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: Justin Silver, Tally Naveh-Many
• Journal: Nature reviews. Nephrology (Nat Rev Nephrol) Vol. 9 Issue 11 Pg. 641-9 (Nov 2013) ISSN: 1759-507X [Electronic] England
• PMID: 23877588 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)

Chemical References

• FGF23 protein, human
• Fibroblast Growth Factors
• Fibroblast Growth Factor-23

Topics

• Bone Remodeling (physiology)
• Fibroblast Growth Factor-23
• Fibroblast Growth Factors (physiology)
• Humans
• Hyperparathyroidism, Secondary (etiology, physiopathology)
• Renal Insufficiency, Chronic (complications, physiopathology)