Renal Ischemia-Reperfusion Injury and Oxidative Stress

Renal ischemia-reperfusion injury (IRI) arises when blood supply to the kidney is interrupted and then restored, triggering a cascade of cellular and molecular events that culminate in tubular epithelial damage, inflammation and vascular dysfunction. The initial ischemic phase induces hypoxia, ATP depletion and loss of ionic homeostasis, compromising tubular cell integrity. Upon reperfusion, the abrupt reintroduction of oxygen fuels a burst of reactive oxygen species (ROS), overwhelming endogenous antioxidant defences. Excess ROS provoke lipid peroxidation, protein oxidation and DNA damage, thereby amplifying inflammation through activation of innate immune receptors and pro-inflammatory cytokine release. Mitochondrial dysfunction lies at the heart of this process, as impaired oxidative phosphorylation and disturbed mitochondrial dynamics both fuel ROS production and compromise energy supply. Endothelial injury and microvascular congestion further exacerbate tissue hypoxia, creating a vicious circle of oxidative stress and cell death by apoptosis or necrosis. Globally, IRI is a leading cause of acute kidney injury in settings such as transplantation, major surgery and shock, and it predisposes to chronic kidney disease through maladaptive repair and interstitial fibrosis. Advances in understanding redox signalling, mitochondrial quality control, cellular senescence and immunometabolism offer new avenues for therapeutic intervention, from antioxidant strategies and mitochondrial stabilisers to targeted modulation of inflammatory pathways.

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Renal Ischemia-Reperfusion Injury and Oxidative Stress publication trend

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

Technical terms

Ischemia-reperfusion injury: Tissue damage caused by the restoration of blood flow after a period of oxygen deprivation.

Oxidative stress: An imbalance between the production of reactive oxygen species and the capacity of antioxidant defences.

Reactive oxygen species (ROS): Highly reactive molecules derived from oxygen that can damage cellular components.

Renal tubular epithelial cells: Kidney cells lining the tubules that are crucial for reabsorption and susceptible to hypoxic and oxidative injury.

Mitochondrial dysfunction: Impaired mitochondrial activity leading to reduced ATP generation and increased ROS production.

References

1. Knockout of Toll-Like Receptors 2 and 4 Prevents Renal Ischemia-Reperfusion-Induced Cardiac Hypertrophy in Mice. PLOS ONE (2015).
2. FFAR4 improves the senescence of tubular epithelial cells by AMPK/SirT3 signaling in acute kidney injury. Signal Transduction and Targeted Therapy (2022).
3. Stanniocalcin-1 Protects a Mouse Model from Renal Ischemia-Reperfusion Injury by Affecting ROS-Mediated Multiple Signaling Pathways. International Journal of Molecular Sciences (2016).