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Review
. 2019 Jun;34(6):951-963.
doi: 10.1007/s00467-018-3940-4. Epub 2018 Mar 30.

Ischaemia reperfusion injury: mechanisms of progression to chronic graft dysfunction

Gerhard R Situmorang  1   2 , Neil S Sheerin  3
Affiliations
Review

Ischaemia reperfusion injury: mechanisms of progression to chronic graft dysfunction

Gerhard R Situmorang et al. Pediatr Nephrol. 2019 Jun.

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.

Keywords: Acute ischaemic injury; Chronic graft dysfunction; Delayed graft function; Endothelial dysfunction; HIF-1; Hypoxia; Kidney transplantation.

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Conflict of interest statement

The authors declare that they have no conflict of interest.

Figures

Fig. 1
Fig. 1
Mechanisms proposed in the development of chronic graft dysfunction. IRI ischaemia-reperfusion injury
Fig. 2
Fig. 2
HIF-α canonical pathway during a normoxia and b hypoxia
Fig. 3
Fig. 3
Contribution of HIF-α to the development of post-ischaemic fibrosis
Fig. 4
Fig. 4
Mechanical obstruction of the capillary network and reduction in blood vessel patency
Fig. 5
Fig. 5
Kidney tubular epithelial cells playing an active role in progression of post-ischaemic tissue damage through several mechanisms
Fig. 6
Fig. 6
Factors that can be modified to prevent the progression of acute IRI to chronic graft dysfunction. IRI ischaemia-reperfusion injury
See this image and copyright information in PMC

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