Mechanism by which Klotho deficiency aggravated cardiomyopathy in the setting of renal dysfunction is unknown, but it might be related to the observation that soluble Klotho inhibits stress-induced cardiac TRPC6 expression and activation of NFAT [34], which in turn may induce fetal gene expression and pathologic cardiac hypertrophy and remodeling [35]. Here, KL is linked to cardiac hypertrophy.