Pyroptosis-induced tissue damage in kidney disease

Pyroptosis is a form of programmed cell death that differs mechanistically from apoptosis and is characterized by a robust inflammatory response. It is primarily mediated by proteins of the gasdermin family, which form pores in the cell membrane, leading to osmotic cell lysis and the release of pro-inflammatory cytokines. As a process triggered by various pathological stimuli like infection, inflammation, and oxidative stress, pyroptosis contributes to a range of diseases, including autoimmune disorders and cancer. Evidence indicates that pyroptosis, a crucial innate immune component, promotes host defense by facilitating immune cell recruitment and tissue repair. However, dysregulated pyroptosis is a key driver of pathology, contributing to chronic inflammation, fibrosis, and tissue damage in a range of conditions such as kidney, cardiovascular, and metabolic disorders. More evidence suggests that pyroptosis may dominate the process of irreversible damage to renal tissue and may accelerate the time for patients to enter end-stage renal disease. At present, when diagnosing kidney diseases and performing kidney biopsy, more attention is paid to the extent of kidney tissue damage, which is strongly related to the prognosis of patients. Given that many kidney diseases, especially acute kidney injury, involve inflammatory responses, targeting dysregulated pyroptosis presents a potential strategy for alleviating irreversible renal damage. This review will provide a detailed description of the signaling pathways of pyroptosis, with a focus on the mechanisms of pyroptosis-induced renal tissue damage and new advances in treatment.