNA abundance in TRPV5 (CsA: 64 ± 3% of control; tacrolimus: 50 ± 3%) calbindin-D28k (CsA: 62 ± 4%; tacrolimus: 43 ± 3%), and vitamin D receptor (CsA: 52 ± 3%; tacrolimus: 58 ± 2%, all p < 0.05). Rapamycin did not affect gene expression in any of studied proteins. The immunofluorescence staining study demonstrated a 50% reduction of TRPV5 and calbindin-D28k by CsA and tacrolimus. Conclusion: The suppression of VDR by calcineurin inhibitors is probably the underlying mechanism of renal calcium wasting. In spite of an increased 1,25(OH)₂ vitamin D level, the kidney is not able to reserve calcium, suggesting a role of vitamin D resistance that may be related to bone loss.

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Section: Discussionmentioning

confidence: 72%

Effects of Cyclosporine, Tacrolimus and Rapamycin on Renal Calcium Transport and Vitamin D Metabolism

Lee

Lien

et al. 2011

Am J Nephrol

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“…High-normal PTH concentrations were observed in patients with multiple sclerosis treated with CyA. 27 In contrast with animal studies, in humans, serum vitamin D metabolites, where measured, did not change. An additional mechanism leading to increased PTH levels may be mediated by serum magnesium concentrations.…”

Section: After Transplantationmentioning

confidence: 83%

Bone metabolism in orthotopic liver transplantation: A prospective study

et al. 1998

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Bone mineral density (BMD) and mineral metabolism were assessed in 54 patients with end-stage liver disease who were evaluated for orthotopic liver transplantation (OLT) and assessed 3, 6, and 12 months after surgery in 26 patients who underwent OLT. Serum and urinary electrolyte and mineral levels, serum liver function test results, and parathyroid hormone (PTH), osteocalcin (BGP), 25-hydroxyvitamin D, and urinary hydroxyproline levels were assessed. BMD of the lumbar spine was measured at baseline and 3, 6, and 12 months after OLT. At baseline, 40.7% of patients had BMD below the fracture threshold (0.800 g/cm 2 ). Using multiple stepwise regression analysis, we found that BMD was significantly (P F .0001) affected by age, serum creatinine level, and PTH level but not by indices of cholestasis or liver function. In the patients who underwent OLT, a 1.4% reduction (P F .006) was observed in BMD 3 months after OLT. Thereafter, BMD returned to pretransplant values. A significant increase in serum BGP was observed after 6 (P F .02) and 12 (P F .005) months. PTH levels increased progressively 3 (P F .02), 6 (P F .001), and 12 (P F .0001) months after OLT. This increase did not seem to be caused by cyclosporine-induced nephropathy. It was concluded that osteopenia is a major complication in hepatic cirrhosis, regardless of its causes. The increase in serum BGP levels 6 and 12 months after OLT indicates metabolic activation of osteoblasts. The increase in PTH levels after OLT warrants further investigation.

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“…We did not measure serum levels of 1,25(OH) 2 D 3 in this study. Clinical studies, however, have demonstrated that CsA at therapeutic dosages used in humans does not increase 1,25(OH) 2 D 3 serum levels in patients with multiple sclerosis or after renal transplantation (25,26) …”

Section: Discussionmentioning

confidence: 99%

Skeletal Effects of Low-Dose Cyclosporin A in Aged Male Rats: Lack of Relationship to Serum Testosterone Levels

Erben

Stangassinger

Gärtner

1998

Journal of Bone and Mineral Research

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The aim of this study was to investigate the skeletal effects of cyclosporin A (CsA) in a dose range relevant to clinical medicine in lumbar vertebral cancellous bone of aged male rats and to correlate these effects with possible changes in serum testosterone levels. Thirty-one 18-month-old male Wistar rats were divided into four weightmatched groups and subcutaneously injected with either 0, 1, 3, or 5 mg of CsA/kg of body weight three times per week. After 4 weeks of treatment, all rats were killed after in vivo fluorochrome labeling and the first lumbar vertebrae analyzed by quantitative histomorphometry. Serum was analyzed for total calcium, creatinine, alkaline phosphatase, osteocalcin, parathyroid hormone, total testosterone, and CsA levels. CsA administration resulted in a dose-dependent increase in serum osteocalcin levels and in histomorphometric indices of cancellous bone turnover in the axial skeleton. Furthermore, CsA-treated rats showed a deterioration of vertebral cancellous bone structure with increased discontinuity of the trabecular bone network due to trabecular plate perforations. Serum testosterone levels were not significantly changed by CsA treatment and were uncorrelated to all biochemical or histomorphometric indices of bone turnover. We conclude that the 4-week administration of CsA at doses that are close to those used in transplantation patients induced high turnover osteopenia in the axial skeleton of aged, 18-month-old male rats, and that these effects were likely not mediated by changes in serum testosterone levels. (J Bone Miner Res 1998;13:79-87)

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

Cited by 14 publications

References 17 publications

Effects of Cyclosporine, Tacrolimus and Rapamycin on Renal Calcium Transport and Vitamin D Metabolism

Effects of Cyclosporine, Tacrolimus and Rapamycin on Renal Calcium Transport and Vitamin D Metabolism

Bone metabolism in orthotopic liver transplantation: A prospective study

Skeletal Effects of Low-Dose Cyclosporin A in Aged Male Rats: Lack of Relationship to Serum Testosterone Levels

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