Assessing Kidney Graft Viability and Its Cells Metabolism during Machine Perfusion

Bellini, Maria Irene; Tortorici, F.; Amabile, Maria Ida; D’Andrea, Vito

doi:10.3390/ijms22031121

Cited by 20 publications

(17 citation statements)

References 84 publications

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“…Our data also indicate that, at the immediate post-transplantation period, ischemia-reperfusion injury may increase the antigenicity of the kidney graft. Hence, efforts to alleviate kidney transplant ischemia-reperfusion injury by evolving and applying more efficient preservation methods may be proven beneficial [52]. Finally, our study showed that ischemiareperfusion increases RPTECs' antigenicity by enhancing ICAM-1 expression.…”

Section: Discussionmentioning

confidence: 59%

A Role for Human Renal Tubular Epithelial Cells in Direct Allo-Recognition by CD4+ T-Cells and the Effect of Ischemia-Reperfusion

Eleftheriadis

Pissas

Crespo

et al. 2021

IJMS

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Direct allorecognition is the earliest and most potent immune response against a kidney allograft. Currently, it is thought that passenger donor professional antigen-presenting cells (APCs) are responsible. Further, many studies support that graft ischemia-reperfusion injury increases the probability of acute rejection. We evaluated the possible role of primary human proximal renal tubular epithelial cells (RPTECs) in direct allorecognition by CD4+ T-cells and the effect of anoxia-reoxygenation. In cell culture, we detected that RPTECs express all the required molecules for CD4+ T-cell activation (HLA-DR, CD80, and ICAM-1). Anoxia-reoxygenation decreased HLA-DR and CD80 but increased ICAM-1. Following this, RPTECs were co-cultured with alloreactive CD4+ T-cells. In T-cells, zeta chain phosphorylation and c-Myc increased, indicating activation of T-cell receptor and co-stimulation signal transduction pathways, respectively. T-cell proliferation assessed with bromodeoxyuridine assay and with the marker Ki-67 increased. Previous culture of RPTECs under anoxia raised all the above parameters in T-cells. FOXP3 remained unaffected in all cases, signifying that proliferating T-cells were not differentiated towards a regulatory phenotype. Our results support that direct allorecognition may be mediated by RPTECs even in the absence of donor-derived professional APCs. Also, ischemia-reperfusion injury of the graft may enhance the above capacity of RPTECs, increasing the possibility of acute rejection.

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Section: Discussionmentioning

confidence: 59%

A Role for Human Renal Tubular Epithelial Cells in Direct Allo-Recognition by CD4+ T-Cells and the Effect of Ischemia-Reperfusion

Eleftheriadis

Pissas

Crespo

et al. 2021

IJMS

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“…In hypothermic conditions, options to assess kidney function are limited. Indeed, the metabolic rate at 4°C is limited to 10% of that at physiological temperature with a 40% lower rate of chemical reactions ( 24 ). Furthermore, in the majority of cases there is no active oxygenation during hypothermic kidney perfusion in which case aerobic metabolism is not supported ( 25 ).…”

Section: Kidneymentioning

confidence: 99%

Sense and Sensibilities of Organ Perfusion as a Kidney and Liver Viability Assessment Platform

Verstraeten¹,

Jochmans

2022

Transpl Int

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Predicting organ viability before transplantation remains one of the most challenging and ambitious objectives in transplant surgery. Waitlist mortality is high while transplantable organs are discarded. Currently, around 20% of deceased donor kidneys and livers are discarded because of “poor organ quality”, Decisions to discard are still mainly a subjective judgement since there are only limited reliable tools predictive of outcome available. Organ perfusion technology has been posed as a platform for pre-transplant organ viability assessment. Markers of graft injury and function as well as perfusion parameters have been investigated as possible viability markers during ex-situ hypothermic and normothermic perfusion. We provide an overview of the available evidence for the use of kidney and liver perfusion as a tool to predict posttransplant outcomes. Although evidence shows post-transplant outcomes can be predicted by both injury markers and perfusion parameters during hypothermic kidney perfusion, the predictive accuracy is too low to warrant clinical decision making based upon these parameters alone. In liver, further evidence on the usefulness of hypothermic perfusion as a predictive tool is needed. Normothermic perfusion, during which the organ remains fully metabolically active, seems a more promising platform for true viability assessment. Although we do not yet fully understand “on-pump” organ behaviour at normothermia, initial data in kidney and liver are promising. Besides the need for well-designed (registry) studies to advance the field, the catch-22 of selection bias in clinical studies needs addressing.

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“…Cell metabolism correlates closely with perfusion; therefore, in IRI, metabolism becomes deranged and can lead to alterations in the electron transport chain as well as increased levels of ROS. When damage remains below a certain threshold, the renal tubules are able to repair the damage, mitigating the loss of functioning parenchyma and glomerular filtration ability [ 100 ]. Therefore, as essential as reperfusion is for cell survival, it is this same reperfusion that can also accelerate the apoptotic pathways in IRI.…”

Section: Literature Searchmentioning

confidence: 99%

Cancer Metabolism and Ischemia-Reperfusion Injury: Two Sides of the Same Coin

Nemeth

Baldini

Sorrenti

et al. 2022

JCM

Self Cite

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Cancer cells are characterized by the reprogramming of certain cell metabolisms via activation of definite pathways and regulation of gene signaling. Ischemia-reperfusion injury (IRI) is characterized by tissue damage and death following a lack of perfusion and oxygenation. It is most commonly seen in the setting of organ transplantation. Interestingly, the microenvironments seen in cancer and ischemic tissues are quite similar, especially due to the hypoxic state that occurs in both. As a consequence, there is genetic signaling involved in response to IRI that has common pathways with cancer. Some of these changes are seen across the board with many cancer cells and are known as Hallmarks of Cancer, among which are aerobic glycolysis and the induction of angiogenesis. This literature review aims to compare the metabolic pathways that are altered in cancer tissues and in normal tissues subjected to IRI in order to find common adaptive processes and to identify key pathways that could represent a therapeutic target in both pathologies. By increasing our understanding of this relationship, clinical correlations can be made and applied practically to improve outcomes of transplanted organs, given the known association with acute rejection, delayed graft function, and poor graft survival. The following metabolic pathways are discussed in our review, both in the setting of cancer and IRI: apoptosis, glycolysis, and angiogenesis. The role of the immune system in both pathologies as well as mitochondrial function and the production of reactive oxygen species (ROS) are reviewed.

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Assessing Kidney Graft Viability and Its Cells Metabolism during Machine Perfusion

Cited by 20 publications

References 84 publications

A Role for Human Renal Tubular Epithelial Cells in Direct Allo-Recognition by CD4+ T-Cells and the Effect of Ischemia-Reperfusion

A Role for Human Renal Tubular Epithelial Cells in Direct Allo-Recognition by CD4+ T-Cells and the Effect of Ischemia-Reperfusion

Sense and Sensibilities of Organ Perfusion as a Kidney and Liver Viability Assessment Platform

Cancer Metabolism and Ischemia-Reperfusion Injury: Two Sides of the Same Coin

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