Open AccessCell Death Pathways Drive Necroinflammation during Acute Kidney Injury
Author(s) -
Anne von Mäßenhausen,
Wulf Tonnus,
Andreas Linkermann
Publication year - 2018
Publication title -
the nephron journals/nephron journals
Language(s) - Uncategorized
Resource type - Journals
SCImago Journal Rank - 0.951
H-Index - 72
eISSN - 2235-3186
pISSN - 1660-8151
DOI - 10.1159/000490807
Subject(s) - necroptosis , medicine , acute tubular necrosis , nephron , acute kidney injury , kidney , kidney disease , necrosis , transplantation , nephrology , kidney transplantation , pathology , programmed cell death , immunology , biology , apoptosis , biochemistry
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.