Effects of Cyclosporine, Tacrolimus and Rapamycin on Renal Calcium Transport and Vitamin D Metabolism.
Am J Nephrol. 2011 Jun 20;34(1):87-94.
Lee CT, Ng HY, Lien YH, Lai LW, Wu MS, Lin CR, Chen HC.
Division of Nephrology, Department of Medicine, Chang-Gung Memorial Hospital, Kaohsiung Medical Center, Chang-Gung University College of Medicine, Gueishan, Taiwan, ROC.
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.
- 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.
Copyright © 2011 S. Karger AG, Basel.
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