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Kidney Int. 2012 Oct;82(7):737-47. doi: 10.1038/ki.2012.176. Epub 2012 May 23.

Update on fibroblast growth factor 23 in chronic kidney disease.

Author information

1
Department of Medicine, Division of Nephrology and Hypertension, University of Miami Miller School of Medicine, Miami, Florida 33136, USA.

Abstract

Chronic kidney disease (CKD) is a public health epidemic that affects millions of people worldwide. Presence of CKD predisposes individuals to high risks of end-stage renal disease (ESRD), cardiovascular disease, and premature death. Disordered phosphate homeostasis with elevated circulating levels of fibroblast growth factor 23 (FGF23) is an early and pervasive complication of CKD. CKD is likely the most common cause of chronically elevated FGF23 levels, and the clinical condition in which levels are most markedly elevated. Although increases in FGF23 levels help maintain serum phosphate in the normal range in CKD, prospective studies in populations of pre-dialysis CKD, incident and prevalent ESRD, and kidney transplant recipients demonstrate that elevated FGF23 levels are independently associated with progression of CKD and development of cardiovascular events and mortality. It was originally thought that these observations were driven by elevated FGF23 levels acting as a highly sensitive biomarker of toxicity due to phosphate. However, FGF23 itself has now been shown to mediate 'off-target,' direct, end-organ toxicity in the heart, which suggests that elevated FGF23 levels may be a novel mechanism of adverse outcomes in CKD. This report reviews recent advances in FGF23 biology relevant to CKD, the classical effects of FGF23 on mineral homeostasis, and the studies that established FGF23 excess as a biomarker and novel mechanism of cardiovascular disease. The report concludes with a critical review of the effects of different therapeutic strategies targeting FGF23 reduction and how these might be leveraged in a future randomized trial aimed at improving outcomes in CKD.

PMID:
22622492
PMCID:
PMC3434320
DOI:
10.1038/ki.2012.176
[Indexed for MEDLINE]
Free PMC Article

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