Background

Sepsis-induced systemic inflammation response syndrome is the leading cause of morbidity and mortality among patients in intensive care units in North America. While sepsis is associated with multiple organ damage, acute renal injury represents a hallmark of sepsis. Since systemic and renal inflammation is known to play a vital role in morbidity and mortality associated with sepsis, identifying a potent anti-inflammatory agent may help minimize morbidity and mortality associated with acute septic kidney injury. Since recent work has suggested that empagliflozin, a renal sodium-glucose cotransporter 2 (SGLT2) inhibitor, may assist in the treatment of inflammatory diseases, our objective was to examine the effect of empagliflozin on acute sepsis-induced renal injury.

Method

Mice were treated with three daily doses of empagliflozin or vehicle, with lipopolysaccharide (LPS) administered on the third day, at the same time as the third dose of empagliflozin or vehicle. In another cohort, mice were injected with a single dose of LPS 3 h before a dose of empagliflozin.

Results

Our results show that empagliflozin improves survival in a mouse model of LPS-induced septic shock. We further demonstrate that the beneficial effects of empagliflozin are likely mediated via reducing LPS-induced acute renal injury. Moreover, our data indicate that empagliflozin significantly reduces systemic and renal inflammation to contribute to the improvements observed in an LPS-model of acute septic renal injury.

Conclusion

Overall, the findings of this study suggest that empagliflozin could be repurposed to reduce morbidity and mortality in patients with acute septic renal injury.

Trial registration

Not applicable.

中文翻译：

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Empagliflozin 抑制炎症并防止急性败血性肾损伤。

背景

脓毒症引起的全身炎症反应综合征是北美重症监护病房患者发病率和死亡率的主要原因。虽然败血症与多器官损伤有关，但急性肾损伤是败血症的标志。由于已知全身性和肾脏炎症在与脓毒症相关的发病率和死亡率中起着至关重要的作用，因此确定一种有效的抗炎剂可能有助于最大限度地减少与急性脓毒症肾损伤相关的发病率和死亡率。由于最近的工作表明恩格列净（一种肾钠-葡萄糖协同转运蛋白 2 (SGLT2) 抑制剂）可能有助于治疗炎症性疾病，因此我们的目标是检查恩格列净对急性败血症引起的肾损伤的影响。

方法

小鼠每天服用三剂恩格列净或赋形剂，第三天给予脂多糖 (LPS)，与第三剂恩格列净或赋形剂同时给药。在另一个队列中，小鼠在注射恩格列净前 3 小时注射了单剂 LPS。

结果

我们的结果表明，empagliflozin 可提高 LPS 诱导的感染性休克小鼠模型的存活率。我们进一步证明，恩格列净的有益作用可能是通过减少 LPS 诱导的急性肾损伤来介导的。此外，我们的数据表明，恩格列净显着减少全身和肾脏炎症，有助于在急性败血性肾损伤 LPS 模型中观察到的改善。

结论

总的来说，这项研究的结果表明，恩格列净可以重新用于降低急性败血性肾损伤患者的发病率和死亡率。

试用注册

不适用。