Targeting of regulated necrosis in kidney disease

Area of Science:

• Nephrology
• Cell Biology
• Immunology

Background:

• Acute tubular necrosis (ATN) was historically viewed as unregulated cell death, limiting therapeutic options.
• Recent research redefines cell death in acute kidney injury (AKI), moving beyond simple necrosis.
• Apoptosis and regulated necrosis pathways have distinct roles and therapeutic implications in AKI.

Purpose of the Study:

• To review the emerging concept of regulated necrosis in acute kidney injury.
• To explore various modalities of regulated necrosis, including necroptosis, ferroptosis, and pyroptosis.
• To discuss the therapeutic potential and immunogenic consequences of regulated necrosis in AKI and kidney transplantation.

Main Methods:

• Literature review of recent advances in cell death research in AKI.
• Analysis of morphological and molecular mechanisms of apoptosis versus regulated necrosis.
• Examination of evidence linking regulated necrosis to kidney injury and transplantation outcomes.

Main Results:

• Regulated necrosis, unlike apoptosis, can be pro-inflammatory and immunogenic, posing challenges for kidney transplantation.
• Specific molecular pathways (e.g., necroptosis, ferroptosis) represent novel therapeutic targets.
• Synchronized necrosis, where entire tubules undergo cell death, is a newly described phenomenon.

Conclusions:

• The understanding of cell death in AKI has evolved significantly, challenging the traditional view of ATN.
• Regulated necrosis pathways offer promising avenues for therapeutic intervention in AKI.
• Targeting regulated necrosis may improve outcomes in kidney injury and transplantation by modulating inflammation and immunogenicity.