The Impact of Ischemia and Reperfusion Injury in Kidney Allograft Outcome

Bueno, Valquíria

doi:10.5772/22067

Cited by 2 publications

(2 citation statements)

References 85 publications

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“…8) demonstrate a nephroprotective function for selective intrarenal LepA treatment in kidney IR injury. This approach may have far-reaching clinical implications for kidney revascularization under multiple clinical circumstances, including transplantation of allograft cadaveric kidneys [40]. Unlike studies utilizing systemic administration of leptin preceding ischemia, tissue protection in our system involves intervention post-IR, which is consistent with clinical scenarios.…”

Section: Discussionmentioning

confidence: 99%

Intrarenal Anti-Leptin Treatment Attenuates Ischemia and Reperfusion Injury

Jonas¹,

Simon²,

Gilburd³

et al. 2023

Am J Nephrol

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Introduction: Renal ischemia and reperfusion (IR) injury introduces cellular stress and is the main cause of acute kidney damage. Renal cells exposed to noxious stress induce the expression of the pleiotropic hormone leptin. As we have previously revealed a deleterious stress-related role for leptin expression, these results suggested that leptin is also involved in pathological renal remodeling. The systemic functions of leptin preclude the study of its local effects using conventional approaches. We have therefore designed a method to locally perturb leptin activity in specific tissues without affecting its systemic levels. This study explores whether local anti-leptin strategy is renoprotective in a post-IR porcine kidney model. Methods: We induced renal IR injury in pigs by exposing kidneys to ischemia and revascularization. Upon reperfusion, kidneys instantly received an intra-arterial bolus of either a leptin antagonist (LepA) or saline solution. Peripheral blood was sampled to assess systemic leptin, IL-6, creatinine, and BUN levels, and postoperative tissue samples were analyzed by hematoxylin and eosin histochemistry and immunohistochemistry. Results: Histology of IR/saline kidneys exhibited extensive necrosis of proximal tubular epithelial cells, as well as elevated levels of apoptosis markers and inflammation. In contrast, IR/LepA kidneys showed no signs of necrosis or inflammation with normal IL-6 and tall-like receptor 4 levels. LepA treatment led to upregulation in mRNA levels of leptin, leptin receptor, ERK1/2, STAT3, and transport molecule Na/H exchanger-3. Conclusions: Local, intrarenal postischemic LepA treatment at reperfusion prevented apoptosis and inflammation and was renoprotective. Selective intrarenal administration of LepA at reperfusion may provide a viable option for clinical implementation.

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Section: Discussionmentioning

confidence: 99%

Intrarenal Anti-Leptin Treatment Attenuates Ischemia and Reperfusion Injury

Jonas¹,

Simon²,

Gilburd³

et al. 2023

Am J Nephrol

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“…Furthermore, the medical complications of CKD may lead to end-stage renal disease. Dialysis and kidney transplant are the only treatments available for CKD and end-stage renal disease, with transplants being considered the more sustainable alternative in terms of long-term survival rates, especially among patients with end-stage renal disease. , Unfortunately, kidney donations for transplants are outnumbered by the patients with end-stage renal disease. Therefore, health authorities have increased the donor pool by extending the donor criteria and adopting ex vivo normothermic perfusion technologies.…”

Section: Introductionmentioning

confidence: 99%

Renal Hypoxic Reperfusion Injury-on-Chip Model for Studying Combinational Vitamin Therapy

Salih

Asif

Samantasinghar

et al. 2022

ACS Biomater. Sci. Eng.

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Renal ischemic-reperfusion injury decreases the chances of long-term kidney graft survival and may lead to the loss of a transplanted kidney. During organ excision, the cycle of warm ischemia from the donor and cold ischemia is due to storage in a cold medium after revascularization following organ transplantation. The reperfusion of the kidney graft activates several pathways that generate reactive oxygen species, forming a hypoxic-reperfusion injury. Animal models are generally used to model and investigate renal hypoxic-reperfusion injury. However, these models face ethical concerns and present a lack of robustness and intraspecies genetic variations, among other limitations. We introduce a microfluidics-based renal hypoxic-reperfusion (RHR) injury-on-chip model to overcome current limitations. Primary human renal proximal tubular epithelial cells and primary human endothelial cells were cultured on the apical and basal sides of a porous membrane. Hypoxic and normoxic cell culture media were used to create the RHR injury-on-chip model. The disease model was validated by estimating various specific hypoxic biomarkers of RHR. Furthermore, retinol, ascorbic acid, and combinational doses were tested to devise a therapeutic solution for RHR. We found that combinational vitamin therapy can decrease the chances of RHR injury. The proposed RHR injury-on-chip model can serve as an alternative to animal testing for injury investigation and the identification of new therapies.

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The Impact of Ischemia and Reperfusion Injury in Kidney Allograft Outcome

Cited by 2 publications

References 85 publications

Intrarenal Anti-Leptin Treatment Attenuates Ischemia and Reperfusion Injury

Intrarenal Anti-Leptin Treatment Attenuates Ischemia and Reperfusion Injury

Renal Hypoxic Reperfusion Injury-on-Chip Model for Studying Combinational Vitamin Therapy

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