The role of FGF23 in CKD--with or without Klotho.

Abstract

During the past few years, fibroblast growth factor 23 (FGF23) has emerged as a central player of disordered mineral metabolism in patients with chronic kidney disease (CKD). The physiological actions of FGF23 are to promote phosphaturia, decrease production of 1,25-dihydroxyvitamin D and suppress secretion of parathyroid hormone mediated through FGF receptors and the co-receptor Klotho. Recent epidemiological studies demonstrate strong associations between elevated FGF23 levels in patients with CKD and poor clinical outcomes. In patients with end-stage renal disease, markedly increased levels of FGF23 fail to exert Klotho-dependent effects owing to the absence of a functioning kidney and downregulation of the parathyroid complex of Klotho and FGF receptor 1. In this setting, FGF23 may exert a toxic effect on the cardiovascular system in a Klotho-independent manner. Future research should examine whether treatment to attenuate the pathogenic action of FGF23 provides survival benefits in patients with CKD.

• Authors: Hirotaka Komaba, Masafumi Fukagawa
• Journal: Nature reviews. Nephrology (Nat Rev Nephrol) Vol. 8 Issue 8 Pg. 484-90 (Jun 19 2012) ISSN: 1759-507X [Electronic] England
• PMID: 22714041 (Publication Type: Journal Article, Review)

Chemical References

• Biomarkers
• FGF23 protein, human
• Parathyroid Hormone
• Fibroblast Growth Factors
• Fibroblast Growth Factor-23
• Glucuronidase
• Klotho Proteins

Topics

• Biomarkers
• Bone Diseases (metabolism)
• Fibroblast Growth Factor-23
• Fibroblast Growth Factors (physiology)
• Glucuronidase (metabolism)
• Humans
• Hyperparathyroidism, Secondary (etiology)
• Kidney Failure, Chronic (metabolism)
• Klotho Proteins
• Parathyroid Hormone (blood)
• Renal Insufficiency, Chronic (metabolism)