TY - JOUR
T1 - Post-transplant hypophosphatemia
T2 - Tertiary 'Hyper-Phosphatoninism'?
AU - Bhan, I.
AU - Shah, A.
AU - Holmes, J.
AU - Isakova, T.
AU - Gutierrez, O.
AU - Burnett, S. A.
AU - Jüppner, H.
AU - Wolf, M.
N1 - Funding Information:
This work was supported by a Young Investigator Grant from the National Kidney Foundation (MW), and Grants K23RR017376 (MW) and M01RR01066 (Massachusetts General Hospital General Clinical Research Center) from the National Center for Research Resources, National Institutes of Health.
PY - 2006/10
Y1 - 2006/10
N2 - Hypophosphatemia is a common complication of kidney transplantation. Tertiary hyperparathyroidism has long been thought to be the etiology, but hypophosphatemia can occur despite low parathyroid hormone (PTH) levels and can persist after high PTH levels normalize. Furthermore, even in the setting of normal allograft function, hypophosphatemia, and hyperparathyroidism, calcitriol levels remain inappropriately low following transplantation, suggesting that mechanisms other than PTH contribute. Fibroblast growth factor-23 (FGF-23) induces phosphaturia, inhibits calcitriol synthesis, and accumulates in chronic kidney disease. We performed a prospective, longitudinal study of 27 living donor transplant recipients to test the hypotheses that excessive FGF-23 accounts for hypophosphatemia and decreased calcitriol levels following kidney transplantation. Hypophosphatemia <2.5 mg/dl developed in 85% of subjects, including one who had previously undergone parathyroidectomy; 37% developed phosphate ≤1.5 mg/dl. The mean pre-transplant FGF-23 level was 1,218±542 RU/ml. Within the first week following transplantation, mean levels decreased to 557±579 RU/ml, which were still above normal. FGF-23 was independently associated with serum phosphate (P<0.01), urinary excretion of phosphate (P<0.01), and calcitriol levels (P<0.01); PTH was not independently associated with any of these parameters. We calculated area under the curve for FGF-23 and PTH between the pre- and first post-transplant levels as a summary measure of early exposure to these phosphaturic hormones. An area under the FGF-23 curve greater than the median was associated with a relative risk of developing hypophosphatemia ≤1.5 mg/dl of 5.3 (P=0.02) compared with lower levels. Increased area under the PTH curve was not associated with greater risk of hypophosphatemia. Excessive FGF-23 exposure in the early post-transplant period appears to be more strongly associated with post-transplant hypophosphatemia than PTH.
AB - Hypophosphatemia is a common complication of kidney transplantation. Tertiary hyperparathyroidism has long been thought to be the etiology, but hypophosphatemia can occur despite low parathyroid hormone (PTH) levels and can persist after high PTH levels normalize. Furthermore, even in the setting of normal allograft function, hypophosphatemia, and hyperparathyroidism, calcitriol levels remain inappropriately low following transplantation, suggesting that mechanisms other than PTH contribute. Fibroblast growth factor-23 (FGF-23) induces phosphaturia, inhibits calcitriol synthesis, and accumulates in chronic kidney disease. We performed a prospective, longitudinal study of 27 living donor transplant recipients to test the hypotheses that excessive FGF-23 accounts for hypophosphatemia and decreased calcitriol levels following kidney transplantation. Hypophosphatemia <2.5 mg/dl developed in 85% of subjects, including one who had previously undergone parathyroidectomy; 37% developed phosphate ≤1.5 mg/dl. The mean pre-transplant FGF-23 level was 1,218±542 RU/ml. Within the first week following transplantation, mean levels decreased to 557±579 RU/ml, which were still above normal. FGF-23 was independently associated with serum phosphate (P<0.01), urinary excretion of phosphate (P<0.01), and calcitriol levels (P<0.01); PTH was not independently associated with any of these parameters. We calculated area under the curve for FGF-23 and PTH between the pre- and first post-transplant levels as a summary measure of early exposure to these phosphaturic hormones. An area under the FGF-23 curve greater than the median was associated with a relative risk of developing hypophosphatemia ≤1.5 mg/dl of 5.3 (P=0.02) compared with lower levels. Increased area under the PTH curve was not associated with greater risk of hypophosphatemia. Excessive FGF-23 exposure in the early post-transplant period appears to be more strongly associated with post-transplant hypophosphatemia than PTH.
KW - Calcitriol
KW - FGF-23
KW - Hypophosphatemia
KW - PTH
KW - Transplantation
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U2 - 10.1038/sj.ki.5001788
DO - 10.1038/sj.ki.5001788
M3 - Article
C2 - 16941023
AN - SCOPUS:33749508711
VL - 70
SP - 1486
EP - 1494
JO - Kidney International
JF - Kidney International
SN - 0085-2538
IS - 8
ER -