Regulated cell death in AKI

Area of Science:

• Nephrology
• Cell Biology
• Pathophysiology

Background:

• Acute kidney injury (AKI) is characterized by damage to renal tubules.
• Renal tubular cell death occurs through apoptosis or regulated necrosis (RN).
• Apoptosis in AKI involves extrinsic, intrinsic, and ER stress pathways converging on mitochondria.

Purpose of the Study:

• To review the mechanisms of renal tubular cell death in AKI.
• To highlight the role of apoptosis and various forms of RN in AKI.
• To discuss the potential of combination therapy targeting multiple cell death pathways.

Main Methods:

• Literature review of preclinical models and clinical samples of AKI.
• Analysis of molecular pathways regulating tubular cell death.
• Examination of mitochondrial roles in apoptosis and RN.

Main Results:

• Tubular apoptosis is well-documented in AKI, involving intrinsic, extrinsic, and ER stress pathways.
• Recent research identified multiple RN subroutines, including necroptosis and mitochondrial permeability transition.
• Other cell death pathways like pyroptosis and ferroptosis may also contribute to AKI pathophysiology.

Conclusions:

• Understanding diverse cell death mechanisms in AKI is crucial.
• Targeting multiple cell death pathways simultaneously may offer enhanced therapeutic effects for AKI.
• Further research into these pathways could lead to novel AKI treatments.