LAUSR

Childhood/prepubertal obesity (PPO) is a world-wide epidemic and is considered a risk factor for renal injury. Therefore, there is a need to control this trend to decrease the future risk of chronic kidney disease. Recently, we reported that the SSLepRmutant rat is a novel model to study the mechanisms of renal injury associated with PPO. The SSLepRmutant rat develops progressive renal injury in the absence of hyperglycemia before puberty. SGLT2 inhibitors have been demonstrated to exert renoprotective effects independent of lowering blood glucose. Therefore, the objective of this study was to determine the effects of SGLT2 blockade with empagliflozin on the early progression of proteinuria in SSLepRmutant rats, during PPO. Four-week-old SS and SSLepRmutant rats (n = 5/group) were either treated with vehicle (diet) or empagliflozin (30 mg/kg/day, orally) for four weeks. While the SSLepRmutant rats had significantly higher body weights vs SS rats, there were no detectable differences in body weight or blood glucose levels in response to empagliflozin treatment in SSLepRmutant rats. We observed a significant increase in plasma insulin in control SSLepRmutant rats vs SS rats (7±1 vs 1±0.3 ng/mL, respectively, p<0.05), and treatment with empagliflozin did not have any effect on plasma insulin in SSLepRmutant rats (8±2 ng/mL). At baseline, we did not observe any significant difference in urine flow rate between control SSLepRmutant vs SS rats. After two weeks of treatment, while there was no observed difference in urine flow rate between SSLepRmutant and SS rats (17±3 ml/day vs 18±2 ml/day, respectively), empagliflozin significantly increased urine flow rate in SSLepRmutant rats (29±4 ml/day, p<0.05), but not in SS rats (17±3 ml/day). At baseline, we observed a difference in proteinuria between control SSLepRmutant vs SS rats (68±11 vs 6±3 mg/day, respectively, p<0.05), which remained elevated over the course of the study (471±75 vs 32±5 mg/day, respectively, p<0.05). Treatment with empagliflozin significantly decreased proteinuria in SSLepRmutant rats (223±52 mg/day, p<0.05) without affecting SS rats (27±8 mg/day). At the end of the study, we observed a significant increase in GFR in control SSLepRmutant rats vs SS rats (2.4±0.6 vs 0.5 mL/min/gkwt, respectively, p<0.05). Treatment with empagliflozin only significantly reduced GFR in SSLepRmutant rats (0.9±0.2 mL/min/gkwt, p<0.05). In conclusion, these data suggest that empagliflozin attenuates renal hyperfiltration and confers renoprotective effects during the early progression of renal disease associated with PPO. DK109133 and HL151407 This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.