Development of an in vitro Model of Ischemia Reperfusion Injury in Kidney Transplantation
Abstract
Kidney transplantation remains the optimal treatment option for patients with end-stage renal disease. We aim to improve organ preservation during transplantation by reducing damage from ischemia reperfusion injury (IRI) using existing clinically approved drugs. In this study, we developed and characterized an in vitro model that mimics the conditions of IRI in kidney transplant as a tool to screen and study the therapeutic effect of drugs in the context of IRI. We recapitulated several key outcomes in IRI in our model, including the induction of hypoxia, cell death, increased expression of damage markers (NGAL, HMBG-1) and pro-inflammatory cytokines in a sterile environment (IL-6, TNF- α). Additionally, we validated our model as a screening tool by testing select drugs for their ability to mitigate IRI. Overall, this study provides the foundation for further research that can improve organ preservation strategies, thereby increasing the quantity and quality of kidneys available for transplant.