Pyroptosis in sepsis-associated acute kidney injury: mechanisms and therapeutic perspectives
Wenyu Wu, Wanning Lan, Xin Jiao, Kai Wang, Yawen Deng, Rui Chen, Ruifeng Zeng, Jun Li
Abstract
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.