KL and cardiac hypertrophy: Likewise, klotho hypomorphic mice develop severe cardiac hypertrophy and fibrosis with activation of the calcineurin/NFAT and TGF-β signaling pathways (Faul et al., 2011; Leifheit-Nestler et al., 2018b), and heterozygous klotho-deficient mice show decreased EF, SV, cardiac output, and impaired cardiac geometry (Hu et al., 2015).