| Outcome Measures: |
Primary: Proximal sodium reabsorption (FENa), The difference in proximal sodium reabsorption FENa (measured using FELi) with ertugliflozin vs. placebo, Outcome will be measured at 2 time points: acute (1 week) and chronic (12 weeks) | Secondary: Glomerular Filtration Rate (GFR), The difference in GFR with ertugliflozin vs. placebo, Glomerular Filtration Rate (GFR, based on plasma inulin clearance) will be measured at 2 time points: acute (1 week) and chronic (12 weeks)|Effective Renal Plasma Flow (ERPF), The difference in ERPF with ertugliflozin vs. placebo, Effective Renal Plasma Flow (ERPF, based on paraaminohippurate plasma clearance) will be measured at 2 time points: acute (1 week) and chronic (12 weeks)|Systolic blood pressure (SBP), The difference in SBP with ertugliflozin vs. placebo, 2 time points: acute (1 week) and chronic (12 weeks)|Diastolic blood pressure (DBP), The difference in DBP with ertugliflozin vs. placebo, 2 time points: acute (1 week) and chronic (12 weeks)|Heart rate (HR), The difference in HR with ertugliflozin vs. placebo, 2 time points: acute (1 week) and chronic (12 weeks)|Echocardiography for markers of systolic and diastolic function, cardiac output, 2 time points: acute (1 week) and chronic (12 weeks)|Arterial stiffness, 2 time points: acute (1 week) and chronic (12 weeks)|Plasma volume, Plasma volume will be measured using a non-radioactive technique (indocyanine green dilution), 2 time points: acute (1 week) and chronic (12 weeks)|Extracellular water, Extracellular water will be measured non-invasively using bioimpedence spectroscopy, 2 time points: acute (1 week) and chronic (12 weeks)|Cardiac output, Cardiac output will also be measured using non-invasive cardiac monitoring (NICOM), 2 time points: acute (1 week) and chronic (12 weeks)|Systemic vascular resistance, Systemic vascular resistance will also be measured using non-invasive cardiac monitoring (NICOM), 2 time points: acute (1 week) and chronic (12 weeks)|RAAS hormones, Neurohormones/biomarkers, 2 time points: acute (1 week) and chronic (12 weeks)|Natriuretic peptides, Neurohormones/biomarkers, 2 time points: acute (1 week) and chronic (12 weeks)|Sympathetic nervous system markers, Neurohormones/biomarkers, 2 time points: acute (1 week) and chronic (12 weeks)|Urinary adenosine, Neurohormones/biomarkers, 2 time points: acute (1 week) and chronic (12 weeks)
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| Locations: |
Toronto General Hospital, Toronto, Ontario, M5G2N2, Canada|Vanderbilt University Medical Centre, Amsterdam, De Boelelaan, 1117, Netherlands|University Medical Center Groningen, Groningen, Netherlands
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