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<p>Sepsis-associated acute kidney injury (S-AKI) is a severe complication characterized by high morbidity and mortality, driven by multi-organ dysfunction. Recent evidence suggests that pyroptosis, a form of programmed cell death distinct from apoptosis and necrosis, plays a critical role in the pathophysiology of S-AKI. This review examines the mechanisms of pyroptosis, focusing on inflammasome activation (e.g., NLRP3), caspase-mediated processes, and the role of Gasdermin D in renal tubular damage. We also discuss the contributions of inflammatory mediators, oxidative stress, and potential therapeutic strategies targeting pyroptosis, including inflammasome inhibitors, caspase inhibitors, and anti-inflammatory therapies. Lastly, we highlight the clinical implications and challenges in translating these findings into effective treatments, underscoring the need for personalized medicine approaches in managing S-AKI.&#xa0;</p>

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Pyroptosis in sepsis-associated acute kidney injury: mechanisms and therapeutic perspectives

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年4月23日

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  • Wenyu Wu,
  • Wanning Lan,
  • Xin Jiao,
  • Kai Wang,
  • Yawen Deng,
  • Rui Chen,
  • Ruifeng Zeng,
  • Jun Li

摘要

Sepsis-associated acute kidney injury (S-AKI) is a severe complication characterized by high morbidity and mortality, driven by multi-organ dysfunction. Recent evidence suggests that pyroptosis, a form of programmed cell death distinct from apoptosis and necrosis, plays a critical role in the pathophysiology of S-AKI. This review examines the mechanisms of pyroptosis, focusing on inflammasome activation (e.g., NLRP3), caspase-mediated processes, and the role of Gasdermin D in renal tubular damage. We also discuss the contributions of inflammatory mediators, oxidative stress, and potential therapeutic strategies targeting pyroptosis, including inflammasome inhibitors, caspase inhibitors, and anti-inflammatory therapies. Lastly, we highlight the clinical implications and challenges in translating these findings into effective treatments, underscoring the need for personalized medicine approaches in managing S-AKI.