A patient with CKD stage 3 has 10 times the likelihood of dying than progression to higher stages of CKD. The number one killer of patients with CKD far in excess of another cause is cardiovascular disease. The conventional Framingham risk factors ony has a minor contribution to this dire complication. Uremic cardiomyopathy is a metabolic disease caused by the uremic milieu which is composed of a very wide myriad of factors. Three such intermediates are excess FGF23 and phosphate, and deficiency in aKlotho. Our laboratory uses animal interventional and human observational studies to test therapeutic regimens to alleviate uremic cardiomyopathy, and stem cell-derived cardiomyocyte cellular studies to unravel the molecular mechanisms of how this triad of disturbances affect cardiac cell function.