The Effects of 6-Chromanol SUL-138 during Hypothermic Machine Perfusion on Porcine Deceased Donor Kidneys

Diminishing ischemia-reperfusion injury (IRI) by improving kidney preservation techniques offers great beneficial value for kidney transplant recipients. Mitochondria play an important role in the pathogenesis of IRI and are therefore interesting targets for pharmacological interventions. Hypothermi...

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Main Authors: L. Annick van Furth, Leonie H. Venema, Koen D. W. Hendriks, Pieter C. Vogelaar, Guido Krenning, Henri G. D. Leuvenink
Format: Article
Language:English
Published: MDPI AG 2021-08-01
Series:Transplantology
Subjects:
DCD
Online Access:https://www.mdpi.com/2673-3943/2/3/31
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spelling doaj-04ce744c5cb0468bb334fb3ca7c79ec02021-09-26T01:34:01ZengMDPI AGTransplantology2673-39432021-08-0123130431410.3390/transplantology2030031The Effects of 6-Chromanol SUL-138 during Hypothermic Machine Perfusion on Porcine Deceased Donor KidneysL. Annick van Furth0Leonie H. Venema1Koen D. W. Hendriks2Pieter C. Vogelaar3Guido Krenning4Henri G. D. Leuvenink5Department of Surgery, University Medical Centre Groningen, University of Groningen, 9726 Groningen, The NetherlandsDepartment of Surgery, University Medical Centre Groningen, University of Groningen, 9726 Groningen, The NetherlandsDepartment of Surgery, University Medical Centre Groningen, University of Groningen, 9726 Groningen, The NetherlandsDepartment of Clinical Pharmacy and Pharmacology, University Medical Centre Groningen, University of Groningen, 9726 Groningen, The NetherlandsSulfateq B.V., 9726 Groningen, The NetherlandsDepartment of Surgery, University Medical Centre Groningen, University of Groningen, 9726 Groningen, The NetherlandsDiminishing ischemia-reperfusion injury (IRI) by improving kidney preservation techniques offers great beneficial value for kidney transplant recipients. Mitochondria play an important role in the pathogenesis of IRI and are therefore interesting targets for pharmacological interventions. Hypothermic machine perfusion (HMP), as a preservation strategy, offers the possibility to provide mitochondrial–targeted therapies. This study focuses on the addition of a mitochondrial protective agent SUL—138 during HMP and assesses its effect on kidney function and injury during normothermic reperfusion. In this case, 30 min of warm ischemia was applied to porcine slaughterhouse kidneys before 24 h of non–oxygenated HMP with or without the addition of SUL—138. Functional assessment was performed by 4 h normothermic autologous blood reperfusion. No differences in renal function or perfusion parameters were found between both groups. ATP levels were lower after 30 min of warm ischemia in the SUL–138 group (n.s, <i>p</i> = 0.067) but restored significantly during 24 h of HMP in combination with SUL—138. Aspartate aminotransferase (ASAT) levels were significantly lower for the SUL—138 group. SUL—138 does not influence renal function in this model. Restoration of ATP levels during 24 h of HMP with the addition of SUL in combination with lower ASAT levels could be an indication of improved mitochondrial function.https://www.mdpi.com/2673-3943/2/3/31SUL—138machine perfusionischemia reperfusion injurykidneyDCDmitochondria
collection DOAJ
language English
format Article
sources DOAJ
author L. Annick van Furth
Leonie H. Venema
Koen D. W. Hendriks
Pieter C. Vogelaar
Guido Krenning
Henri G. D. Leuvenink
spellingShingle L. Annick van Furth
Leonie H. Venema
Koen D. W. Hendriks
Pieter C. Vogelaar
Guido Krenning
Henri G. D. Leuvenink
The Effects of 6-Chromanol SUL-138 during Hypothermic Machine Perfusion on Porcine Deceased Donor Kidneys
Transplantology
SUL—138
machine perfusion
ischemia reperfusion injury
kidney
DCD
mitochondria
author_facet L. Annick van Furth
Leonie H. Venema
Koen D. W. Hendriks
Pieter C. Vogelaar
Guido Krenning
Henri G. D. Leuvenink
author_sort L. Annick van Furth
title The Effects of 6-Chromanol SUL-138 during Hypothermic Machine Perfusion on Porcine Deceased Donor Kidneys
title_short The Effects of 6-Chromanol SUL-138 during Hypothermic Machine Perfusion on Porcine Deceased Donor Kidneys
title_full The Effects of 6-Chromanol SUL-138 during Hypothermic Machine Perfusion on Porcine Deceased Donor Kidneys
title_fullStr The Effects of 6-Chromanol SUL-138 during Hypothermic Machine Perfusion on Porcine Deceased Donor Kidneys
title_full_unstemmed The Effects of 6-Chromanol SUL-138 during Hypothermic Machine Perfusion on Porcine Deceased Donor Kidneys
title_sort effects of 6-chromanol sul-138 during hypothermic machine perfusion on porcine deceased donor kidneys
publisher MDPI AG
series Transplantology
issn 2673-3943
publishDate 2021-08-01
description Diminishing ischemia-reperfusion injury (IRI) by improving kidney preservation techniques offers great beneficial value for kidney transplant recipients. Mitochondria play an important role in the pathogenesis of IRI and are therefore interesting targets for pharmacological interventions. Hypothermic machine perfusion (HMP), as a preservation strategy, offers the possibility to provide mitochondrial–targeted therapies. This study focuses on the addition of a mitochondrial protective agent SUL—138 during HMP and assesses its effect on kidney function and injury during normothermic reperfusion. In this case, 30 min of warm ischemia was applied to porcine slaughterhouse kidneys before 24 h of non–oxygenated HMP with or without the addition of SUL—138. Functional assessment was performed by 4 h normothermic autologous blood reperfusion. No differences in renal function or perfusion parameters were found between both groups. ATP levels were lower after 30 min of warm ischemia in the SUL–138 group (n.s, <i>p</i> = 0.067) but restored significantly during 24 h of HMP in combination with SUL—138. Aspartate aminotransferase (ASAT) levels were significantly lower for the SUL—138 group. SUL—138 does not influence renal function in this model. Restoration of ATP levels during 24 h of HMP with the addition of SUL in combination with lower ASAT levels could be an indication of improved mitochondrial function.
topic SUL—138
machine perfusion
ischemia reperfusion injury
kidney
DCD
mitochondria
url https://www.mdpi.com/2673-3943/2/3/31
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