The phosphatonin pathway: New insights in phosphate homeostasis

Susan C. Schiavi, Rajiv Kumar

Research output: Contribution to journalArticlepeer-review

192 Scopus citations


Serum phosphate concentrations are maintained within a defined range by processes that regulate the intestinal absorption and renal excretion of inorganic phosphate. The hormones currently believed to influence these processes are parathyroid hormone (PTH) and the active metabolite of vitamin D, 1α,25-dihydroxyvitamin D (1α,25(OH)2D). A new class of phosphate-regulating factors, collectively known as the phosphatonins, have been shown to be associated with the hypophosphatemic diseases, tumor-induced osteomalacia (TIO), X-linked hypophosphatemic rickets (XLH), and autosomal-dominant hypophosphatemic rickets (ADHR). These factors, which include fibroblast growth factor 23 (FGF23) and secreted frizzled-related protein 4 (FRP4), decrease extracellular fluid phosphate concentrations by directly reducing renal phosphate reabsorption and by suppressing 1α,25(OH)2D formation through the inhibition of 25-hydroxyvitamin D 1α-hydroxylase. The role of these substances under normal or pathologic conditions is not yet clear. For example, it is unknown whether any of the phosphatonins are directly responsible for the decreased concentrations of 1α,25(OH)2D observed in chronic and end-stage kidney disease or whether they are induced in an attempt to correct the hyperphosphatemia seen in late stages of chronic renal failure. Future experiments should clarify their physiologic and pathologic roles in phosphate metabolism.

Original languageEnglish (US)
Pages (from-to)1-14
Number of pages14
JournalKidney international
Issue number1
StatePublished - Jan 2004


  • Fibroblast growth factor 23 (FGF23)
  • Frizzled related protein 4 (FRP4)
  • Matrix extracellular phosphoglycoprotein (MEPE)
  • Phosphate regulation

ASJC Scopus subject areas

  • Nephrology


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