Fibroblast growth factor 23 and klotho: Physiology and pathophysiology of an endocrine network of mineral metabolism

Ming C Hu, Kazuhiro Shiizaki, Makoto Kuro-o, Orson W Moe

Research output: Contribution to journalArticle

266 Scopus citations


The metabolically active and perpetually remodeling calcium phosphate-based endoskeleton in terrestrial vertebrates sets the demands on whole-organism calcium and phosphate homeostasis that involves multiple organs in terms of mineral flux and endocrine cross talk. The fibroblast growth factor (FGF)-Klotho endocrine networks epitomize the complexity of systems biology, and specifically, the FGF23-αKlotho axis highlights the concept of the skeleton holding the master switch of homeostasis rather than a passive target organ as hitherto conceived. Other than serving as a coreceptor for FGF23, αKlotho circulates as an endocrine substance with a multitude of effects. This review covers recent data on the physiological regulation and function of the complex FGF23-αKlotho network. Chronic kidney disease is a common pathophysiological state in which FGF23-αKlotho, a multiorgan endocrine network, is deranged in a self-amplifying vortex resulting in organ dysfunction of the utmost severity that contributes to its morbidity and mortality.

Original languageEnglish (US)
Pages (from-to)503-533
Number of pages31
JournalAnnual Review of Physiology
Publication statusPublished - Feb 10 2013



  • Bone
  • Calcium
  • FGF23
  • Kidney
  • Klotho
  • Phosphate

ASJC Scopus subject areas

  • Physiology

Cite this