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  • Review Article
  • Published:

Recent advances in renal phosphate handling

Nature Reviews Nephrology volume 6, pages 207–217 (2010)Cite this article

Subjects

Abstract

Phosphate is critical for the maintenance of skeletal integrity, is a necessary component of important biomolecules, and is central to signal transduction and cell metabolism. It is becoming clear that endocrine communication between the skeleton, kidney, and the intestine is involved in maintaining appropriate serum phosphate concentrations, and that the kidney is the primary site for minute-to-minute regulation of phosphate levels. The identification of genetic alterations in Mendelian disorders of hypophosphatemia and hyperphosphatemia has led to the isolation of novel genes and the identification of new roles for existing proteins—such as fibroblast growth factor 23 and its processing systems, the co-receptor α-klotho, and phosphate transporters—in the control of renal phosphate handling. Recent findings also indicate that fibroblast growth factor 23 has feedback mechanisms involving parathyroid hormone and vitamin D that control phosphate homeostasis. This Review will highlight genetic, in vitro and in vivo findings, and will discuss how these clinical and experimental discoveries have uncovered novel aspects of renal phosphate handling and opened new research and therapeutic avenues.

Key Points

  • Fibroblast growth factor 23 (FGF23) is a phosphaturic hormone produced in bone

  • FGF23 and parathyroid hormone (PTH) decrease the expression of the sodium–phosphate co-transporters Npt2a and Npt2c

  • FGF23 and PTH have opposing effects on 1,25-dihydroxyvitamin D, with FGF23 suppressing its production, and PTH increasing its production

  • The actions of FGF23 in the kidney are dependent on the expression of the co-receptor klotho, but the mechanisms guiding FGF23-dependent signaling may be complex

  • Human disorders associated with increased circulating concentrations of FGF23 are characterized by hypophosphatemia, and disorders associated with reduced FGF23 bioactivity are characterized by hyperphosphatemia

  • FGF23 and its receptor systems are promising targets for targeted therapeutics in the treatment of both heritable and acquired disorders of phosphate handling

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Figure 1: FGF23 regulatory systems in phosphate metabolism.
Figure 2: The molecular and physiological consequences of genetic alterations in heritable hypophosphatemia and hyperphosphatemia.

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Acknowledgements

The authors would like to acknowledge support from NIH grant DK063934 (K. E. White), the Showalter Foundation, Genzyme Corporation, and the Indiana Genomics Initiative (INGEN) of Indiana University, supported in part by the Lilly Endowment. The authors would also like to acknowledge the editorial and scientific contributions of Ms L. J. Summers, Indiana University School of Medicine, Indianapolis, IN, USA.

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  1. Department of Medical & Molecular Genetics, Indiana University School of Medicine, 975 West Walnut Street, Indianapolis, 46202, IN, USA

    Emily G. Farrow & Kenneth E. White

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  1. Emily G. Farrow
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Correspondence to Kenneth E. White.

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Competing interests

K. E. White declares associations with the following companies: Genzyme (grant/research support), Kyowa Hakko Kirin (royalties for licensing the FGF23 gene). E. G. Farrow declares no competing interests.

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Farrow, E., White, K. Recent advances in renal phosphate handling. Nat Rev Nephrol 6, 207–217 (2010). https://doi.org/10.1038/nrneph.2010.17

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