Role of necroptosis in kidney health and disease

Cell death, particularly that of tubule epithelial cells, contributes critically to the pathophysiology of kidney disease. A body of evidence accumulated over the past 15 years has ascribed a central pathophysiological role to a particular form of regulated necrosis, termed necroptosis, to acute tubular necrosis, nephron loss and maladaptive renal fibrogenesis. Unlike apoptosis, which is a non-immunogenic process, necroptosis results in the release of cellular contents and cytokines, which triggers an inflammatory response in neighbouring tissue. This necroinflammatory environment can lead to severe organ dysfunction and cause lasting tissue injury in the kidney. Despite evidence of a link between necroptosis and various kidney diseases, there are no available therapeutic options to target this process. Greater understanding of the molecular mechanisms, triggers and regulators of necroptosis in acute and chronic kidney diseases may identify shortcomings in current approaches to therapeutically target necroptosis regulators and lead to the development of innovative therapeutic approaches.

Automated summary

Cell death, particularly tubule epithelial cell death, plays a critical role in the pathophysiology of kidney disease. Accumulated evidence has shown that necroptosis, a form of regulated necrosis, is involved in acute tubular necrosis, nephron loss, and renal fibrogenesis. Unlike apoptosis, necroptosis triggers an inflammatory response due to the release of cellular contents and cytokines. Despite the link between necroptosis and kidney diseases, therapeutic options targeting this process are currently unavailable. Further understanding of the molecular mechanisms and regulators of necroptosis may lead to innovative therapeutic approaches.