biostudies-literatureHu MCNIDDK NIH HHSNCRR NIH HHSNHLBI NIH HHS1290-302https://www.ebi.ac.uk/biostudies/studies/S-EPMC4446876biostudies-literatureUnknown26(6)Cardiac dysfunction in CKD is characterized by aberrant cardiac remodeling with hypertrophy and fibrosis. CKD is a state of severe systemic Klotho deficiency, and restoration of Klotho attenuates vascular calcification associated with CKD. We examined the role of Klotho in cardiac remodeling in models of Klotho deficiency-genetic Klotho hypomorphism, high dietary phosphate intake, aging, and CKD. Klotho-deficient mice exhibited cardiac dysfunction and hypertrophy before 12 weeks of age followed by fibrosis. In wild-type mice, the induction of CKD led to severe cardiovascular changes not observed in control mice. Notably, non-CKD mice fed a high-phosphate diet had lower Klotho levels and greatly accelerated cardiac remodeling associated with normal aging compared with those on a normal dietJournal of the American Society of Nephrology : JASNKlotho and phosphate are modulators of pathologic uremic cardiac remodeling.PMC4446876R01-DK091392R01-DK092461R01 DK081374R01-HL080144R01-HL100401P30DK-07938R01 DK076116R01 DK092461U01 HL100401R01 DK091392P30 DK079328R01-DK07611P01 DK020543R01-DK20543S10 RR022584R01 HL080144R01-DK081374K24 DK093723R01-HL0980842P41-RR0022584Shelton JShi MAdams-Huet BHu MCHill JAAmaral APMoe OWPaek JFaul CTaniguchi MCho HJBrand MHill KWolf MTakahashi MKuro-O MfalseKlotho and phosphate are modulators of pathologic uremic cardiac remodeling.Cardiac dysfunction in CKD is characterized by aberrant cardiac remodeling with hypertrophy and fibrosis. CKD is a state of severe systemic Klotho deficiency, and restoration of Klotho attenuates vascular calcification associated with CKD. We examined the role of Klotho in cardiac remodeling in models of Klotho deficiency-genetic Klotho hypomorphism, high dietary phosphate intake, aging, and CKD. Klotho-deficient mice exhibited cardiac dysfunction and hypertrophy before 12 weeks of age followed by fibrosis. In wild-type mice, the induction of CKD led to severe cardiovascular changes not observed in control mice. Notably, non-CKD mice fed a high-phosphate diet had lower Klotho levels and greatly accelerated cardiac remodeling associated with normal aging compared with those on a normal diet2015-01-01T00:00:00Z2015 Jun2025-04-18T17:31:11.362Z2019-03-27T01:52:18ZS-EPMC44468762532658510.1681/asn.201405046510.1681/ASN.2014050465