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 Effects of Custodiol-N, a novel organ preservation solution, on ischemia/reperfusion injury

2010 ◽  
Vol 139 (4) ◽  
pp. 1048-1056 ◽  
Author(s):  
Sivakkanan Loganathan ◽  
Tamás Radovits ◽  
Kristóf Hirschberg ◽  
Sevil Korkmaz ◽  
Achim Koch ◽  
...  
Keyword(s):  
Reperfusion Injury ◽  
Organ Preservation ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Preservation Solution ◽  
Organ Preservation Solution

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 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.

Loss of clusterin expression worsens renal ischemia-reperfusion injury

2010 ◽  
Vol 298 (3) ◽  
pp. F568-F578 ◽  
Author(s):  
Wenjun Zhou ◽  
Qiunong Guan ◽  
Chris C. H. Kwan ◽  
Huifang Chen ◽  
Martin E. Gleave ◽  
...  
Keyword(s):  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Clinical Care ◽  
Kidney Injury ◽  
Protective Role ◽  
Experimental Models ◽  
Novel Therapy ◽  
Clusterin Expression

Prevention of ischemia-reperfusion injury (IRI) is a challenge in clinical care of the patients with kidney transplants or acute kidney injury, and understanding of the intrinsic mechanisms of resistance to injury in the kidney will lead to a novel therapy. Clusterin, a secreted glycoprotein, is an antiapoptotic protein in cancer cells. Our study is to investigate the role of clusterin in renal IRI. Renal IRI in mice was induced by clamping renal vein and artery for 45 or 50 min at 32°C. Apoptosis of renal tubular epithelial cells (TECs) was determined by FACS analysis. Clusterin expression was examined by Western blot or immunohistochemistry. Here, we showed that clusterin protein was induced in TECs following IRI, and more tubules expressed clusterin in the kidneys following ischemia at higher temperatures. In human proximal TEC HKC-8 cultures, clusterin was upregulated by removal of serum and growth factors in medium and was downregulated by TNF-α-IFN-γ mixture. The levels of clusterin were positively correlated with cell survival in these conditions. Knockdown or knockout of clusterin expression enhanced the sensitivity of TECs to apoptosis. In experimental models of renal IRI, deficiency in clusterin expression worsened the injury, as indicated by a significant increase in renal tissue damage with higher levels of serum creatinine and blood urea nitrogen and by a poorer recovery from the injury in clusterin-deficient mice compared with wild-type mice. Our data indicate that the reduction of inducible expression of clusterin results in an increase in TEC apoptosis in the cultures and renders mice susceptibility to IRI, implying a protective role of clusterin in kidney injury.

Poly(ADP-ribose) polymerase and renal hypothermic preservation injury

2004 ◽  
Vol 286 (5) ◽  
pp. F838-F847 ◽  
Author(s):  
Martin J. Mangino ◽  
Mary Ametani ◽  
Csaba Szabó ◽  
James H. Southard
Keyword(s):  
Enzyme Activity ◽  
Reperfusion Injury ◽  
Cold Storage ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Synthesis Rate ◽  
Renal Tubules ◽  
Hypothermic Preservation ◽  
Preservation Injury ◽  
Parp Activity

The nuclear enzyme poly(ADP-ribose) polymerase (PARP) has been implicated in ischemia-reperfusion injury in many tissues under normothermic conditions. The purpose of this study was to determine whether PARP contributes to mechanisms of the hypothermic ischemia-reperfusion injury that occurs when kidneys are cold stored for transplantation. Cortical tissue slice PARP enzyme activity rose significantly with prolonged cold storage and was dependent on both reperfusion and preservation quality. However, prior exposure to warm ischemia abrogated this increase. PARP protein increased with cold storage but was not dependent on reperfusion. PARP enzyme activity rose quickly after reperfusion in buffer and was not different when whole blood was used. Addition of exogenous hydrogen peroxide (3 mM) to normal renal slices significantly increased PARP activity over 4 h in the cortex but not in the medulla, but the medullary basal PARP synthesis rate was five times higher than that in the cortex. However, the reactive oxygen species (ROS) inhibitors catalase (2,000 U/ml), Trolox (200 μM), and DMSO (15 mM) did not reduce reperfusion-induced PARP activity in cold-stored cortical slices. Finally, PARP inhibitors potentiated preservation injury in isolated canine proximal renal tubules. In conclusion, canine renal PARP enzyme activity rises with prolonged cold storage after reperfusion and may play a protective rather than an injurious role in hypothermic preservation for transplantation. ROS are sufficient but not necessary to activate PARP under these conditions.

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