Cell Death Pathways Drive Necroinflammation during Acute Kidney Injury.
Renal tubules represent an intercellular unit and function as a syncytium. When acute tubular necrosis was first visualized to occur through a process of synchronized regulated necrosis (SRN) in handpicked primary renal tubules, it became obvious that SRN actually promotes nephron loss. This realization adds to our current understanding of acute kidney injury (AKI)-chronic kidney disease (CKD) transition and argues for the prevention of AKI episodes to prevent CKD progression. Because SRN is triggered by necroptosis and executed by ferroptosis, 2 recently identified signaling pathways of regulated necrosis, a combination therapy employing necrostatins and ferrostatins may be beneficial for protection against nephron loss. Clinical trials in AKI and during the process of kidney transplantation are now required to prevent SRN. Additionally, necrotic cell death drives autoimmunity and necroinflammation and therefore represents a therapeutic target even for the prevention of antibody-mediated rejection of allografts years after the transplantation process.
['von Mässenhausen|Anne|A|', 'Tonnus|Wulf|W|', 'Linkermann|Andreas|A|']
D058186:Acute Kidney Injury D017209:Apoptosis D016923:Cell Death D018450:Disease Progression D006801:Humans D007668:Kidney D009336:Necrosis D009393:Nephritis
Necroinflammation Necroptosis Ferroptosis Receptor-interacting protein kinase 3 Acute kidney injury-chronic kidney disease transition Apoptosis Gasdermin Mixed lineage kinase domain-like Pyroptosis