Exploration of Repositioned Drugs in the Management of Renal Ischemia Reperfusion Injury.
Abstract
Recent evidence demonstrates that oxygenated perfusion at 22°C is superior to static cold storage for preserving pre-transplanted kidneys; nonetheless, there is opportunity for improvement. Therefore, we aim to repurpose existing off-patent drugs in combination with oxygenated perfusion to further reduce organ damage caused by ischemia reperfusion injury. Through the development and characterization of both cold and room temperature injury models, the room temperature-based model demonstrated decreased pro-inflammatory cytokines and increased cell viability compared to previously developed cold IRI model. These findings provide evidence that the room temperature-based model can not only mitigate the risk associated with cold IRI, but also serve as a viable platform for conducting large-scale drug repositioning studies. Piloting this model for a small-scale drug screening, we identified several candidates with potential anti-inflammatory properties applicable to mitigating IRI. Consequently, the development of a novel preservation system can increase the availability of healthy donor kidneys for transplant and enhance patient long-term outcomes.