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

Inclusion Criteria: 1. \>18 years of age 2. eGFR 25-60 ml/min/1,73m2 (eGFR = estimated glomerular filtration rate) 3. On stable doses of diuretics and/or angiotensin converting enzyme inhibitor or angiotensin receptor blocker 4. Evidence of subclinical heart failure with preserved ejection fraction at their pre-exercise echocardiogram (defined as meeting 3/5 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%, left atrial reservoir strain (LARS) \< 25% on 2d speckle tracking echocardiography), lack of augmentation of LVLS or LARS during exercise, or peak VO2 Females: ≤ 18 mL/kg/min, peak VO2 Males: ≤ 20 mL/kg/min on cardiopulmonary exercise testing. Exclusion Criteria: 1. presence or history of diabetes 2. coronary revascularization within the last 6 months 3. hemodynamically significant valvular disease 4. significant lung disease requiring home oxygen 5. angina (chest pain) 6. non-revascularized myocardial ischemia 7. systolic BP \<100 or \>180 mmHg 8. pregnancy 9. clinical heart failure symptoms 10. history of systemic disease processes that can cause HFpEF such as amyloidosis or sarcoidosis 11. any musculoskeletal or chronic condition that will interfere with completion of cardiac testing 12. active cancer 13. immunosuppressive therapy 14. baseline or pre-exercise echocardiogram demonstrates a reduced ejection fraction \< 50% 15. currently on sodium glucose cotransporter 2 inhibitor (SGLT2i) therapy 16. Hypersensitivity to a SGLT2i 17. Pre-existing liver disease 18. ALT/AST\> 3x normal (ALT = alanine aminotransferase AST = aspartate aminotransferase) 19. history of recurrent urinary tract infections (in the opinion of the investigator) or a urinary tract infection in the last 3 months