869-P: Effect of Dapagliflozin on Renal Oxygen Delivery and Consumption in T2DM and NGT Subjects

Abstract

Improved renal oxygenation is proposed as a potential reno-protective mechanism of SGLT2 inhibitors in T2DM. Bold-MRI studies in nondiabetic subjects showed no effect with dapagliflozin and improved renal cortical oxygenation with empagliflozin in T1DM. No studies have examined renal oxygenation in T2DM. We examined the effect of dapagliflozin (10 mg) on renal oxygen delivery and oxygen consumption in 7 T2DM (age=58±3 yrs, BMI = 30±1.8 kg/m2) and 7 NGT (age = 47±3.4 yrs, BMI = 28.6±1.6kg/m2) subjects who received a single dose of dapagliflozin or placebo. Renal vein (SvO2) and radial artery (SaO2) hemoglobin saturation were measured with i-STAT point of care analyzer and renal blood flow with PAH infusion before and 4 hours after dapagliflozin/placebo. At baseline arterial (CaO2, 19 ± 0.8 vs 19 ± 0.7 ml/dl, p=NS) and renal venous (CvO2, 16 ± 0.9 vs 18 ± 0.7 ml/dl, p=NS) oxygen Content were similar in DAPA and PLAC. Thus, there was no difference in renal oxygen delivery (478 ± 29 vs 533 ±27 ml/min/m2) between DAPA and PLAC groups. Following DAPA/PLAC renal plasma flow did not change, and there was no change in arterial (CaO2) (19 ± 0.8 vs 18.2 ± 0.7 ml/dl, p=NS) or renal venous (CvO2) (16 ± 0.9 vs 15.5 ± 0.9 ml/dl) oxygen content in DAPA or PLAC groups. Renal oxygen consumption following DAPA (67 ± 10 vs 78 ±13 ml/min/m2, p=NS) and PLAC (42 ± 8 vs 50 ± 6 ml/min/m2, p=NS) groups were not different versus baseline. Conclusion: A single acute dose of dapagliflozin does not alter renal oxygen delivery or consumption in T2DM or NGT subjects. Disclosure D. Tripathy: None. X. Chen: None. R. Chilton: None. A.A. Hansis-Diarte: None. M. Salehi: None. C. Solis-Herrera: None. E. Cersosimo: None. R.A. DeFronzo: Speaker's Bureau; AstraZeneca. Advisory Panel; AstraZeneca, Bayer Inc., Boehringer-Ingelheim, Novo Nordisk. Research Support; AstraZeneca, Boehringer-Ingelheim, Merck & Co., Inc. Funding AstraZeneca