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

The goal of this study is to better understand the effects of a sodium-glucose transport protein 2 inhibitor, dapagliflozin, added on to standard of care on heart and lung function and circulating metabolites (substances created when our bodies break down food, drugs, or its own tissues) in patients with chronic kidney disease.

Inclusion Criteria:>18 years of ageeGFR 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 blockerEvidence 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 diabetescoronary revascularization within the last 6 monthshemodynamically significant valvular diseasesignificant lung disease requiring home oxygenangina (chest pain)non-revascularized myocardial ischemiasystolic BP <100 or >180 mmHgpregnancyclinical heart failure symptomshistory of systemic disease processes that can cause HFpEF such as amyloidosis or sarcoidosisany musculoskeletal or chronic condition that will interfere with completion of cardiac testingactive cancerimmunosuppressive therapybaseline or pre-exercise echocardiogram demonstrates a reduced ejection fraction </= 50%currently on sodium glucose cotransporter 2 inhibitor (SGLT2i) therapyHypersensitivity to a SGLT2iPre-existing liver diseaseALT/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