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Abstract: PO0374

Head-to-Head Comparison of Two SGLT-2 Inhibitors on AKI Outcomes in a Rat Ischemia-Reperfusion Model

Session Information

Category: Acute Kidney Injury

  • 103 AKI: Mechanisms

Authors

  • Chu, Chang, Universitatsklinikum Mannheim, Mannheim, Baden-Württemberg, Germany
  • Delic, Denis, Boehringer Ingelheim International GmbH, Biberach, Rheinland-Pfalz, Germany
  • Xiong, Yingquan, Charite Universitatsmedizin Berlin, Berlin, Berlin, Germany
  • Luo, Ting, Jinan University First Affiliated Hospital, Guangzhou, Guangdong, China
  • Hasan, Ahmed A., Universitatsklinikum Mannheim, Mannheim, Baden-Württemberg, Germany
  • Zeng, Shufei, Universitatsklinikum Mannheim, Mannheim, Baden-Württemberg, Germany
  • Gaballa, Mohamed Mahmoud Salem Ahmed, Universitatsklinikum Mannheim, Mannheim, Baden-Württemberg, Germany
  • Chen, Xin, Charite Universitatsmedizin Berlin, Berlin, Berlin, Germany
  • Klein, Thomas, Boehringer Ingelheim International GmbH, Biberach, Rheinland-Pfalz, Germany
  • Elitok, Saban, Klinikum Ernst von Bergmann gGmbH, Potsdam, Brandenburg, Germany
  • Krämer, Bernhard K., Universitatsklinikum Mannheim, Mannheim, Baden-Württemberg, Germany
  • Hocher, Berthold, Universitatsklinikum Mannheim, Mannheim, Baden-Württemberg, Germany
Background

The CREDENCE trial testing canagliflozin and the EMPA-REG OUTCOME trial testing empagliflozin suggest different effects on acute kidney injury (AKI). Since the diagnosis of AKI was made in these studies usually based on changes of serum creatinine (sCr) although changes of sCr may reflect the mode of action of SGLT-2 inhibitors.

Methods

We analyzed both drugs in a rat AKI model (ischemia-reperfusion injury (IRI) model) focusing on established morphological and biochemical AKI markers. Four groups were analyzed: sham, IRI+placebo, IRI+canagliflozin, IRI+empagliflozin.

Results

Urinary glucose excretion was comparable in both treatment groups indicating comparable SGLT-2 inhibition. Comparing GFR surrogate markers after IRI (sCr and BUN). At all investigated time points after IRI, sCr and BUN were higher in the IRI+canagliflozin group than placebo-treated rats, whereas the empagliflozin group did not differ from the placebo group. IRI led to tubular dilatation and necrosis. Empagliflozin was able to reduce that finding whereas canagliflozin had no effect. Renal expression of KIM-1 increased after IRI and empagliflozin but not canagliflozin normalized KIM-1 expression (Figure). IRI reduced urinary microRNA-26a excretion. Empagliflozin but not canagliflozin was able to restore normal levels of urinary miR-26a.

Conclusion

In conclusion, our study confirmed the observations made in the CREDENCE and the EMPA-REG OUTCOME trials. The empagliflozin effects on KIM-1 and miR-26a might indicate beneficial regulation of inflammation and innate immune response. Our data should stimulate clinical studies analyzing whether empagliflozin is a preferable SGLT-2 inhibitor in patients at high AKI risk.