Ischemia-Reperfusion Injury Mechanisms in Renal Systems

Ischaemia-reperfusion injury (IRI) in renal systems arises when blood supply to the kidney is interrupted and then restored, triggering a cascade of molecular and cellular events that can culminate in acute kidney injury (AKI), delayed graft function following transplantation and progression to chronic kidney disease (CKD). During the ischaemic phase, hypoxia leads to ATP depletion, disruption of ionic gradients and mitochondrial dysfunction. Upon reperfusion, sudden reoxygenation fuels the generation of reactive oxygen species (ROS), overwhelming endogenous antioxidant defences and promoting lipid peroxidation, protein oxidation and DNA damage. In parallel, damaged tubular epithelial cells release damage-associated molecular patterns that activate resident immune cells and recruit circulating leukocytes, fuelling inflammation and microvascular dysfunction. Endothelial injury, cell death programmes such as apoptosis and pyroptosis, and activation of the coagulation cascade exacerbate tissue injury. Over weeks to months, maladaptive repair pathways involving fibroblast activation and extracellular matrix deposition drive interstitial fibrosis and nephron loss, underpinning progression to CKD. Recent advances have elucidated key mediators in this process, including metabolic reprogramming, immune-metabolic crosstalk and novel cell death modulators. Understanding these interwoven mechanisms is critical to developing targeted therapies to mitigate IRI and improve global outcomes in renal transplantation and critical care.

Research from Nature Portfolio

No recent Nature Portfolio content available.

Ischemia-Reperfusion Injury Mechanisms in Renal Systems publication trend

The graph below shows the total number of articles in ischemia-reperfusion injury mechanisms in renal systems across all publications each year (not limited to Nature Index journals).

Technical terms

Ischaemia: Interruption of blood supply leading to tissue hypoxia and metabolic stress.
Reperfusion: Restoration of blood flow that paradoxically exacerbates injury through ROS generation.
Reactive oxygen species (ROS): Highly reactive molecules that damage lipids, proteins and DNA when uncontrolled.
Pyroptosis: Proinflammatory form of programmed cell death mediated by gasdermin activation.
Fibronectin: Extracellular matrix glycoprotein involved in cell adhesion, migration and wound healing.

References

1. Dimethyl malonate preserves renal and mitochondrial functions following ischemia-reperfusion via inhibition of succinate dehydrogenase. Redox Biology (2023).
2. Epithelial CEBPD activates fibronectin and enhances macrophage adhesion in renal ischemia-reperfusion injury. Cell Death Discovery (2024).
3. The Role of Oxidative Stress in Kidney Injury. Antioxidants (2023).