title: Potential application of klotho in human chronic kidney disease.
abstract: The extracellular domain of transmembrane alpha-Klotho (αKlotho, hereinafter simply called Klotho) is cleaved by secretases and released into the circulation as soluble Klotho. Soluble Klotho in the circulation starts to decline early in chronic kidney disease (CKD) stage 2 and urinary Klotho possibly even earlier in CKD stage 1. Therefore soluble Klotho could serve as an early and sensitive marker of kidney function decline. Moreover, preclinical animal data support Klotho deficiency is not just merely a biomarker, but a pathogenic factor for CKD progression and extrarenal CKD complications including cardiovascular disease and disturbed mineral metabolism. Prevention of Klotho decline, re-activation of endogenous Klotho production or supplementation of exogenous Klotho are all associated with attenuation of renal fibrosis, retardation of CKD progression, improvement of mineral metabolism, amelioration of cardiomyopathy, and alleviation of vascular calcification in CKD. Therefore Klotho is not only a diagnostic and/or prognostic marker for CKD, but the treatment of Klotho deficiency may be a promising strategy to prevent, retard, and decrease the burden of comorbidity in CKD.
authors.affiliation: Department of Internal Medicine, University of Texas Southwestern Medical Center, USA; Charles and Jane Pak Center for Mineral Metabolism and Clinical Research, University of Texas Southwestern Medical Center, USA.
authors.forename: Javier A
authors.initials: JA
authors.lastname: Neyra
authors.affiliation: Department of Internal Medicine, University of Texas Southwestern Medical Center, USA; Charles and Jane Pak Center for Mineral Metabolism and Clinical Research, University of Texas Southwestern Medical Center, USA. Electronic address: ming-chang.hu@utsouthwestern.edu.
authors.forename: Ming Chang
authors.initials: MC
authors.lastname: Hu
mesh_terms: D009202:Cardiomyopathies / Q000097:blood / Q000378:metabolism; D005966:Glucuronidase / Q000378:metabolism*; D006801:Humans; D000090265:Klotho Proteins; D051436:Renal Insufficiency, Chronic / Q000097:blood / Q000378:metabolism*; D014807:Vitamin D / Q000097:blood / Q000378:metabolism
chemical_list: D014807:Vitamin D; D005966:Glucuronidase; D000090265:Klotho Proteins
keywords: AKI; CKD; Klotho; Phosphate; Uremic cardiomyopathy; Vascular calcification; Vitamin D