Fibroblast growth factor 23 and phosphate homeostasis

Shanthi Balani, Farzana Perwad

Research output: Contribution to journalReview articlepeer-review

16 Scopus citations


Purpose of reviewThe current review highlights recent advances in the area of renal tubular phosphate transport and its regulation by fibroblast growth factor 23 (FGF23), a potent regulator of phosphate homeostasis.Recent findingsRecent studies demonstrate that FGF23 binds to both membrane and soluble form of α-klotho to activate FGF receptor signaling pathways. Parathyroid hormone and FGF23 equivalently decrease sodium-dependent phosphate cotransport but the effect is not additive, suggesting a shared but not synergistic mechanism of action. Crosstalk occurs downstream of parathyroid hormone-receptor and FGF23-receptor signaling and converge at the level of the scaffolding protein, sodium-hydrogen exchanger regulatory factor-1. A novel mechanism for phosphate efflux through the basolateral membrane of renal proximal tubular epithelia via an atypical G-protein coupled receptor, Xenotropic and polytropic retrovirus receptor 1 (XPR1), was recently identified. Conditional deletion of Xpr1 gene in renal proximal tubules in mice leads to hypophosphatemic rickets and Fanconi syndrome establishing an important role for XPR1 in phosphate homeostasis. A novel anti-FGF23 antibody, burosumab, was recently approved to treat X-linked hypophosphatemia, a human disorder of FGF23 excess.SummarySignificant advances in understanding the cellular and molecular aspects of renal tubular phosphate transport and its regulation by FGF23 has led to the discovery of novel therapeutics to treat human disorders of phosphate homeostasis.

Original languageEnglish (US)
Pages (from-to)465-473
Number of pages9
JournalCurrent opinion in nephrology and hypertension
Issue number5
StatePublished - Sep 1 2019
Externally publishedYes

Bibliographical note

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© 2019 Wolters Kluwer Health, Inc. All rights reserved.


  • fibroblast growth factor 23
  • homeostasis
  • kidney
  • phosphate transport
  • proximal tubule


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