title: FGF23-αKlotho as a paradigm for a kidney-bone network.
abstract: The vertebrate endoskeleton is not a mere frame for muscle attachment to facilitate locomotion, but is a massive organ integrated with many physiologic functions including mineral and energy metabolism. Mineral balance is maintained by tightly controlled ion fluxes that are external (intestine and kidney) and internal (between bone and other organs), and are regulated and coordinated by many endocrine signals between these organs. The endocrine fibroblast growth factors (FGFs) and Klotho gene families are complex systems that co-evolved with the endoskeleton. In particular, FGF23 and αKlotho which are primarily derived from bone and kidney respectively, are critical in maintaining mineral metabolism where each of these proteins serving highly diverse roles; abound with many unanswered questions regarding their upstream regulation and downstream functions. Genetic lesions of components of this network produce discreet disturbances in many facets of mineral metabolism. One acquired condition with colossal elevations of FGF23 and suppression of αKlotho is chronic kidney disease where multiple organ dysfunction contributes to the morbidity and mortality. However, the single most important group of derangements that encompasses the largest breadth of complications is mineral metabolism disorders. Mineral metabolic disorders in CKD impact negatively and significantly on the progression of renal disease as well as extra-renal complications. Knowledge of the origin, nature, and impact of phosphate, FGF23, and αKlotho derangements is pivotal to understanding the pathophysiology and treatment of CKD.
authors.affiliation: Center for Molecular Medicine, Jichi Medical University, Tochigi, Japan; Department of Pathology, University of Texas Southwestern Medical Center, Dallas, TX, USA; Charles and Jane Pak Center of Mineral Metabolism and Clinical Research, University of Texas Southwestern Medical Center, Dallas, TX, USA. Electronic address: mkuroo@jichi.ac.jp.
authors.forename: Makoto
authors.initials: M
authors.lastname: Kuro-O
authors.affiliation: Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, USA; Department of Physiology, University of Texas Southwestern Medical Center, Dallas, TX, USA; Charles and Jane Pak Center of Mineral Metabolism and Clinical Research, University of Texas Southwestern Medical Center, Dallas, TX, USA. Electronic address: orson.moe@utsouthwestern.edu.
authors.forename: Orson W
authors.initials: OW
authors.lastname: Moe
mesh_terms: D000818:Animals; D001842:Bone and Bones / Q000378:metabolism* / Q000473:pathology; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000235:genetics / Q000378:metabolism*; D005966:Glucuronidase / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007668:Kidney / Q000378:metabolism* / Q000473:pathology*; D000090265:Klotho Proteins; D051436:Renal Insufficiency, Chronic / Q000378:metabolism* / Q000473:pathology
chemical_list: C000717427:FGF23 protein, human; D005346:Fibroblast Growth Factors; D000089703:Fibroblast Growth Factor-23; D005966:Glucuronidase; D000090265:Klotho Proteins
keywords: Chronic kidney disease; FGF23; Klotho