LAUSR

Objective: Inhibitors of the sodium-glucose cotransporter 2 slow the progression of diabetic kidney disease, possibly by reducing the proximal tubule transport workload with subsequent improvement of renal oxygenation. We aimed to test this hypothesis in individuals with type 1 diabetes and albuminuria. Research Design and Methods: A randomized, double-blinded, crossover study with a single dose of 50 mg dapagliflozin and placebo separated by a two-week washout period. Magnetic resonance imaging (MRI) was used to assess renal tissue oxygenation (R2*), renal perfusion (arterial spin labelling) and renal artery flow (phase contrast imaging) at baseline and three and six hours from intervention. Exploratory outcomes, including baroreflex sensitivity, peripheral blood oxygen saturation and peripheral blood mononuclear mitochondrial oxygen consumption rate, were evaluated at baseline and 12 hours from intervention. Results: We included 15 individuals (33% females) with a mean (±SD) age 58±14 years, median [Q1;Q3] urinary albumin creatinine ratio of 46 [21;58] mg/g and eGFR of 73±32 ml/min/1.73m2. The mean changes (±SE) in renal cortical R2* from baseline to six hours were for dapagliflozin -1.3±0.7 s-1 and for placebo +1.4±0.7 s-1 respectively, resulting in a difference between interventions of -2.6 s-1 (95% CI, -4.5 to -0.7, p=0.001). No between-intervention differences were found in other MRI outcomes, physiological parameters or exploratory outcomes. Conclusions: Dapagliflozin improved renal cortical R2* without changing renal perfusion and blood flow. This suggests an improved renal cortical oxygenation due to reduced tubular transport work in the proximal tubules. Disclosure J. Laursen: None. P. Groop: Advisory Panel; Self; AstraZeneca, Bayer AG, Boehringer Ingelheim International GmbH, Merck Sharp & Dohme Corp., Speaker’s Bureau; Self; Boehringer Ingelheim International GmbH, Mundipharma International. M. Frimodt-moeller: None. U. B. Andersen: Other Relationship; Self; Bayer AG. P. Rossing: Advisory Panel; Self; Astellas Pharma Inc., AstraZeneca, Bayer AG, Boehringer Ingelheim International GmbH, Gilead Sciences, Inc., Merck KGaA, Merck Sharp & Dohme Corp., Novo Nordisk A/S, Sanofi, Vifor Pharma Management Ltd. N. S. Heinrich: Stock/Shareholder; Self; Akebia Therapeutics, Inc., Novo Nordisk A/S. J. Melo: None. B. Haddock: None. I. B. Rasmussen: None. F. Safavimanesh: None. C. S. Hansen: None. J. Storling: None. H. B. W. Larsson: None.