Pathogenesis of intrinsic acute kidney injury

Abstract

Purpose of reviewThis review focuses on the pathogenesis of intrinsic acute kidney injury (AKI), emphasizing recent advances that hold therapeutic promise.Recent findingsEnhanced 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.SummaryRecent advances in the pathogenesis of intrinsic AKI have provided a better understanding of the clinical continuum and the rational deployment of promising therapeutics.

The impact of statin use before intensive care unit admission on patients with acute kidney injury after cardiac surgery

“…Statins directly act on endothelial cells by enhancing their ability to generate nitric oxide (NO) and upregulate nitric oxide synthase (eNOS) (Laufs et al, 1997;Kureishi et al, 2000). Research has reported that the use of endothelin receptor antagonists or supplementation with NO can block the enhancement of endothelin and the reduction of endothelial-derived NO release in AKI (Devarajan, 2023). The role of preoperative statin treatment was controversial in reducing the incidence of CKA-AKI or mortality (Argalious et al, 2010;Park et al, 2016;Zheng et al, 2016).…”