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

Prior treatment

• immunosuppressive therapy

Other illness

• presence or history of diabetes
• hemodynamically significant valvular disease
• significant lung disease requiring home oxygen
• angina (chest pain)
• non-revascularized myocardial ischemia
• 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
• Hypersensitivity to a SGLT2i
• Pre-existing liver disease
• history of recurrent urinary tract infections (in the opinion of the investigator) or a urinary tract infection in the last 3 months

Lab values

• baseline or pre-exercise echocardiogram demonstrates a reduced ejection fraction \< 50%
• currently on sodium glucose cotransporter 2 inhibitor (SGLT2i) therapy
• ALT/AST\> 3x normal (ALT = alanine aminotransferase AST = aspartate aminotransferase)

Other

• coronary revascularization within the last 6 months
• systolic BP \<100 or \>180 mmHg
• pregnancy

• \>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 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.