FGF-23 and secondary hyperparathyroidism in chronic kidney disease

Nat Rev Nephrol. 2013 Nov;9(11):641-9. doi: 10.1038/nrneph.2013.147. Epub 2013 Jul 23.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Bone Remodeling / physiology
  • Fibroblast Growth Factors / physiology*
  • Humans
  • Hyperparathyroidism, Secondary / etiology*
  • Hyperparathyroidism, Secondary / physiopathology*
  • Renal Insufficiency, Chronic / complications*
  • Renal Insufficiency, Chronic / physiopathology*

Substances

  • Fibroblast Growth Factors
  • fibroblast growth factor 23