IMPROVING KIDNEY PRESERVATION: HEMO2LIFE® SUPPLEMENTATION RESCUES ISCHEMIA REPERFUSION INJURY

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.

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

International Journal of Molecular Sciences ◽

10.3390/ijms21218156 ◽

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.

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Immune Responses in Kidney Preservation and Reperfusion Injury

Journal of Investigative Medicine ◽

10.1136/jim-52-05-30 ◽

2004 ◽

Vol 52 (5) ◽

pp. 310-314 ◽

Cited By ~ 13

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.

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Ex-vivo Kidney Machine Perfusion: Therapeutic Potential

Frontiers in Medicine ◽

10.3389/fmed.2021.808719 ◽

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.

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