title: Fibroblast growth factor 23 actions in inflammation: a key factor in CKD outcomes.
abstract: During chronic kidney disease (CKD), bone mineral metabolism is disturbed owing in part to the endogenous hormone fibroblast growth factor 23 (FGF23). Elevated FGF23 levels are seen in CKD patients. Current research has demonstrated that FGF23 directly modulates the immune response and host defense to bacterial infections. FGF23 also impairs the activation and recruitment of neutrophils, which are the main immune effector cells required for host defense against bacterial infections. In addition, while FGF23 levels reduce leukocyte recruitment and functions, inflammatory conditions may also-in a reverse fashion-contribute to elevated FGF23 levels in the circulation. In this context, altered hypoxia inducible factor 1α signaling and iron metabolism may contribute to intact FGF23 (iFGF23) production. This review examines evidence on the role of FGF23 in inflammation, immune cell function and recruitment as well as the regulation of FGF23 during inflammation and the clinical implications of this process for the immune system in individuals with CKD. Clinical observations and laboratory investigations indicate an important role of FGF23 in directly modulating leukocyte activation and recruitment behavior with consequences on host defense against bacterial infections. This novel observation may in part explain the increased infectious risk among patients with CKD. However, studies of FGF23 neutralization also revealed increased mortality after sustained administration over several weeks in rats. Thus, therapeutic interventions targeting FGF23 must be carefully evaluated.
authors.affiliation: Department of Anaesthesiology, Intensive Care and Pain Medicine, University Hospital Münster, Münster, Germany.
authors.forename: Jan
authors.initials: J
authors.lastname: Rossaint
authors.affiliation: Division of Nephrology, Department of Internal Medicine, University of New Mexico School of Medicine, Albuquerque, NM, USA.|Section of Neprology, New Mexico Veteran Affairs Hospital, Albuquerque, NM, USA.
authors.forename: Mark
authors.initials: M
authors.lastname: Unruh
authors.affiliation: Department of Anaesthesiology, Intensive Care and Pain Medicine, University Hospital Münster, Münster, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Zarbock
mesh_terms: D000818:Animals; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000378:metabolism*; D006801:Humans; D007249:Inflammation / Q000378:metabolism / Q000503:physiopathology*; D051381:Rats; D051436:Renal Insufficiency, Chronic / Q000378:metabolism / Q000503:physiopathology*
chemical_list: C000717427:FGF23 protein, human; D005346:Fibroblast Growth Factors; D000089703:Fibroblast Growth Factor-23
keywords: CKD; FGF23; inflammation; neutrophils