Current issues in the prevention and management of oxidative stress in acute renal ischemic-reperfusion injury

Renal ischemia–reperfusion injury (IRI), which develops during organ-preserving kidney surgery and particularly during kidney transplantation (KT), remains a major challenge in urology and transplantology, as it can lead to progression of acute kidney injury and chronic graft dysfunction. Conservative strategies aimed at minimizing oxidative stress are especially important in situations where surgical options are limited. In transplantology, IRI is of particular relevance, as KT is the treatment of choice for patients with end-stage renal disease, significantly improving both quality of life and survival compared with renal replacement therapy. A critical stage of the transplantation procedure involves donor organ ischemia (warm and cold), followed by reperfusion after restoration of blood flow in the recipient. The severity of IRI directly influences graft function and is a key risk factor for delayed graft function and acute rejection [1, 2]. Therefore, the search for effective the search for to prevent and correct IRI is critical to improving kidney transplant outcomes.

Objective to systematize current knowledge on the potential of conservative methods for correcting renal IRI caused by excessive reactive oxygen species (ROS) during organ-preserving kidney surgery and KT under conditions of warm ischemia.

Methods. A systematic analysis of literature published over the past 10 years was conducted using the PubMed search engine, the Cochrane Library database of evidence-based medicine, and the Scopus unified bibliographic and abstract database of peer-reviewed scientific literature. Particular emphasis was placed on randomized studies evaluating drugs or newly synthesized compounds that suppress ROS formation and restore or enhance the body’s antioxidant capacity.

Conclusion. At the current stage of medical science, considerable attention is focused on substances capable of blocking the molecular mechanisms involved in mitochondrial membrane pore opening, as well as on agents that suppress ROS formation through inhibition of NADPH oxidase and xanthine oxidase. The therapeutic potential of exogenous enzyme preparations (such as superoxide dismutase and catalase), low-molecular-weight catalytic ROS scavengers, and non-enzymatic antioxidants – including supraphysiological doses of ascorbic acid and mitochondria-targeted agents such as mitoquinone and elamipretide – is actively being investigated. In the future, the results of these studies may form the basis for the development of effective antioxidant strategies for the prevention and treatment of renal IRI during organ-preserving kidney surgery and transplantation. 

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