Pathogenesis of intrinsic acute kidney injury

This review focuses on the pathogenesis of intrinsic acute kidney injury (AKI), emphasizing recent advances that hold therapeutic promise.

Enhanced endothelin and reduced endothelium-derived nitric oxide release in AKI can be blocked using endothelin receptor antagonists or nitric oxide supplementation. Vasodilatory agents such as theophylline and caffeine may prevent AKI. Free labile iron is a potent factor in the generation of reactive oxygen species and tubule damage in AKI. Apoptosis via induction of p53 is an important mechanism of cell death in AKI, which can be blocked using small interfering RNA. The AKI-driven reduction in nicotinamide adenine dinucleotide can be countered using oral supplements. Surviving tubule cells regenerate after AKI, by upregulating genes encoding growth factors, such as hepatocyte growth factor. Pro-angiogenic agents (statins and erythropoietin) that can mobilize endothelial progenitor cells after AKI are currently being tested. The inflammatory response in AKI, including activation of C5a, can be therapeutically targeted. Contemporary single cell profiling technologies have identified novel genes with altered expression, new signalling pathways and drug targets in AKI.

Recent advances in the pathogenesis of intrinsic AKI have provided a better understanding of the clinical continuum and the rational deployment of promising therapeutics.