KL and chronic kidney disease: In humans, circulating levels of soluble Klotho decrease with age (Xiao et al., 2004), and emerging evidence suggests that Klotho concentration is closely correlated to the development of cardiovascular disease (Semba et al., 2011; Hu et al., 2013) and chronic kidney disease (CKD) (Akimoto et al., 2012; Asai et al., 2012).