How to Best Protect Kidneys for Transplantation—Mechanistic Target

The increasing number of patients on the kidney transplant waiting list underlines the need to expand the donor pool and improve kidney graft utilization. By protecting kidney grafts adequately from the initial ischemic and subsequent reperfusion injury occurring during transplantation, both the number and quality of kidney grafts could be improved. The last few years have seen the emergence of many new technologies to abrogate ischemia–reperfusion (I/R) injury, including dynamic organ preservation through machine perfusion and organ reconditioning therapies. Although machine perfusion is gradually making the transition to clinical practice, reconditioning therapies have not yet progressed from the experimental setting, pointing towards a translational gap. In this review, we discuss the current knowledge on the biological processes implicated in I/R injury and explore the strategies and interventions that are being proposed to either prevent I/R injury, treat its deleterious consequences, or support the reparative response of the kidney. Prospects to improve the clinical translation of these therapies are discussed with a particular focus on the need to address multiple aspects of I/R injury to achieve robust and long-lasting protective effects on the kidney graft.