RT Journal Article SR Electronic T1 Klotho in Clinical Nephrology JF Clinical Journal of the American Society of Nephrology JO CLIN J AM SOC NEPHROL FD American Society of Nephrology SP 162 OP 176 DO 10.2215/CJN.02840320 VO 16 IS 1 A1 Neyra, Javier A. A1 Hu, Ming Chang A1 Moe, Orson W. YR 2021 UL http://cjasn.asnjournals.org/content/16/1/162.abstract AB αKlotho (called Klotho here) is a membrane protein that serves as the coreceptor for the circulating hormone fibroblast growth factor 23 (FGF23). Klotho is also cleaved and released as a circulating substance originating primarily from the kidney and exerts a myriad of housekeeping functions in just about every organ. The vital role of Klotho is shown by the multiorgan failure with genetic deletion in rodents, with certain features reminiscent of human disease. The most common causes of systemic Klotho deficiency are AKI and CKD. Preclinical data on Klotho biology have advanced considerably and demonstrated its potential diagnostic and therapeutic value; however, multiple knowledge gaps exist in the regulation of Klotho expression, release, and metabolism; its target organs; and mechanisms of action. In the translational and clinical fronts, progress has been more modest. Nonetheless, Klotho has potential clinical applications in the diagnosis of AKI and CKD, in prognosis of progression and extrarenal complications, and finally, as replacement therapy for systemic Klotho deficiency. The overall effect of Klotho in clinical nephrology requires further technical advances and additional large prospective human studies.