title: Effects of cyclosporine, tacrolimus and rapamycin on renal calcium transport and vitamin D metabolism.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Division of Nephrology, Department of Medicine, Chang-Gung Memorial Hospital, Kaohsiung Medical Center, Chang-Gung University College of Medicine, Gueishan, Taiwan, ROC.
authors.forename: Chien-Te
authors.initials: CT
authors.lastname: Lee
authors.forename: Hwee-Yeong
authors.initials: HY
authors.lastname: Ng
authors.forename: Yeong-Hau
authors.initials: YH
authors.lastname: Lien
authors.forename: Li-Wen
authors.initials: LW
authors.lastname: Lai
authors.forename: Mai-Szu
authors.initials: MS
authors.lastname: Wu
authors.forename: Chung-Ren
authors.initials: CR
authors.lastname: Lin
authors.forename: Hung-Chun
authors.initials: HC
authors.lastname: Chen
mesh_terms: D000818:Animals; D064092:Calbindin 1; D064026:Calbindins; D065095:Calcineurin Inhibitors; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000378:metabolism; D057167:Claudins / Q000378:metabolism; D016572:Cyclosporine / Q000494:pharmacology; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism*; D008274:Magnesium / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018167:Receptors, Calcitriol / Q000378:metabolism; D044169:Receptors, Calcium-Sensing / Q000378:metabolism; D064030:S100 Calcium Binding Protein G / Q000378:metabolism; D020123:Sirolimus / Q000494:pharmacology; D050916:TRPV Cation Channels / Q000378:metabolism; D016559:Tacrolimus / Q000494:pharmacology; D014807:Vitamin D / Q000378:metabolism*
chemical_list: C576499:Calb1 protein, mouse; D064092:Calbindin 1; D064026:Calbindins; D065095:Calcineurin Inhibitors; D015220:Calcium Channels; D057167:Claudins; D007166:Immunosuppressive Agents; D018167:Receptors, Calcitriol; D044169:Receptors, Calcium-Sensing; D064030:S100 Calcium Binding Protein G; D050916:TRPV Cation Channels; C492240:Trpv5 protein, mouse; C502010:claudin 16; D014807:Vitamin D; D016572:Cyclosporine; D008274:Magnesium; D002118:Calcium; D020123:Sirolimus; D016559:Tacrolimus