Effects of cyclosporine, tacrolimus and rapamycin on renal calcium transport and vitamin D metabolism

Chien Te Lee, Hwee Yeong Ng, Yeong Hau Lien, Li Wen Lai, Mai Szu Wu, Chung Ren Lin, Hung Chun Chen

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37 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)87-94
Number of pages8
JournalAmerican Journal of Nephrology
Volume34
Issue number1
DOIs
Publication statusPublished - Jul 2011
Externally publishedYes

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Keywords

  • Calcium transport
  • Immunosuppressants
  • Vitamin D

ASJC Scopus subject areas

  • Nephrology

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