Mechanisms and therapeutic potential of multiple forms of programmed cell death in renal fibrosis

Programmed cell death (PCD), particularly necroptosis, ferroptosis, and pyroptosis alongside classical apoptosis has attracted considerable attention in recent years in the context of renal fibrosis (RF). Accumulating evidence indicates that these regulated cell death pathways contribute substantially to renal tissue damage and fibrosis progression by promoting inflammation and extracellular matrix (ECM) accumulation. Renal fibrosis, a common pathological process to various chronic kidney diseases (CKD), is closely intertwined with diverse forms of cell death. Elucidating the underlying molecular mechanisms is critical for identifying effective therapeutic targets. This review systematically summarizes the signaling mechanisms of apoptosis, necroptosis, ferroptosis, and pyroptosis, detailing their roles in the pathogenesis of RF. We analyze recent advances in pharmacological treatment and emerging therapies targeting these pathways, and explore potential therapeutic targets for clinical implementation. Targeting multiple forms of regulated cell death pathways concurrently may offer a promising avenue for the precision treatment of RF.