Abstract
Thanks to the development of new, more potent and selective immunosuppressive drugs together with advances in surgical techniques, organ transplantation has emerged from an experimental surgery over fifty years ago to being the treatment of choice for many end-stage organ diseases, with over 139,000 organ transplants performed worldwide in 2019. Inherent to the transplantation procedure is the fact that the donor organ is subjected to blood flow cessation and ischemia during harvesting, which is followed by preservation and reperfusion of the organ once transplanted into the recipient. Consequently, ischemia/reperfusion induces a significant injury to the graft with activation of the immune response in the recipient and deleterious effect on the graft. The purpose of this review is to discuss and shed new light on the pathways involved in ischemia/reperfusion injury (IRI) that act at different stages during the donation process, surgery, and immediate post-transplant period. Here, we present strategies that combine various treatments targeted at different mechanistic pathways during several time points to prevent graft loss secondary to the inflammation caused by IRI.
Highlights
Organ shortage remains a major unresolved problem in organ transplantation
A recent study by Ritschl et al [89] explored the effect of perioperative perfusion of extended-criteria kidney allografts with anti-T lymphocyte globulin (ATG), which is used routinely as induction therapy to prevent graft rejection, and the results demonstrated a reduction of delayed graft function (DGF) and the need for dialysis in the short term, but no therapeutic effect was observed at 1-year follow-up
In the context of renal ischemia/reperfusion injury (IRI), a recent study by Yan et al [107] evaluated the role of myeloid-derived suppressor cells (MDSCs) using an experimental model and found that after induction by granulocyte colony-stimulating factor (G-CSF), MDSC secrete arginase-1 (ARG-1), which prevents T cell proliferation and potent immune responses
Summary
Organ shortage remains a major unresolved problem in organ transplantation. There is an increasing demand for organ transplantation worldwide, but there are not enough organs to meet the increasing demand. To increase the pool of organs available for transplantation the use of extended criteria to include donation after circulatory death (DCD) has been recently adopted [1,2] Greatly needed, these extended-criteria organs are known to suffer from more ischemic damage, which is in turn associated with suboptimal results [3,4]. ROS mediates lipid peroxidation and destruction of the cell membrane bilayer, while the calcium increase inside mitochondria leads to membrane instability and the release of cytochrome C All these processes induce cell death during IRI [13]
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