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

Research output: Contribution to journalArticle

33 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 (US)
Pages (from-to)87-94
Number of pages8
JournalAmerican Journal of Nephrology
Volume34
Issue number1
DOIs
StatePublished - Jul 2011

Fingerprint

Tacrolimus
Sirolimus
Vitamin D
Cyclosporine
Calcium
Kidney
Calbindin 1
Magnesium
Ergocalciferols
Minerals
Calcitriol Receptors
Organ Transplantation
Immunosuppressive Agents
Parathyroid Hormone
Fluorescent Antibody Technique
Staining and Labeling
Gene Expression
Bone and Bones
Messenger RNA
Serum

Keywords

  • Calcium transport
  • Immunosuppressants
  • Vitamin D

ASJC Scopus subject areas

  • Nephrology

Cite this

Effects of cyclosporine, tacrolimus and rapamycin on renal calcium transport and vitamin D metabolism. / Lee, Chien Te; Ng, Hwee Yeong; Lien, Yeong Hau; Lai, Li-Wen; Wu, Mai Szu; Lin, Chung Ren; Chen, Hung Chun.

In: American Journal of Nephrology, Vol. 34, No. 1, 07.2011, p. 87-94.

Research output: Contribution to journalArticle

Lee, Chien Te ; Ng, Hwee Yeong ; Lien, Yeong Hau ; Lai, Li-Wen ; Wu, Mai Szu ; Lin, Chung Ren ; Chen, Hung Chun. / Effects of cyclosporine, tacrolimus and rapamycin on renal calcium transport and vitamin D metabolism. In: American Journal of Nephrology. 2011 ; Vol. 34, No. 1. pp. 87-94.
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