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Phosphate and FGF-23 homeostasis after kidney transplantation

Nature Reviews Nephrology volume 11, pages 656–666 (2015)Cite this article

Subjects

Key Points

  • Abnormalities in phosphate homeostasis are common in renal transplant recipients, ranging from hypophosphataemia within 3 months after transplantation to hyperphosphataemia, hyperparathyroidism, and high FGF-23 levels in the late post-transplantation stage

  • Persistent high levels of FGF-23 and parathyroid hormone during the first months post-transplantation, and the influence of immunosuppressive drugs, ischaemia–reperfusion injury, and metabolic acidosis, can result in post-transplantation hypophosphataemia

  • Long-term exposure to high levels of phosphate and FGF-23 might have distinct yet associated adverse effects on the cardiovascular system, kidney, and bone in renal transplant recipients

  • Although data are limited, renal transplant recipients might benefit from dietary and pharmacologic interventions to improve phosphate metabolism; future studies should address whether these measures can improve cardiorenal prognosis

Abstract

Dysregulated phosphate metabolism is a common consequence of chronic kidney disease, and is characterized by a high circulating level of fibroblast growth factor (FGF)-23, hyperparathyroidism, and hyperphosphataemia. Kidney transplantation can elicit specific alterations to phosphate metabolism that evolve over time, ranging from severe hypophosphataemia (<0.5 mmol/l) to hyperphosphataemia (>1.50 mmol/l) and high FGF-23 levels. The majority of renal transplant recipients develop hypophosphataemia during the first 3 months after transplantation as a consequence of relatively slow adaptation of FGF-23 and parathyroid hormone levels to restored renal function, and the influence of immunosuppressive drugs. By 3–12 months after transplantation, phosphate homeostasis is at least partially restored in the majority of recipients, which is paralleled by a substantially reduced risk of cardiovascular-associated morbidity and mortality compared with the pre-transplantation setting. Many renal transplant recipients, however, exhibit persistent abnormalities in phosphate homeostasis, which is often due to multifactorial causes, and may contribute to adverse outcomes on the cardiovascular system, kidney, and bone. Dietary and pharmacologic interventions might improve phosphate homeostasis in renal transplant recipients, but additional insight into the pathophysiology of transplantation-associated abnormalities in phosphate homeostasis is needed to further optimize disease management and improve prognosis for renal transplant recipients.

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Figure 1: Graphical overview of the hypothetical course of serum phosphate, parathyroid hormone (PTH), and FGF-23 levels in patients with CKD undergoing kidney transplantation.
Figure 2: Phosphate transport in enterocytes and renal proximal tubular epithelial cells.
Figure 3: Development of hypophosphataemia and hyperphosphataemia after kidney transplantation.

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Acknowledgements

G.N. and M.H.d.B. participate in the NIGRAM consortium, which is supported by a grant from the Dutch Kidney Foundation (grant number CP10.11). The NIGRAM consortium consists of the following principal investigators: Pietter Wee, Marc Vervloet (VU University Medical Centre, Amsterdam, Netherlands), René Bindels, Joost Hoenderop (Radboud University Medical Centre Nijmegen, the Netherlands), Gerjan Navis, Jan-Luuk Hillebrands and Martin de Borst (University Medical Centre Groningen, the Netherlands). The research of M.H.d.B. is supported by a grant from the Netherlands Organization for Scientific Research (Veni grant).

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  1. Division of Nephrology, Department of Medicine, Universidade Federal de São Paulo, Rua Botucatu 740—Vila Clementino, São Paulo, 04023 900, SP, Brazil

    Leandro C. Baia & Ita Pfeferman Heilberg

  2. Division of Nephrology, Department of Internal Medicine, University of Groningen, University Medical Centre Groningen, Hanzeplein 1, PO Box 30.001, Groningen, 9700 RB, Netherlands

    Gerjan Navis & Martin H. de Borst

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All authors researched the data for the article, provided a substantial contribution to discussions of the content, and contributed equally to writing the article and to review and/or editing of the manuscript before submission.

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Correspondence to Gerjan Navis or Martin H. de Borst.

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Baia, L., Heilberg, I., Navis, G. et al. Phosphate and FGF-23 homeostasis after kidney transplantation. Nat Rev Nephrol 11, 656–666 (2015). https://doi.org/10.1038/nrneph.2015.153

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