title: New insights into the FGF23-Klotho axis.
abstract: Abnormal mineral metabolism is a hallmark in patients with advanced chronic kidney disease (CKD). Hyperphosphatemia, and the homeostatic mechanisms controlling phosphate metabolism, have received particular attention over the past decade. The phosphate-regulating hormone fibroblast growth factor-23 (FGF23) was discovered through studies of rare hypophosphatemic disorders, whereas Klotho, which subsequently turned out to be a co-receptor for FGF23, was identified in a mouse model showing hyperphosphatemia and multiple aging-like traits. The FGF23-Klotho endocrine axis is a pivotal regulator of mineral metabolism. In CKD, early onset of Klotho deficiency contributes to renal FGF23 resistance and a maladaptive increase in circulating FGF23. FGF23 is an early biomarker of renal injury and increased FGF23 predicts adverse clinical outcomes, in particular cardiovascular disease. A paradigm of FGF23 excess and Klotho deficiency is proposed, in which FGF23 preferentially stimulates left ventricular hypertrophy, and loss of Klotho augments fibrosis, endothelial dysfunction, and vascular calcification. The clinical benefit of FGF23 and Klotho measurements remain uncertain, nevertheless, the FGF23-Klotho axis is a solid candidate for a novel diagnostic and therapeutic target in CKD.
authors.affiliation: Division of Renal Medicine, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Hannes
authors.initials: H
authors.lastname: Olauson
authors.affiliation: Department of Nephrology, Institute for Cardiovascular Research, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Marc G
authors.initials: MG
authors.lastname: Vervloet
authors.affiliation: Department of Health Sciences, University of Milan, Renal Division, San Paolo Hospital, Milan, Italy.
authors.forename: Mario
authors.initials: M
authors.lastname: Cozzolino
authors.affiliation: Inserm U-1088, Université de Picardie Jules Verne (UPJV), Amiens, France; Division of Nephrology, Ambroise Paré Hospital, Paris-Ile-de-France-Ouest University (Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)), Paris-Boulogne Billancourt, France.
authors.forename: Ziad A
authors.initials: ZA
authors.lastname: Massy
authors.affiliation: Service of Nephrology and Dialysis, Clinique du Landy and Department of Renal Physiology, Necker Hospital, University of Paris Descartes, Paris, France.
authors.forename: Pablo
authors.initials: P
authors.lastname: Ureña Torres
authors.affiliation: Division of Renal Medicine, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden; Department of Nephrology, Karolinska University Hospital, Stockholm, Sweden. Electronic address: tobias.larsson@ki.se.
authors.forename: Tobias E
authors.initials: TE
authors.lastname: Larsson
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000097:blood; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D005966:Glucuronidase / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D006962:Hyperparathyroidism, Secondary / Q000209:etiology / Q000378:metabolism; D000090265:Klotho Proteins; D010710:Phosphates / Q000378:metabolism; D051436:Renal Insufficiency, Chronic / Q000150:complications / Q000378:metabolism*
chemical_list: D015415:Biomarkers; C000717427:FGF23 protein, human; C000717428:Fgf23 protein, mouse; D010710:Phosphates; D005346:Fibroblast Growth Factors; D000089703:Fibroblast Growth Factor-23; D005966:Glucuronidase; D000090265:Klotho Proteins
keywords: FGF-23; Fibroblast growth factor-23; calcium; chronic kidney disease; parathyroid hormone; phosphate; vitamin D