title: FGF-23 and secondary hyperparathyroidism in chronic kidney disease.
abstract: The metabolic changes that occur in patients with chronic kidney disease (CKD) have a profound influence on mineral and bone metabolism. CKD results in altered levels of serum phosphate, vitamin D, calcium, parathyroid hormone (PTH) and fibroblast growth factor 23 (FGF-23); the increased levels of serum phosphate, PTH and FGF-23 contribute to the increased cardiovascular mortality in affected patients. FGF-23 is produced by osteocytes and osteoblasts and acts physiologically in the kidney to induce phosphaturia and inhibit the synthesis of 1,25-dihydroxyvitamin D3. PTH acts directly on osteocytes to increase FGF-23 expression. In addition, the high levels of PTH associated with CKD contribute to changes in bone remodelling that result in decreased levels of dentin matrix protein 1 and the release of low-molecular-weight fibroblast growth factors from the bone matrix, which stimulate FGF-23 transcription. A prolonged oral phosphorus load increases FGF-23 expression by a mechanism that includes local changes in the ratio of inorganic phosphate to pyrophosphate in bone. Other factors such as dietary vitamin D compounds, calcium, and metabolic acidosis all increase FGF-23 levels. This Review discusses the mechanisms by which secondary hyperparathyroidism associated with CKD stimulates bone cells to overexpress FGF-23 levels.
authors.affiliation: Hadassah Hebrew University Medical Center, Minerva Center for Calcium and Bone Metabolism, Nephrology, Ein Karem, Jerusalem 91120, Israel.
authors.forename: Justin
authors.initials: J
authors.lastname: Silver
authors.forename: Tally
authors.initials: T
authors.lastname: Naveh-Many
mesh_terms: D016723:Bone Remodeling / Q000502:physiology; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000502:physiology*; D006801:Humans; D006962:Hyperparathyroidism, Secondary / Q000209:etiology* / Q000503:physiopathology*; D051436:Renal Insufficiency, Chronic / Q000150:complications* / Q000503:physiopathology*
chemical_list: C000717427:FGF23 protein, human; D005346:Fibroblast Growth Factors; D000089703:Fibroblast Growth Factor-23