- Change in 24-hr proteinuria with dapagliflozin for six weeks relative to placebo in patients with non-diabetic kidney disease and proteinuria 500 mg/day on stable angiotensin-converting enzyme inhibitor or angiotensin II receptor blocker treatment. [ Time Frame: 6 weeks ]
- Effect of dapagliflozin 10 mg/d compared to placebo on Glomerular Filtration Rate (GFR) using iohexol clearance [ Time Frame: 6 weeks ]
- Effect of dapagliflozin 10 mg/d compared to placebo on systolic/diastolic blood pressure [ Time Frame: week 0, 2, 4, 5, 6, 12, 15, 18, 24 ]
- Effect of dapagliflozin 10 mg/d compared to placebo on body weight [ Time Frame: week 0, 2, 4, 5, 6, 12, 15, 18, 24 ]
- Effect of dapagliflozin 10 mg/d compared to placebo on selected neurohormones/ biomarkers [ Time Frame: week 0, 3, 6, 12, 15, 18, 24 ]
- Safety of dapagliflozin vs. placebo – the number of hypoglycemia episodes between groups and serious adverse events [ Time Frame: week 0-26 ]
Despite optimal treatment with renin-angiotensin-aldosterone-system (RAAS) inhibitors, many patients with non-diabetic kidney disease show progressive kidney function loss, which is associated with high residual proteinuria. Novel treatment strategies are therefore required to further decrease proteinuria and to slow kidney function decline.
Dapagliflozin is a sodium-glucose transport (SGLT2) inhibitor and inhibits the reabsorption of glucose and sodium in the proximal tubule. The increased natriuresis following dapagliflozin administration normalizes tubuloglomerular feedback resulting in a reduction in intra-glomerular hypertension, which is in turn manifested by acute reversible reductions in glomerular filtration rate and albuminuria. Since many etiologies of non-diabetic nephropathy are characterized by intraglomerular hypertension, we hypothesize that dapagliflozin acutely decreases GFR and proteinuria in patients without diabetes at risk of progressive kidney function loss via a glucose independent hemodynamic mechanism.