Pyroptosis and sepsis-associated acute kidney injury.

Abstract

Pyroptosis is a form of programmed cell death triggered by inflammatory caspases, dependent on the gasdermin (GSDM) family proteins forming membrane pores in the plasma membrane, with GSDM proteins serving as the executors of pyroptosis. This process can activate a robust inflammatory response through a cascade effect. Sepsis-associated acute kidney injury (SA-AKI) is a classical inflammatory disease with no specific therapeutic drug available. Studies have highlighted the role of pyroptosis in the onset and progression of SA-AKI, yet the specific renal cell populations affected by pyroptosis and the detailed regulatory mechanisms remain unclear. Pyroptosis may be closely related to SA-AKI, with current strategies for regulating pyroptosis focusing on targeting inflammasomes, key caspase enzymes, GSDM proteins, and downstream inflammatory factors. Although these strategies still present some off-target effects or side effects, they provide a foundation for research into sepsis-targeted therapies and clarify future research directions and the necessity of such studies.