FGF23 and mineral metabolism in the early post-renal transplantation period
- 436 Downloads
The relationship between fibroblast growth factor 23 (FGF23) and vitamin D production and catabolism post-renal transplantation has not been characterized.
Circulating creatinine, calcium, phosphorus, albumin, parathyroid hormone, FGF23, and 1,25(OH)2 vitamin D (calcitriol) values were obtained pre-transplantation, daily post-operatively for 5 days, and at 6 months post-transplantation in 44 patients aged 16.4 ± 0.4 years undergoing renal transplantation at UCLA from 1 August 2005 through to 30 April 2007. 25(OH) Vitamin D and 24,25(OH)2 vitamin D concentrations were obtained at baseline and on post-operative days 5 and 180, and urinary concentrations of creatinine, phosphorus, and FGF23 were measured on post-operative days 1, 3, 5, and 180.
Circulating phosphate concentrations declined more rapidly and the fractional excretion of phosphorus was higher in the first week post-transplantation in subjects with higher FGF23 values. Fractional excretion of FGF23 was low at all time-points. Circulating 1,25(OH)2 vitamin D levels rose more rapidly and were consistently higher in patients with lower FGF23 values; however, 25(OH) vitamin D and 24,25(OH)2 vitamin D values were unrelated to FGF23 concentrations.
Inhibition of renal 1α-hydroxylase, rather than stimulation of 24-hydroxylase, may primarily contribute to the relationship between FGF23 values and calcitriol. The rapid decline in FGF23 levels post-transplantation in our patient cohort was not mediated solely by the filtration of intact FGF23 by the new kidney.
KeywordsFGF23 PTH Vitamin D Renal transplantation Phosphorus
This work was supported in part by USPHS grants DK-67563, DK-35423, DK-51081, DK-073039, DK-080984, UL1 RR-033176 and UL1TR000124, PO1 DK11794, and by funds from the Casey Lee Ball Foundation. The authors would like to thank Barbara Gales and Georgina Ramos for their invaluable help in sample collection and storage for the current study.
H Jüppner is named on a patent describing the FGF-23 assay that was used in this study. None of the other authors of this paper have any financial interest in the information contained in this manuscript.
- 3.Fliser D, Kollerits B, Neyer U, Ankerst DP, Lhotta K, Lingenhel A, Ritz E, Kronenberg F, Kuen E, Konig P, Kraatz G, Mann JF, Muller GA, Kohler H, Riegler P (2007) Fibroblast growth factor 23 (FGF23) predicts progression of chronic kidney disease: the Mild to Moderate Kidney Disease (MMKD) Study. J Am Soc Nephrol 18:2600–2608PubMedCrossRefGoogle Scholar
- 4.Isakova T, Xie H, Yang W, Xie D, Anderson AH, Scialla J, Wahl P, Gutierrez OM, Steigerwalt S, He J, Schwartz S, Lo J, Ojo A, Sondheimer J, Hsu CY, Lash J, Leonard M, Kusek JW, Feldman HI, Wolf M (2011) Fibroblast growth factor 23 and risks of mortality and end-stage renal disease in patients with chronic kidney disease. JAMA 305:2432–2439PubMedCrossRefGoogle Scholar
- 5.Gutierrez OM, Januzzi JL, Isakova T, Laliberte K, Smith K, Collerone G, Sarwar A, Hoffmann U, Coglianese E, Christenson R, Wang TJ, deFilippi C, Wolf M (2009) Fibroblast growth factor 23 and left ventricular hypertrophy in chronic kidney disease. Circulation 119:2545–2552PubMedCrossRefGoogle Scholar
- 13.Larsson T, Nisbeth U, Ljunggren O, Jüppner H, Jonsson KB (2003) Circulating concentration of FGF-23 increases as renal function declines in patients with chronic kidney disease, but does not change in response to variation in phosphate intake in healthy volunteers. Kidney Int 64:2272–2279PubMedCrossRefGoogle Scholar
- 17.Isakova T, Xie H, Barchi-Chung A, Vargas G, Sowden N, Houston J, Wahl P, Lundquist A, Epstein M, Smith K, Contreras G, Ortega L, Lenz O, Briones P, Egbert P, Ikizler TA, Jueppner H, Wolf M (2011) Fibroblast growth factor 23 in patients undergoing peritoneal dialysis. Clin J Am Soc Nephrol 6:2688–2695PubMedCrossRefGoogle Scholar
- 20.Sanchez Fructuoso AI, Maestro ML, Calvo N, De La Orden V, Perez Flores I, Vidaurreta M, Valero R, Fernandez-Perez C, Barrientos A (2012) Role of fibroblast growth factor 23 (FGF23) in the metabolism of phosphorus and calcium immediately after kidney transplantation. Transplant Proc 44:2551–2554PubMedCrossRefGoogle Scholar
- 21.Kawarazaki H, Shibagaki Y, Fukumoto S, Kido R, Nakajima I, Fuchinoue S, Fujita T, Fukagawa M, Teraoka S (2011) The relative role of fibroblast growth factor 23 and parathyroid hormone in predicting future hypophosphatemia and hypercalcemia after living donor kidney transplantation: a 1-year prospective observational study. Nephrol Dial Transplant 26:2691–2695PubMedCrossRefGoogle Scholar
- 26.Shimada T, Urakawa I, Isakova T, Yamazaki Y, Epstein M, Wesseling-Perry K, Wolf M, Salusky IB, Jüppner H (2010) Circulating fibroblast growth factor 23 in patients with end-stage renal disease treated by peritoneal dialysis is intact and biologically active. J Clin Endocrinol Metab 95:578–585PubMedCrossRefGoogle Scholar
- 27.Bacchetta J, Dubourg L, Harambat J, Ranchin B, Bou-Jaoude P, Arnaud S, Carlier MC, Richard M, Cochat P (2010) The influence of glomerular filtration rate and age on fibroblast growth factor 23 serum levels in pediatric chronic kidney disease. J Clin Endocrinol Metab 95:1741–1748PubMedCrossRefGoogle Scholar