CLINICAL STUDY Early post-transplantation hypophosphatemia is associated with elevated FGF-23 levels Andrea Trombetti 1 , Laura Richert 1 , Karine Hadaya 2,3 , Jean-Daniel Graf 4 , Franc ¸ois R Herrmann 1 , Serge L Ferrari 1 , Pierre-Yves Martin 2,3 and Rene ´ Rizzoli 1 1 Division of Bone Diseases, 2 Division of Nephrology, Department of Internal Medicine, 3 Service of Transplantation, Department of Visceral Surgery and 4 Central Laboratoryof Clinical Chemistry, University Hospitals and Faculty of Medicine of Geneva, Rue Gabrielle-Perret-Gentil 4, 1211 Geneva 14, Switzerland (Correspondence should be addressed to A Trombetti; Email: andrea.trombetti@unige.ch) Abstract Background: We examined the hypothesis that high FGF-23 levels early after transplantation contribute to the onset of hypophosphatemia, independently of parathyroid hormone (PTH) and other factors regulating phosphate metabolism. Methods: We measured serum phosphate levels (sPi), renal tubular reabsorption of Pi (TmPi/GFR), estimated GFR (eGFR), intact PTH (iPTH), calcitriol, intact (int) and C-terminal (Cter) FGF-23, dietary Pi intake and cumulative doses of glucocorticoids in 69 patients 12 days (95% confidence interval, 10–13) after renal transplantation. Results: Hypophosphatemia was observed in 43 (62%) of the patients 12 days after transplantation. Compared with non-hypophosphatemic subjects, their post-transplantation levels of intact and CterFGF-23 were higher (195 (108–288) vs 48 (40–64) ng/l, P!0.002 for intFGF-23; 205 (116–384) vs 81 (55–124) U/ml, P!0.002, for CterFGF-23). In all subjects, Cter and intFGF-23 correlated inversely with sPi (rZK0.35, P!0.003; K0.35, P!0.003, respectively), and TmPi/GFR (rZK0.50, P!0.001; K0.54, P!0.001, respectively). In multivariate models, sPi and TmPi/GFR were independently associated with FGF-23, iPTH and eGFR. Pre-transplant iPTH levels were significantly higher in patients developing hypophosphatemia after renal transplantation. Pre- transplant levels of FGF-23 were not associated with sPi at the time of transplantation. Conclusion: In addition to PTH, elevated FGF-23 may contribute to hypophosphatemia during the early post-renal transplant period. European Journal of Endocrinology 164 839–847 Introduction Hypophosphatemia related to decreased renal tubular reabsorption is a common complication following kidney transplantation, and is usually limited to the early post-transplant period (1, 2). However, in some cases, hypophosphatemia persists for more than 10 years after transplantation (3). Persistently elevated parathyroid hormone (PTH) levels have long been considered to be the cause of post-transplant hypophosphatemia, but hyperparathyr- oidism does not appear to be the only mechanism. Decreased renal tubular reabsorption may occur, despite low levels of PTH, and hypophosphatemia can persist even after elevated PTH levels have normalized (4–7). Furthermore, even if hypophosphatemia and hyperparathyroidism stimulate calcitriol (1,25-(OH) 2 -D 3 ) synthesis, calcitriol levels are often inappropriately low following renal transplantation, despite normal or mildly impaired allograft function. FGF-23 decreases renal tubular reabsorption of Pi and inhibits renal 1a-hydroxylase, which leads to decreased calcitriol synthesis. Recent studies suggest that high levels of FGF-23 encountered in terminal renal failure persist after kidney transplantation and may contribute to early post-transplant hypophosphatemia (8–10). It is unclear whether FGF-23 and PTH act alone or together in the development of hypophosphatemia. On the other hand, factors other than PTH and FGF-23 – such as renal function and dietary phosphorus intake – may modulate serum phosphate (sPi) levels (11, 12). This combination of factors was rarely considered in previous studies. We therefore tested the hypothesis that increased FGF-23 levels may be associated with decreased sPi levels and TmPi/GFR, regardless of renal and parathyroid function, dietary phosphate intake and corticosteroid treatment early after renal trans- plantation. We also tested the hypothesis that involve- ment of FGF-23 is mostly limited to a short period after transplantation. European Journal of Endocrinology (2011) 164 839–847 ISSN 0804-4643 q 2011 European Society of Endocrinology DOI: 10.1530/EJE-10-1150 Online version via www.eje-online.org Downloaded from Bioscientifica.com at 10/21/2021 06:08:39PM via free access