FGF23 and chronic kidney disease: In this study, we demonstrate that: (1) CKD upregulates FGF23 level and exacerbates Klotho insufficiency in aortic valves of old mice, leading to aortic valve lesions; (2) FGF23 elevates the pathobiological activities, including inflammatory, fibrogenic and osteogenic activities, in human AVICs through the FGFR-YAP signaling pathway; (3) soluble Klotho suppresses the effect of FGF23 on AVIC pathobiological activities through molecular interaction with FGF23; and (4) recombinant Klotho is capable of reducing aortic valve lesions.