Effect of Dapagliflozin on Metabolomics and Cardiac Mechanics in Chronic Kidney Disease

Inclusion Criteria: >18 years of age eGFR 25-60 ml/min/1,73m2 (eGFR = estimated glomerular filtration rate) On stable doses of diuretics and/or angiotensin converting enzyme inhibitor or angiotensin receptor blocker Evidence of subclinical heart failure with preserved ejection fraction at their pre-exercise echocardiogram (defined as meeting any of the American Society of Echocardiography (ASE) criteria for diastolic dysfunction [septal e'<7 cm/wc, average E/e' ratio>14, left atrial volume index >34 mL/m2, and peak TR velocity >2.8 m/sec] or absolute left ventricular longitudinal strain < 18%) Exclusion Criteria: presence or history of diabetes coronary revascularization within the last 6 months hemodynamically significant valvular disease significant lung disease requiring home oxygen angina (chest pain) non-revascularized myocardial ischemia systolic BP <100 or >180 mmHg pregnancy clinical heart failure symptoms history of systemic disease processes that can cause HFpEF such as amyloidosis or sarcoidosis any musculoskeletal or chronic condition that will interfere with completion of cardiac testing active cancer immunosuppressive therapy baseline or pre-exercise echocardiogram demonstrates a reduced ejection fraction </= 50% currently on sodium glucose cotransporter 2 inhibitor (SGLT2i) therapy Hypersensitivity to a SGLT2i Pre-existing liver disease ALT/AST> 3x normal (ALT = alanine aminotransferase AST = aspartate aminotransferase) history of recurrent urinary tract infections (in the opinion of the investigator) or a urinary tract infection in the last 3 months