Role of fibroblast growth factor 23 in phosphate homeostasis and pathogenesis of disordered mineral metabolism in chronic kidney disease.
The discovery of fibroblast growth factor 23 (FGF23), a novel bone-derived hormone that inhibits phosphate reabsorption and calcitriol production by the kidney, has uncovered primary regulatory pathways and new systems biology governing bone mineralization, vitamin D metabolism, parathyroid gland function and renal phosphate handling. This phosphaturic hormone, which is made predominately by osteocytes in bone, appears to have a physiologic role as a counter-regulatory hormone for vitamin D. Evidence has also emerged to support the existence of a bone-kidney axis to coordinate the mineralization of bone with renal handling of phosphate. Pathologically, high circulating levels of FGF23 result in hypophosphatemia, decreased production of 1,25(OH)(2)D, elevated parathyroid hormone and rickets/osteomalacia in patients with functioning kidneys, whereas low levels are associated with tumoral calcinosis, hyperphosphatemia and elevated 1,25(OH)(2)D. In addition, patients with chronic kidney disease (CKD) exhibit marked elevations of circulating FGF23. While the significance of increased FGF23 levels in CKD remains to be defined, it might contribute to phosphate excretion and suppression of 1,25(OH)(2)D levels in CKD stages 3 and 4, as well as potentially contribute to secondary hyperparathyroidism through direct actions on the parathyroid gland in more advanced renal failure. As our knowledge expands regarding the regulation and functions of FGF23, the assessment of FGF23 will become an important diagnostic marker as well as a therapeutic target for management of disordered mineral metabolism in a variety of acquired and hereditary disorders.
Stubbs
Jason
J
The Kidney Institute, University of Kansas Medical Center, Kansas City, Kansas 66160, USA.
Liu
Shiguang
S
Quarles
L Darryl
LD
D000818:Animals; D001842:Bone and Bones / Q000378:metabolism / Q000502:physiology*; D002118:Calcium / Q000502:physiology; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000502:physiology*; D006706:Homeostasis / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D007668:Kidney / Q000502:physiology*; D007676:Kidney Failure, Chronic / Q000150:complications / Q000378:metabolism* / Q000503:physiopathology*; D010281:Parathyroid Hormone / Q000502:physiology; D010758:Phosphorus / Q000378:metabolism*; D010760:Phosphorus Metabolism Disorders / Q000209:etiology / Q000235:genetics / Q000503:physiopathology*; D017468:Receptors, Fibroblast Growth Factor / Q000502:physiology; D014807:Vitamin D / Q000502:physiology
C000717427:FGF23 protein, human; D010281:Parathyroid Hormone; D017468:Receptors, Fibroblast Growth Factor; D014807:Vitamin D; D010758:Phosphorus; D005346:Fibroblast Growth Factors; D000089703:Fibroblast Growth Factor-23; D002118:Calcium