TY - JOUR
T1 - Ischaemia reperfusion injury
T2 - mechanisms of progression to chronic graft dysfunction
AU - Situmorang, Gerhard R.
AU - Sheerin, Neil S.
N1 - Publisher Copyright:
© 2018, The Author(s).
PY - 2019/6/1
Y1 - 2019/6/1
N2 - 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.
AB - 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.
KW - Acute ischaemic injury
KW - Chronic graft dysfunction
KW - Delayed graft function
KW - Endothelial dysfunction
KW - HIF-1
KW - Hypoxia
KW - Kidney transplantation
UR - http://www.scopus.com/inward/record.url?scp=85044573815&partnerID=8YFLogxK
U2 - 10.1007/s00467-018-3940-4
DO - 10.1007/s00467-018-3940-4
M3 - Review article
C2 - 29603016
AN - SCOPUS:85044573815
SN - 0931-041X
VL - 34
SP - 951
EP - 963
JO - Pediatric Nephrology
JF - Pediatric Nephrology
IS - 6
ER -