#2792 Dapagliflozin's effect on kidney oxygenation: analysis of functional MRI data from the randomized GLUTREPRO trial

Abstract Background and Aims Renal hypoxia is believed to play a central role in the pathophysiology of both diabetic and non-diabetic chronic kidney disease (CKD). Dapagliflozin has been shown to slow the progression of kidney disease by counteracting several pathogenic mechanisms. The advent of blood oxygenation level-dependent magnetic resonance imaging (BOLD-MRI) has enabled the noninvasive assessment of renal oxygenation in humans. However, it remains uncertain whether dapagliflozin affects changes renal oxygenation as measured by BOLD-MRI. The aim of the study was to assess whether dapagliflozin modifies kidney oxygenation as a possible mechanism of kidney protection. Method The GLUTREPRO study was a randomized controlled trial investigating the effect of dapagliflozin on kidney measures. A secondary end-point of the study was to investigate the changes in global and segmental renal oxygenation estimated by BOLD MRI (changes in R2* value defined as 1/T2*) after randomization to dapagliflozin or placebo. We analyzed data of 360 ROI from 20 patients who underwent BOLD-MRI at baseline and at month 3 after randomization on a 3 Tesla MR scanner. Results In BOLD-MRI, the medullary transverse relaxation rate R2* decreased (indicating increased tissue oxygenation) in the dapagliflozin-treated group, while it tended to increase in the placebo group. Accordingly, medullary R2* values at month 3 were significantly lower in the treated group compared to the placebo group (Fig. 1, P = 0.0149). In contrast, cortical kidney oxygenation was not affected by the administration of dapagliflozin. The effect of dapagliflozin on medullary oxygenation changes appears to be more pronounced in non-diabetic patients (Table 1). Considering all available R2* measurements and dividing the R2* variation into tertiles, we investigated the clinical and laboratory parameters significantly associated with changes in renal medullary oxygenation. The inverse relationship we observed between changes in R2* and changes in eGFR and ACR in the placebo group, was attenuated in patients treated with dapagliflozin. Notably, dapagliflozin was identified as the sole independent determinant of improved medullary renal oxygenation (β −14.4, 95% CI −23.9 / β −4.89, P = 0.003, Table 2). Conclusion This prospective sub-study of the GLUTREPRO trial revealed a potentially protective effect of dapagliflozin on renal medullary oxygenation.