Summary
Necrosis is the predominant form of regulated cell death in acute kidney injury (AKI)
and represents results in the formation of casts that appear in the urine sedimentation,
referred to as muddy brown casts, which are part of the diagnosis of AKI. Pathologists referred to this typical feature
as acute tubular necrosis. We are only beginning to understand the dynamics and the
molecular pathways that underlie such typical necrotic morphology. In this review,
we provide an overview of candidate pathways and summarize the emerging evidence for
the relative contribution of these pathways of regulated necrosis, such as necroptosis,
ferroptosis, mitochondrial permeability transition–mediated regulated necrosis, parthanatos,
and pyroptosis. Inhibitors of each of these pathways are available, and clinical trials
may be started after the detection of the most promising drug targets, which will
be discussed here. With the global burden of AKI in mind, inhibitiors of regulated
necrosis represent promising means to prevent this disease.
Keywords
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Article info
Footnotes
☆☆Financial support: This study was supported by grants from The Netherlands Organization for Scientific Research (91712386 to J.C.L.), the European Renal Association - European Dialysis and Transplant Association (ERA-EDTA) (ALTF 69-2010 to J.K.), and funding from the German Research foundation, Cluster of Excellence Inflammation at Interfaces (EXC306 to A.L.).
☆Conflicts of interest statement: none.
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