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

Eligibility 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.
• 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