scholarly journals Normothermic Ex Vivo Kidney Perfusion for the Preservation of Kidney Grafts prior to Transplantation

10.3791/52909 ◽  
2015 ◽  
Author(s):  
J. Moritz Kaths ◽  
Vinzent N. Spetzler ◽  
Nicolas Goldaracena ◽  
Juan Echeverri ◽  
Kristine S. Louis ◽  
...  
Keyword(s):  
Ex Vivo ◽  
Kidney Perfusion

scholarly journals Lowering Perfusate Temperature From 37°C to 32°C Diminishes Function in a Porcine Model of Ex Vivo Kidney Perfusion

2017 ◽  
Vol 3 (3) ◽  
pp. e140 ◽  
Author(s):  
Thomas D. Adams ◽  
Meeta Patel ◽  
Sarah A. Hosgood ◽  
Michael L. Nicholson
Keyword(s):  
Porcine Model ◽  
Ex Vivo ◽  
Kidney Perfusion

scholarly journals Normothermic Ex-vivo Kidney Perfusion in a Porcine Auto-Transplantation Model Preserves the Expression of Key Mitochondrial Proteins: An Unbiased Proteomics Analysis

2020 ◽  
Author(s):  
Caitriona M. McEvoy ◽  
Sergi Clotet-Freixas ◽  
Tomas Tokar ◽  
Chiara Pastrello ◽  
Shelby Reid ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Ischemia Reperfusion Injury ◽  
Ex Vivo ◽  
Ischemia Reperfusion ◽  
Graft Function ◽  
Kidney Injury ◽  
Tca Cycle ◽  
Proteomics Analysis ◽  
Beneficial Effects ◽  
Kidney Perfusion

AbstractNormothermic ex-vivo kidney perfusion (NEVKP) results in significantly improved graft function in porcine auto-transplant models of DCD injury compared to static cold storage (SCS); however, the molecular mechanisms underlying these beneficial effects remain unclear. We performed an unbiased proteomics analysis of 28 kidney biopsies obtained at 3 time points from pig kidneys subjected to 30-minutes of warm ischemia, followed by 8 hours of NEVKP or SCS, and auto-transplantation. 70/6593 proteins quantified were differentially expressed between NEVKP and SCS groups (FDR<0.05). Proteins increased in NEVKP mediated key metabolic processes including fatty acid ß-oxidation, the TCA-cycle and oxidative phosphorylation. Comparison of our findings with external datasets of ischemia-reperfusion, and other models of kidney injury confirmed that 47 of our proteins represent a common signature of kidney injury reversed or attenuated by NEVKP. We validated key metabolic proteins (ETFB, CPT2) by immunoblotting. Transcription factor databases identified PPARGC1A, PPARA/G/D and RXRA/B as the upstream regulators of our dataset, and we confirmed their increased expression in NEVKP with RT-PCR. The proteome-level changes observed in NEVKP mediate critical metabolic pathways that may explain the improved graft function observed. These effects may be coordinated by PPAR-family transcription factors, and may represent novel therapeutic targets in ischemia-reperfusion injury.

scholarly journals Normothermic ex vivo kidney perfusion for graft quality assessment prior to transplantation

2017 ◽  
Vol 18 (3) ◽  
pp. 580-589 ◽  
Author(s):  
J. Moritz Kaths ◽  
Mátyás Hamar ◽  
Juan Echeverri ◽  
Ivan Linares ◽  
Peter Urbanellis ◽  
...  
Keyword(s):  
Quality Assessment ◽  
Ex Vivo ◽  
Kidney Perfusion ◽  
Graft Quality

scholarly journals Significant Dysfunction of Kidney Grafts Exposed to Prolonged Warm Ischemia Is Minimized Through Normothermic Ex Vivo Kidney Perfusion

2020 ◽  
Vol 6 (8) ◽  
pp. e587
Author(s):  
Peter Urbanellis ◽  
Dagmar Kollmann ◽  
Ivan Linares ◽  
Sujani Ganesh ◽  
Fabiola Oquendo ◽  
...  
Keyword(s):  
Ex Vivo ◽  
Warm Ischemia ◽  
Kidney Perfusion

scholarly journals Ex vivo analysis of graft viability using 31P magnetic resonance imaging spectroscopy

2021 ◽  
Vol 108 (Supplement_4) ◽  
Author(s):  
A Longchamp ◽  
A Klauser ◽  
T Agius ◽  
J Songeon ◽  
A Nastasi ◽  
...  
Keyword(s):  
Magnetic Resonance Imaging ◽  
Magnetic Resonance ◽  
Ex Vivo ◽  
High Energy ◽  
Warm Ischemia ◽  
Kidney Graft ◽  
Resonance Imaging ◽  
Atp Levels ◽  
Kidney Perfusion ◽  
Circulatory Death

Abstract Objective Expansion in organ supply has been proposed through the use of organs after circulatory death (donation after circulatory death [DCD]) in order to face the chronic shortage of kidneys for transplantation. However, many DCD grafts are discarded because of long warm ischemia times, and the absence of reliable non-invasive means to determine kidney viability. P magnetic resonance imaging (pMRI) spectroscopy is a noninvasive method to detect high-energy phosphate metabolites, such as ATP. However, the reliability of pMRI to predict kidney energy state, and its viability before transplantation remain also unknown. Methods To mimic DCD, pig kidneys underwent 0, 30 min or 60 min of warm ischemia, before oxygenated hypothermic machine perfusion (HMP). During the ex vivo perfusion, we assessed energy metabolites and Gadolinium elimination using pMRI. Each sample underwent histopathological scoring. Results Using pMRI, we found that in pig kidney, ATP was rapidly generated in presence of oxygen (100 kPa), which remained stable up to 22 h. Warm ischemia (60 min) induced significant histological damages, delayed cortical and medullary Gadolinium elimination (perfusion), and reduced ATP levels, but not its precursors (AMP). Finally, ATP levels and kidney perfusion both inversely correlated with the severity of kidney histological injury. Conclusion ATP levels, and kidney perfusion measurements using pMRI, are biomarkers of kidney injury after warm ischemia. Future work will define the role of pMRI in predicting kidney graft viability and patient's survival.

scholarly journals MITOCHONDRIAL METABOLISM IS PRESERVED FOLLOWING NORMOTHERMIC EX-VIVO KIDNEY PERFUSION OF GRAFTS PROCURED FOLLOWING CARDIAC DEATH

2020 ◽  
Vol 104 (S3) ◽  
pp. S249-S249
Author(s):  
Peter Urbanellis ◽  
Caitriona McEvoy ◽  
Marko Skrtic ◽  
Ivan Linares ◽  
Dagmar Kollmann ◽  
...  
Keyword(s):  
Cardiac Death ◽  
Ex Vivo ◽  
Mitochondrial Metabolism ◽  
Kidney Perfusion

Normothermic Ex Vivo Kidney Perfusion Improves Early DCD Graft Function Compared With Hypothermic Machine Perfusion and Static Cold Storage

2020 ◽  
Vol 104 (5) ◽  
pp. 947-955 ◽  
Author(s):  
Peter Urbanellis ◽  
Matyas Hamar ◽  
J. Moritz Kaths ◽  
Dagmar Kollmann ◽  
Ivan Linares ◽  
...  
Keyword(s):  
Cold Storage ◽  
Ex Vivo ◽  
Graft Function ◽  
Machine Perfusion ◽  
Hypothermic Machine Perfusion ◽  
Kidney Perfusion

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.

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