Exploring the Immunological Landscape of Ischemia/Reperfusion Injury and Graft Rejection in Kidney Transplantation: Shared Mechanisms and Insights

Background: Ischemia/reperfusion injury (IRI) is considered one of the major risk factors involved in the development of delayed graft function that significantly impacts both the early and long-term function of allografts due to its harmful effects on cells. Purpose: This narrative review aims to explore the emerging aspects of IRI in organ transplantation, focusing on the still unclear relationships between IRI and the development of both T-cell-mediated and/or antibody-mediated rejections. Key findings: Recently, efforts aimed at increasing the knowledge of the mechanisms involved have revealed that IRI is connected to rejection processes through a complex of interconnected pathways. These pathways affect both the viability and the metabolism of immune cells, ultimately influencing graft outcomes. Therefore, these pathways demonstrate the complexity of immune responses after transplantation and play a role in both acute and chronic rejection processes. Conclusions: Improving graft outcomes requires an understanding of the multifaceted relationship between IRI and immune-mediated rejection, which is critical to improve graft outcomes. Further research is needed to clarify these mechanisms and develop targeted strategies to mitigate IRI and its impact on transplant rejection.