1,25-dihydroxyvitamin D synthesis after renal transplantation: the role of fibroblast growth factor 23 and cyclosporine.
1,25-dihydroxyvitamin D(3) (1,25D) is tightly regulated by circulating factors, containing fibroblast growth factor 23 (FGF23). However, this control is disturbed in chronic kidney disease. Renal transplantation (RTX) alters 1,25D homeostasis. To examine the clinical relevance of 1,25D in RTX, we drew blood samples from 27 renal transplant recipients (20 cyclosporine-based, seven non-cyclosporine-based) and examined serum concentrations of 25-hydroxyvitamin D(3) (25D), 1,25D, and FGF23. Our protocol for cyclosporine was as follows, an initial dose of 8 mg/kg two d before RTX, and subsequently adjusted on the basis of the pharmacokinetic profile. No baseline differences were observed between cyclosporine-based and non-cyclosporine-based regimens before RTX. All variables except 1,25D levels changed similarly between the two groups. In the cyclosporine-based regimen, 1,25D levels increased steeply on day 2 and re-increased from days 7 to 21. Post-transplant FGF23 levels sharply decreased until day 14. Interestingly, the cyclosporine-treated group revealed an unexpected tendency between circulating 1,25D and FGF23 on day 21. Multiple regression analyses indicated the cyclosporine pharmacokinetic profile as a significant predictor for 1,25D levels. Post-transplant 1,25D production is induced by a steep fall in serum FGF23 and prompt graft function on day 2; 1,25D levels thereafter may be stimulated by circulating abundant cyclosporine.
Sato
Tetsuhiko
T
Department of Transplant and Endocrine Surgery, Nagoya Daini Red Cross Hospital, Nagoya, Japan. tetsugar@hotmail.com
Fukagawa
Masafumi
M
Uchida
Kazuharu
K
Katayama
Akio
A
Nagasaka
Takaharu
T
Matsuoka
Susumu
S
Goto
Norihiko
N
Tominaga
Yoshihiro
Y
Kobayashi
Takaaki
T
Nakao
Akimasa
A
D000328:Adult; D002112:Calcifediol / Q000097:blood*; D016022:Case-Control Studies; D016572:Cyclosporine / Q000008:administration & dosage* / Q000493:pharmacokinetics; D005260:Female; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000097:blood*; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D016030:Kidney Transplantation; D008297:Male; D015854:Up-Regulation / Q000187:drug effects; D014807:Vitamin D / Q000031:analogs & derivatives* / Q000096:biosynthesis / Q000097:blood
C000717427:FGF23 protein, human; D007166:Immunosuppressive Agents; D014807:Vitamin D; D005346:Fibroblast Growth Factors; C097949:1,25-dihydroxyvitamin D; D000089703:Fibroblast Growth Factor-23; D016572:Cyclosporine; D002112:Calcifediol