Ischemia-Reperfusion Injury Reduces Long Term Renal Graft Survival: Mechanism and Beyond

Abstract

Ischemia-reperfusion injury (IRI) during renal transplantation often initiates non-specific inflammatory responses that can result in the loss of kidney graft viability. However, the long-term consequence of IRI on renal grafts survival is uncertain. Here we review clinical evidence and laboratory studies, and elucidate the association between early IRI and later graft loss. Our critical analysis of previous publications indicates that early IRI does contribute to later graft loss through reduction of renal functional mass, graft vascular injury, and chronic hypoxia, as well as subsequent fibrosis. IRI is also known to induce kidney allograft dysfunction and acute rejection, reducing graft survival. Therefore, attempts have been made to substitute traditional preserving solutions with novel agents, yielding promising results.

The efficacy of HBOC‐201 in ex situ gradual rewarming kidney perfusion in a rat model

“…It has been established that combination of warm and cold ischemia in DCD kidneys leads to severe ischemia reperfusion injury and subsequently increases the rate of delayed graft function after transplant and shortens long-term graft survival. 18 Urine production is the first sign of graft function after transplant and the urine volume may correlate with graft survival post-transplant. 19 Alongside urine volume, the quality of urine also plays an important role, for instance, GFR as a marker of renal glomerular function is used as a predictor factor of patient survival after kidney transplant.…”

Machine Perfusion of Extended Criteria Donor Organs: Immunological Aspects

“…IRI depends on several factors, including primary condition of the graft and length of cold and warm ischemia time (CIT and WIT). It additionally determines the extent of the inflammatory response and increases immunogenicity and the degree of microcirculatory perfusion failure during reperfusion resulting in early allograft dysfunction or primary non-function (3,4). As a link between the degree of IRI and activation of innate immunity (5) has been proposed, the discovery of new treatment strategies including tissue allorecognition pathways (Figure 1) has gained importance, especially in the era of extended criteria donor (ECD) organ Tx.…”

“…The direct pathway starts with recipient CD4 and CD8 T cells recognizing endogenous alloantigens presented by donor human leukocyte antigen (HLA) molecules on the surface of donor antigen-presenting cells (APCs) after their migration from the graft to the recipient's lymph nodes. This process is initiated by the massive release of pro-inflammatory cytokines from damaged cells during IRI (4). On the other hand, the indirect allorecognition relies on recipient-derived APCs, which ingest, process, and present alloantigens (typically HLA antigens) in the context of recipient HLA, for self-restricted recognition by recipient T cells (6,7).…”

Relaxin Positively Influences Ischemia—Reperfusion Injury in Solid Organ Transplantation: A Comprehensive Review

“…One possible solution for this problem is to extend the potential donor pool by using extended criteria donors (ECD) [10]. As these donors are older and have more comorbidities, organs are more prone to ischemia reperfusion injury (IRI) resulting in higher rates of delayed graft function, acute and chronic graft rejection and worse overall SOT outcomes [11][12][13][14][15]. There is a huge scientific effort to find ways in reducing IRI in order to increase the number of suitable organs procured from ECD.…”