Effects of Ischemia and Reperfusion Injury on Long-Term Graft Function

Requião-Moura, Lúcio R.; Durão, Marcelino de Souza; Tonato, Eduardo José; Matos, Acc; Ozaki, Kikumi S.; Câmara, Niels Olsen Saraiva; Pacheco-Silva, Álvaro

doi:10.1016/j.transproceed.2010.12.012

Cited by 23 publications

(23 citation statements)

References 21 publications

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“…The relatively high (62%) incidence of DGF in the recipients of DD kidneys in the present study was similar to that found (57%) in another multicentric study in Brazilian patients (2). We believe that the main reason for this relatively high incidence of DGF in Brazil is related to deceased donor conditions, particularly before the diagnosis of brain death.…”

Section: Discussionsupporting

confidence: 89%

Investigation of Apoptosis-Related Gene Expression Levels in Preimplantation Biopsies as Predictors of Delayed Kidney Graft Function

Goncalves-Primo¹,

Mourão²,

Andrade-Oliveira³

et al. 2014

Transplantation

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Section: Discussionsupporting

confidence: 89%

Investigation of Apoptosis-Related Gene Expression Levels in Preimplantation Biopsies as Predictors of Delayed Kidney Graft Function

Goncalves-Primo¹,

Mourão²,

Andrade-Oliveira³

et al. 2014

Transplantation

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“…Components of IRI which contribute to adverse transplant outcomes include inflammation, reactive oxygen species production (ROS), necrosis, apoptosis, and thrombosis (2,3). ROS production, an immediate response to ischemia/reperfusion, triggers or amplifies many downstream processes including vasoconstriction and thrombosis that further deprive the graft organ of oxygen and nutrients.…”

Section: Introductionmentioning

confidence: 99%

CD47 Blockade Reduces Ischemia-Reperfusion Injury and Improves Outcomes in a Rat Kidney Transplant Model

Lin¹,

Manning²,

Jia³

et al. 2014

Transplantation

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Background Ischemia/reperfusion injury (IRI) significantly contributes to delayed graft function and inflammation leading to graft loss. IRI is exacerbated by the thrombospondin-1/CD47 system through inhibition of nitric oxide signaling. We postulate that CD47 blockade and prevention of nitric oxide inhibition reduces IRI in organ transplantation. Methods We used a syngeneic rat renal transplantation model of IRI with bilaterally nephrectomized recipients to evaluate the effect of a CD47 monoclonal antibody (CD47mAb) on IRI. Donor kidneys were flushed with CD47mAb OX101 or an isotype-matched control immunoglobulin and stored at 4°C in UW solution for 6 hours prior to transplantation. Results CD47mAb perfusion of donor kidneys resulted in marked improvement in post-transplant survival, lower levels of serum creatinine, BUN, phosphorus and magnesium and less histologic evidence of injury. In contrast, control groups did not survive more than 5 days, had increased biochemical indicators of renal injury and exhibited severe pathological injury with tubular atrophy and necrosis. Recipients of CD47mAb-treated kidneys showed decreased levels of plasma biomarkers of renal injury including cystatin C, osteopontin, TIMP1, β2-microglobulin, VEGF-A and clusterin compared to the control group. Furthermore, laser Doppler assessment showed higher renal blood flow in the CD47mAb-treated kidneys. Conclusions These results provide strong evidence for the use of CD47 antibody-mediated blockade to reduce IRI and improve organ preservation for renal transplantation.

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“…Renal IRI induces acute kidney injury (AKI) and is seen in many clinical situations, including kidney transplantation (80,81) and cardiac surgery-associated AKI (29,42,78). In kidney transplantation, severe ischemic injury in donor kidneys from donation after cardiac death is a primary reason for either exclusion (2) or delayed graft function (10,91) and is a high risk factor for both acute and chronic allograft rejection (75,86) and graft loss (39,75,96). Cardiac surgery-associated AKI is characterized by an abrupt reduction in the glomerular filtration rate of the kidney after cardiac surgery (5,78) and may contribute to the increased mortality as a small (0.3-0.5 mg/dl) or larger (Ͼ0.5 mg/dl) increase in serum creatinine after cardiac surgery correlates with a nearly 3-or 18-fold increase in 30-day mortality, respectively (42).…”

mentioning

confidence: 99%

Requirement of clusterin expression for prosurvival autophagy in hypoxic kidney tubular epithelial cells

Alnasser

Guan

Zhang³

et al. 2016

American Journal of Physiology-Renal Physiology

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Cellular autophagy is a prosurvival mechanism in the kidney against ischemia-reperfusion injury (IRI), but the molecular pathways that activate the autophagy in ischemic kidneys are not fully understood. Clusterin (CLU) is a chaperone-like protein, and its expression is associated with kidney resistance to IRI. The present study investigated the role of CLU in prosurvival autophagy in the kidney. Renal IRI was induced in mice by clamping renal pedicles at 32°C for 45 min. Hypoxia in renal tubular epithelial cell (TEC) cultures was induced by exposure to a 1% O2 atmosphere. Autophagy was determined by either light chain 3-BII expression with Western blot analysis or light chain 3-green fluorescent protein aggregation with confocal microscopy. Cell apoptosis was determined by flow cytometric analysis. The unfolded protein response was determined by PCR array. Here, we showed that autophagy was significantly activated by IRI in wild-type (WT) but not CLU-deficient kidneys. Similarly, autophagy was activated by hypoxia in human proximal TECs (HKC-8) and WT mouse primary TECs but was impaired in CLU-null TECs. Hypoxia-activated autophagy was CLU dependent and positively correlated with cell survival, and inhibition of autophagy significantly promoted cell death in both HKC-8 and mouse WT/CLU-expressing TECs but not in CLU-null TECs. Further experiments showed that CLU-dependent prosurvival autophagy was associated with activation of the unfolded protein response in hypoxic kidney cells. In conclusion, these data suggest that activation of prosurvival autophagy by hypoxia in kidney cells requires CLU expression and may be a key cytoprotective mechanism of CLU in the protection of the kidney from hypoxia/ischemia-mediated injury.

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Effects of Ischemia and Reperfusion Injury on Long-Term Graft Function

Cited by 23 publications

References 21 publications

Investigation of Apoptosis-Related Gene Expression Levels in Preimplantation Biopsies as Predictors of Delayed Kidney Graft Function

Investigation of Apoptosis-Related Gene Expression Levels in Preimplantation Biopsies as Predictors of Delayed Kidney Graft Function

CD47 Blockade Reduces Ischemia-Reperfusion Injury and Improves Outcomes in a Rat Kidney Transplant Model

Requirement of clusterin expression for prosurvival autophagy in hypoxic kidney tubular epithelial cells

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