Ischaemia reperfusion injury: mechanisms of progression to chronic graft dysfunction

Abstract

The increasing use of extended criteria organs to meet the demand for kidney transplantation raises an important question of how the severity of early ischaemic injury influences long-term outcomes. Significant acute ischaemic kidney injury is associated with delayed graft function, increased immune-associated events and, ultimately, earlier deterioration of graft function. A comprehensive understanding of immediate molecular events that ensue post-ischaemia and their potential long-term consequences are key to the discovery of novel therapeutic targets. Acute ischaemic injury primarily affects tubular structure and function. Depending on the severity and persistence of the insult, this may resolve completely, leading to restoration of normal function, or be sustained, resulting in persistent renal impairment and progressive functional loss. Long-term effects of acute renal ischaemia are mediated by several mechanisms including hypoxia, HIF-1 activation, endothelial dysfunction leading to vascular rarefaction, sustained pro-inflammatory stimuli involving innate and adaptive immune responses, failure of tubular cells to recover and epigenetic changes. This review describes the biological relevance and interaction of these mechanisms based on currently available evidence.

The Effects of Ascorbic Acid and U-74389G on Renal Ischemia-Reperfusion Injury in a Rat Model

“…According to experimental studies, targeting inflammatory pathways has a protective action in rodents; conversely, clinical studies have shown that targeting the same pathways in humans has no therapeutic effect. Moreover, bridging the underlying mechanisms of acute rejection and ischemic graft injury with intervention with novel therapeutic agents would be of paramount importance (42,43).…”

Long Noncoding RNA/Circular RNA-miRNA-mRNA Axes in Ischemia-Reperfusion Injury

“…Renal IRI, which contributes greatly to AKI, is one of the most critical issues for many clinical situations, including renal transplantation, nephrectomy, sepsis, and repair of suprarenal aneurism [ 129 – 131 ]. Hu et al [ 132 ] used a microarray assay to find that 2218 genes are differentially expressed in renal IRI, including 1103 upregulated genes and 1115 downregulated genes.…”

Identification of Candidate Genes Involved in Renal Ischemia/Reperfusion Injury

“…IRI is one of the most important but unavoidable risk factors for causing the impairment of graft function. Renal IRI triggers the generation of reactivate oxygen species, causing oxidative injury, acute inflammation and eventually necrosis, and apoptosis of renal tubular epithelial cells (Gu et al , 2018 ; Situmorang and Sheerin, 2018 ). These responses can evoke the anti-inflammatory and repair processes to initiate the recovery of the graft function (Sanchez-Nino et al , 2016 ; Pressly and Park, 2017 ).…”