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Fibroblast growth factor 23 and phosphate homeostasis

Balani, Shanthi; Perwad, Farzana

Current Opinion in Nephrology and Hypertension: September 2019 - Volume 28 - Issue 5 - p 465–473
doi: 10.1097/MNH.0000000000000526
MOLECULAR CELL BIOLOGY AND PHYSIOLOGY OF SOLUTE TRANSPORT: Edited by Vivek Bhalla and Alan C. Pao
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Purpose of review The 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 findings Recent 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.

Summary Significant 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.

Division of Nephrology, Department of Pediatrics, University of California, San Francisco, San Francisco, California, USA

Correspondence to Farzana Perwad, MD, Division of Nephrology, Department of Pediatrics, University of California, San Francisco, 550 16th Street, San Francisco, CA 94158, USA. Tel: +1 415 476 2423; fax: +1 415 476 9976; e-mail: Farzana.perwad@ucsf.edu

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