Mechanisms and Therapeutics in Acute Kidney Injury

Acute kidney injury (AKI) is characterised by a rapid decline in renal function resulting from diverse insults such as ischaemia–reperfusion, nephrotoxicity, sepsis and rhabdomyolysis. Central to its pathogenesis are haemodynamic alterations, tubular epithelial cell injury, inflammation and oxidative stress, culminating in cell death by apoptosis or necrosis. Key molecular pathways include activation of reactive oxygen species, pro-inflammatory cytokines and complement components, as well as stress-responsive transcription factors. Conventional management remains largely supportive, focusing on fluid and electrolyte balance, avoidance of further renal insults and renal replacement therapy when indicated. However, growing insight into redox biology, innate immunity and regenerative medicine has fostered novel approaches. These include pharmacological modulation of antioxidant-responsive elements, inhibition of pro-apoptotic kinases, targeted anti-inflammatory agents and cell-based therapies. Progress in identifying reliable biomarkers has also facilitated earlier diagnosis and risk stratification. Understanding the interplay between these mechanisms is vital to translate preclinical advances into effective therapies that reduce AKI incidence, accelerate recovery and mitigate progression to chronic kidney disease.

Research from Nature Portfolio

Recent studies have elucidated the renoprotective actions of natural and cell-based therapies. One investigation demonstrated that curcumin administration in experimental rhabdomyolysis-induced AKI attenuates tubular injury by activating the AMPK and Nrf2/HO-1 antioxidant pathways while engaging the PI3K/Akt survival cascade. This dual modulation reduced lipid peroxidation, suppressed pro-inflammatory cytokines and limited apoptosis. In parallel, tissue-engineered delivery of mesenchymal stem cells (MSCs) via a biological membrane scaffold has been shown to preserve renal architecture and function in glycerol-induced injury. The MSCs secreted paracrine factors that activated PI3K/Akt signalling in tubular cells, inhibited caspase-mediated apoptosis and promoted tubular regeneration. Together, these findings highlight convergent mechanisms—antioxidant defence enhancement and anti-apoptotic signal activation—that may be harnessed to develop adjunctive therapies for AKI.

Mechanisms and Therapeutics in Acute Kidney Injury publication trend

The graph below shows the total number of articles in mechanisms and therapeutics in acute kidney injury across all publications each year (not limited to Nature Index journals).

Technical terms

Ischaemia–reperfusion injury: Tissue damage resulting from transient loss of blood flow followed by restoration, leading to oxidative stress and inflammation.

Oxidative stress: Imbalance between reactive oxygen species production and antioxidant defences, causing cellular damage.

Nrf2/HO-1 pathway: A cytoprotective axis in which Nrf2 induces heme oxygenase-1 to counteract oxidative injury.

PI3K/Akt pathway: A cell survival signalling cascade that inhibits apoptosis and promotes cell growth.

Mesenchymal stem cells (MSCs): Multipotent stromal cells capable of secreting regenerative and immunomodulatory factors.

Hyperbaric oxygenation: A therapy involving inhalation of 100% oxygen at elevated atmospheric pressure to enhance tissue oxygenation and antioxidant defences.

References

1. Effect of curcumin on glycerol-induced acute kidney injury in rats. Scientific Reports (2017).
2. Biological Membrane-Packed Mesenchymal Stem Cells Treat Acute Kidney Disease by Ameliorating Mitochondrial-Related Apoptosis. Scientific Reports (2017).
3. Selenoprotein GPX3 regulates NADPH oxidase expression by inhibiting the MAPK signaling pathway and thereby attenuating the inflammatory response in renal ischemia-reperfusion injury. Genes & Diseases (2025).
4. Hyperbaric Oxygenation: Can It Be a Novel Supportive Method in Acute Kidney Injury? Data Obtained from Experimental Studies. Cells (2024).