scholarly journals Barriers and Advances in Kidney Preservation

2018 ◽  
Vol 2018 ◽  
pp. 1-15 ◽  
Author(s):  
C. Steichen ◽  
S. Giraud ◽  
D. Bon ◽  
B. Barrou ◽  
L. Badet ◽  
...  
Keyword(s):  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Kidney Graft ◽  
Kidney Preservation ◽  
Preservation Method ◽  
New Concepts ◽  
Organ Quality ◽  
Short And Long Term ◽  
Oxygen Addition ◽  
Definition Of

Despite the fact that a significant fraction of kidney graft dysfunctions observed after transplantation is due to ischemia-reperfusion injuries, there is still no clear consensus regarding optimal kidney preservation strategy. This stems directly from the fact that as of yet, the mechanisms underlying ischemia-reperfusion injury are poorly defined, and the role of each preservation parameter is not clearly outlined. In the meantime, as donor demography changes, organ quality is decreasing which directly increases the rate of poor outcome. This situation has an impact on clinical guidelines and impedes their possible harmonization in the transplant community, which has to move towards changing organ preservation paradigms: new concepts must emerge and the definition of a new range of adapted preservation method is of paramount importance. This review presents existing barriers in transplantation (e.g., temperature adjustment and adequate protocol, interest for oxygen addition during preservation, and clear procedure for organ perfusion during machine preservation), discusses the development of novel strategies to overcome them, and exposes the importance of identifying reliable biomarkers to monitor graft quality and predict short and long-term outcomes. Finally, perspectives in therapeutic strategies will also be presented, such as those based on stem cells and their derivatives and innovative models on which they would need to be properly tested.

scholarly journals In Vitro/Ex Vivo Models for the Study of Ischemia Reperfusion Injury during Kidney Perfusion

2020 ◽  
Vol 21 (21) ◽  
pp. 8156
Author(s):  
Sebastien Giraud ◽  
Raphaël Thuillier ◽  
Jérome Cau ◽  
Thierry Hauet
Keyword(s):  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ex Vivo ◽  
Ischemia Reperfusion ◽  
Kidney Graft ◽  
Kidney Preservation ◽  
Hypothermic Machine Perfusion ◽  
Kidney Perfusion ◽  
Marginal Donors

Oxidative stress is a key element of ischemia–reperfusion injury, occurring during kidney preservation and transplantation. Current options for kidney graft preservation prior to transplantation are static cold storage (CS) and hypothermic machine perfusion (HMP), the latter demonstrating clear improvement of preservation quality, particularly for marginal donors, such as extended criteria donors (ECDs) and donation after circulatory death (DCDs). Nevertheless, complications still exist, fostering the need to improve kidney preservation. This review highlights the most promising avenues of in kidney perfusion improvement on two critical aspects: ex vivo and in vitro evaluation.

Immune Responses in Kidney Preservation and Reperfusion Injury

2004 ◽  
Vol 52 (5) ◽  
pp. 310-314 ◽  
Author(s):  
Niamh E. Kieran ◽  
Hamid Rabb
Keyword(s):  
Reperfusion Injury ◽  
Organ Preservation ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Organ Transplant ◽  
Experimental Models ◽  
Kidney Preservation ◽  
Immune Mediators ◽  
Preservation Injury ◽  
Short And Long Term

Organ preservation and reperfusion injury have significant detrimental effects on both short- and long-term organ function. Ischemia reperfusion injury (IRI) underlies organ transplant dysfunction, myocardial infarction, stroke, and shock. Multiple molecular pathways are engaged in reactive oxygen production, apoptosis, signaling, and tissue regeneration. There has been an increased understanding of the important role of immune and inflammatory pathways in IRI, both in humans and in experimental models. Both cellular and soluble components of the immune system are directly activated during IRI, and there is evidence that immune mediators directly contribute to organ dysfunction. Immune activation during IRI likely underlies the enhanced immunogenicity of ischemic organs, with resultant increased rejection and fibrosis. Novel human therapies targeting T and B cells for classic immune diseases can now be considered to prevent and treat IRI. Organ preservation injury and cold ischemia could well have distinct pathophysiology from warm IRI and represent an opportunity to develop improved preservation methods.

scholarly journals Ex-vivo Kidney Machine Perfusion: Therapeutic Potential

2021 ◽  
Vol 8 ◽  
Author(s):  
Ruta Zulpaite ◽  
Povilas Miknevicius ◽  
Bettina Leber ◽  
Kestutis Strupas ◽  
Philipp Stiegler ◽  
...  
Keyword(s):  
Kidney Transplantation ◽  
Clinical Practice ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ex Vivo ◽  
Ischemia Reperfusion ◽  
Graft Function ◽  
Kidney Graft ◽  
Machine Perfusion ◽  
Kidney Preservation

Kidney transplantation remains the gold standard treatment for patients suffering from end-stage kidney disease. To meet the constantly growing organ demands grafts donated after circulatory death (DCD) or retrieved from extended criteria donors (ECD) are increasingly utilized. Not surprisingly, usage of those organs is challenging due to their susceptibility to ischemia-reperfusion injury, high immunogenicity, and demanding immune regulation after implantation. Lately, a lot of effort has been put into improvement of kidney preservation strategies. After demonstrating a definite advantage over static cold storage in reduction of delayed graft function rates in randomized-controlled clinical trials, hypothermic machine perfusion has already found its place in clinical practice of kidney transplantation. Nevertheless, an active investigation of perfusion variables, such as temperature (normothermic or subnormothermic), oxygen supply and perfusate composition, is already bringing evidence that ex-vivo machine perfusion has a potential not only to maintain kidney viability, but also serve as a platform for organ conditioning, targeted treatment and even improve its quality. Many different therapies, including pharmacological agents, gene therapy, mesenchymal stromal cells, or nanoparticles (NPs), have been successfully delivered directly to the kidney during ex-vivo machine perfusion in experimental models, making a big step toward achievement of two main goals in transplant surgery: minimization of graft ischemia-reperfusion injury and reduction of immunogenicity (or even reaching tolerance). In this comprehensive review current state of evidence regarding ex-vivo kidney machine perfusion and its capacity in kidney graft treatment is presented. Moreover, challenges in application of these novel techniques in clinical practice are discussed.

Abstract 403: Leveraging the Zebrafish to Overcome Barriers in Heart Transplantation

2020 ◽  
Vol 127 (Suppl_1) ◽  
Author(s):  
Shannon N Tessier ◽  
Luciana Da Silveira Cavalcante ◽  
Casie A Pendexter ◽  
Stephanie E Cronin ◽  
Reinier J de Vries ◽  
...  
Keyword(s):  
Heart Transplantation ◽  
Ischemia Reperfusion Injury ◽  
Ex Vivo ◽  
Ischemia Reperfusion ◽  
Complex Structure ◽  
Scale Up ◽  
Adult Zebrafish ◽  
Zebrafish Larvae ◽  
Preservation Method ◽  
Heart Preservation

Cardiac transplantation is the only curative therapy for patients with end-stage heart disease; however, there is a severe shortage of viable donor organs. Heart transplantation faces many interwoven challenges, including both biological factors and research limitations. For example, ischemia-reperfusion injury plays a role in early graft dysfunction and is associated with rejection episodes in heart transplantation. Moreover, experimental transplantation relies heavily on animal studies that are laborious and expensive, prohibiting the discovery of novel, bold solutions. We propose that the zebrafish, Danio rerio , would be a valuable tool for the field since it’s amenable to high-throughput screens, captures the complex structure of organs, and offers a suite of tools to monitor the biology of cardiac injury. Here, we develop a new subzero heart preservation method by strategically leveraging animal models from zebrafish to mammalian hearts. Using zebrafish larvae, we screened for agents which preserve hearts at -10°C. As a result of these screens, we identified promising preservative cocktails which restored heartbeat in 82% of larvae immediately post-recovery. Next, we excised adult zebrafish hearts and developed methods to mimic the ex vivo handling practices of hearts destined for transplant using a heart-on-a-plate assay. Using this assay, we carried forward promising agents identified in our initial zebrafish larvae screen to isolated adult zebrafish hearts that were cooled to -10°C and held for up to 24 hours. After rewarming, heart rate was restored and metabolic rate of zebrafish hearts was like time-matched controls (0.213 ± 0.047 and 0.275 ± 0.060, respectively, p = 0.200). Finally, we report our preliminary scale-up efforts whereby rodent hearts are stored for up to 24 hours at -10°C and viability were assessed by the TUNEL assay. The data shows high viability of cardiomyocytes post-preservation, as compared to controls. In summary, we present data to illustrate our efforts in leveraging the zebrafish to aid new discoveries in subzero heart preservation. Similar efforts to model heart transplantation in zebrafish may provide a different vantage point and enable us to make advances faster.

Ischemia—reperfusion injury as a risk factor for late kidney graft failure

1997 ◽  
pp. 77-83 ◽  
Author(s):  
J. M. Grinyó ◽  
S. Gil-Vernet ◽  
F. Moreso ◽  
D. Serón ◽  
X. Fulladosa ◽  
...  
Keyword(s):  
Risk Factor ◽  
Reperfusion Injury ◽  
Graft Failure ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Kidney Graft

scholarly journals Therapeutic Potential of Selenium as a Component of Preservation Solutions for Kidney Transplantation

Molecules ◽  
2020 ◽  
Vol 25 (16) ◽  
pp. 3592
Author(s):  
Aneta Ostróżka-Cieślik ◽  
Barbara Dolińska ◽  
Florian Ryszka
Keyword(s):  
Reperfusion Injury ◽  
Activity Concentration ◽  
Ischemia Reperfusion Injury ◽  
Therapeutic Potential ◽  
Ischemia Reperfusion ◽  
Antioxidant Properties ◽  
Preservation Solution ◽  
Kidney Preservation ◽  
Preservation Solutions ◽  
Metabolic Reduction

Selenium has strong antioxidant properties and diverse effects on the immune system. The aim of the study was to analyse the protective effect of selenium as a component of a kidney preservation solution on the prevention of ischemia-reperfusion injury of nephrons. The solution was modified by the addition of Se (1 µg/L), prolactin (0.1 µg/L) and Se with prolactin (1 µg/L Se + 0.1 µg/L PRL). The study used a model for storing isolated porcine kidneys in Biolasol® (modified Biolasol®), which minimizes ischemia-reperfusion injury of grafts. The introduction of Se4+ ions at a dose of 1 µg/L into the Biolasol® preservation solution in the form of Na2SeO3 caused an increase in the activity/concentration of the analysed biochemical parameters: aspartate transaminase, alanine transaminase, urea and protein. This suggests an adverse effect of Se4+ on nephron function during ischemia-reperfusion. The best graft protection was obtained by using Biolasol® modified with the addition of selenium (IV) at a dose of 1 µg/L and prolactin at a concentration of 0.1 µg/L. We proposed the mechanism of prolactin action in the metabolic reduction of selenite (SO32−) during ischemia/reperfusion.

scholarly journals The mechanism of action of metabolic cytoprotector trimetazidine in acute ischemia-reperfusion injury

2014 ◽  
Vol 5 (2) ◽  
pp. 24-30
Author(s):  
M. G Glezer ◽  
E. I Astashkin ◽  
M. V Novikova
Keyword(s):  
Reperfusion Injury ◽  
Mechanism Of Action ◽  
Stress Reduction ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Myocardial Damage ◽  
Acute Ischemia ◽  
Positive Effects ◽  
Coronary Syndrome ◽  
New Concepts

The review presents, as the classical data on the mechanism of action of metabolic cytoprotector trimetazidine in acute ischemia/reperfusion injury associated with a partial inhibition of the oxidation of long chain fatty acids and increased metabolism of pyruvate, as well as new concepts of reducing the level of oxidative stress, reduction of cardiomyocyte apoptosis, elimination areas of myocardial stunning and hibernation state. Described cytoprotective effects associated with inhibition of activation of mitochondrial pore with transient (temporary) permeability. Presented clinical studies showing significant anti-anginal and anti-ischemic effect of the trimetazidine in patients with stable angina, to decrease myocardial damage in acute coronary syndrome, during intervention on the coronary arteries. Particular attention is given to the latest data on the positive effects of prolonged use of trimetazidine on the course and prognosis in patients with heart failure.

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