Subnormothermic Ex Vivo Porcine Kidney Perfusion Improves Energy Metabolism: Analysis Using 31P Magnetic Resonance Spectroscopic Imaging

Background. The ideal preservation temperature for donation after circulatory death kidney grafts is unknown. We investigated whether subnormothermic (22 °C) ex vivo kidney machine perfusion could improve kidney metabolism and reduce ischemia-reperfusion injury. Methods. To mimic donation after circ...

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Main Authors: Thomas Agius, MS, Julien Songeon, MS, Antoine Klauser, PhD, Florent Allagnat, PhD, Grégoire Longchamp, MD, Raphael Ruttimann, BS, Arnaud Lyon, MD, Julijana Ivaniesevic, PhD, Raphael Meier, MD, PhD, Sébastien Déglise, MD, James F. Markmann, MD, PhD, Korkut Uygun, PhD, Leo Buhler, MD, Christian Toso, MD, PhD, Jean-Marc Corpataux, MD, Francois Lazeyras, PhD, Alban Longchamp, MD, PhD
Format: Article
Language:English
Published: Wolters Kluwer 2022-10-01
Series:Transplantation Direct
Online Access:http://journals.lww.com/transplantationdirect/fulltext/10.1097/TXD.0000000000001354
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author Thomas Agius, MS
Julien Songeon, MS
Antoine Klauser, PhD
Florent Allagnat, PhD
Grégoire Longchamp, MD
Raphael Ruttimann, BS
Arnaud Lyon, MD
Julijana Ivaniesevic, PhD
Raphael Meier, MD, PhD
Sébastien Déglise, MD
James F. Markmann, MD, PhD
Korkut Uygun, PhD
Leo Buhler, MD
Christian Toso, MD, PhD
Jean-Marc Corpataux, MD
Francois Lazeyras, PhD
Alban Longchamp, MD, PhD
author_facet Thomas Agius, MS
Julien Songeon, MS
Antoine Klauser, PhD
Florent Allagnat, PhD
Grégoire Longchamp, MD
Raphael Ruttimann, BS
Arnaud Lyon, MD
Julijana Ivaniesevic, PhD
Raphael Meier, MD, PhD
Sébastien Déglise, MD
James F. Markmann, MD, PhD
Korkut Uygun, PhD
Leo Buhler, MD
Christian Toso, MD, PhD
Jean-Marc Corpataux, MD
Francois Lazeyras, PhD
Alban Longchamp, MD, PhD
author_sort Thomas Agius, MS
collection DOAJ
description Background. The ideal preservation temperature for donation after circulatory death kidney grafts is unknown. We investigated whether subnormothermic (22 °C) ex vivo kidney machine perfusion could improve kidney metabolism and reduce ischemia-reperfusion injury. Methods. To mimic donation after circulatory death procurement, kidneys from 45-kg pigs underwent 60 min of warm ischemia. Kidneys were then perfused ex vivo for 4 h with Belzer machine perfusion solution UW at 22 °C or at 4 °C before transplantation. Magnetic resonance spectroscopic imaging coupled with LCModel fitting was used to assess energy metabolites. Kidney perfusion was evaluated with dynamic-contrast enhanced MRI. Renal biopsies were collected at various time points for histopathologic analysis. Results. Total adenosine triphosphate content was 4 times higher during ex vivo perfusion at 22 °C than at 4 °C perfusion. At 22 °C, adenosine triphosphate levels increased during the first hours of perfusion but declined afterward. Similarly, phosphomonoesters, containing adenosine monophosphate, were increased at 22 °C and then slowly consumed over time. Compared with 4 °C, ex vivo perfusion at 22 °C improved cortical and medullary perfusion. Finally, kidney perfusion at 22 °C reduced histological lesions after transplantation (injury score: 22 °C: 10.5 ± 3.5; 4 °C: 18 ± 2.25 over 30). Conclusions. Ex vivo kidney perfusion at 22°C improved graft metabolism and protected from ischemia-reperfusion injuries upon transplantation. Future clinical studies will need to define the benefits of subnormothermic perfusion in improving kidney graft function and patient’s survival.
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spelling doaj.art-9276f252910e4f959f46c683d1fc53c62022-12-22T03:22:37ZengWolters KluwerTransplantation Direct2373-87312022-10-01810e135410.1097/TXD.0000000000001354202210000-00014Subnormothermic Ex Vivo Porcine Kidney Perfusion Improves Energy Metabolism: Analysis Using 31P Magnetic Resonance Spectroscopic ImagingThomas Agius, MS0Julien Songeon, MS1Antoine Klauser, PhD2Florent Allagnat, PhD3Grégoire Longchamp, MD4Raphael Ruttimann, BS5Arnaud Lyon, MD6Julijana Ivaniesevic, PhD7Raphael Meier, MD, PhD8Sébastien Déglise, MD9James F. Markmann, MD, PhD10Korkut Uygun, PhD11Leo Buhler, MD12Christian Toso, MD, PhD13Jean-Marc Corpataux, MD14Francois Lazeyras, PhD15Alban Longchamp, MD, PhD161 Department of Vascular Surgery, Centre Hospitalier Universitaire VauDois and University of Lausanne, Lausanne, Switzerland.2 Department of Radiology and Medical Informatics, University of Geneva, Geneva, Switzerland.2 Department of Radiology and Medical Informatics, University of Geneva, Geneva, Switzerland.1 Department of Vascular Surgery, Centre Hospitalier Universitaire VauDois and University of Lausanne, Lausanne, Switzerland.4 Visceral and Transplant Surgery, Department of Surgery, Geneva University Hospitals and Medical School, Geneva, Switzerland.4 Visceral and Transplant Surgery, Department of Surgery, Geneva University Hospitals and Medical School, Geneva, Switzerland.1 Department of Vascular Surgery, Centre Hospitalier Universitaire VauDois and University of Lausanne, Lausanne, Switzerland.5 Metabolomics Platform, Faculty of Biology and Medicine, University of Lausanne, Switzerland.6 Department of Surgery, University of Maryland School of Medicine, Baltimore, MD, USA.1 Department of Vascular Surgery, Centre Hospitalier Universitaire VauDois and University of Lausanne, Lausanne, Switzerland.7 Department of Surgery, Transplant Center, Massachusetts General Hospital, Harvard Medical School, Boston, USA.8 Department of Surgery, Center for Engineering in Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, USA.9 Faculty of Science and Medicine, Section of Medicine, University of Fribourg, Fribourg, Switzerland.4 Visceral and Transplant Surgery, Department of Surgery, Geneva University Hospitals and Medical School, Geneva, Switzerland.1 Department of Vascular Surgery, Centre Hospitalier Universitaire VauDois and University of Lausanne, Lausanne, Switzerland.2 Department of Radiology and Medical Informatics, University of Geneva, Geneva, Switzerland.1 Department of Vascular Surgery, Centre Hospitalier Universitaire VauDois and University of Lausanne, Lausanne, Switzerland.Background. The ideal preservation temperature for donation after circulatory death kidney grafts is unknown. We investigated whether subnormothermic (22 °C) ex vivo kidney machine perfusion could improve kidney metabolism and reduce ischemia-reperfusion injury. Methods. To mimic donation after circulatory death procurement, kidneys from 45-kg pigs underwent 60 min of warm ischemia. Kidneys were then perfused ex vivo for 4 h with Belzer machine perfusion solution UW at 22 °C or at 4 °C before transplantation. Magnetic resonance spectroscopic imaging coupled with LCModel fitting was used to assess energy metabolites. Kidney perfusion was evaluated with dynamic-contrast enhanced MRI. Renal biopsies were collected at various time points for histopathologic analysis. Results. Total adenosine triphosphate content was 4 times higher during ex vivo perfusion at 22 °C than at 4 °C perfusion. At 22 °C, adenosine triphosphate levels increased during the first hours of perfusion but declined afterward. Similarly, phosphomonoesters, containing adenosine monophosphate, were increased at 22 °C and then slowly consumed over time. Compared with 4 °C, ex vivo perfusion at 22 °C improved cortical and medullary perfusion. Finally, kidney perfusion at 22 °C reduced histological lesions after transplantation (injury score: 22 °C: 10.5 ± 3.5; 4 °C: 18 ± 2.25 over 30). Conclusions. Ex vivo kidney perfusion at 22°C improved graft metabolism and protected from ischemia-reperfusion injuries upon transplantation. Future clinical studies will need to define the benefits of subnormothermic perfusion in improving kidney graft function and patient’s survival.http://journals.lww.com/transplantationdirect/fulltext/10.1097/TXD.0000000000001354
spellingShingle Thomas Agius, MS
Julien Songeon, MS
Antoine Klauser, PhD
Florent Allagnat, PhD
Grégoire Longchamp, MD
Raphael Ruttimann, BS
Arnaud Lyon, MD
Julijana Ivaniesevic, PhD
Raphael Meier, MD, PhD
Sébastien Déglise, MD
James F. Markmann, MD, PhD
Korkut Uygun, PhD
Leo Buhler, MD
Christian Toso, MD, PhD
Jean-Marc Corpataux, MD
Francois Lazeyras, PhD
Alban Longchamp, MD, PhD
Subnormothermic Ex Vivo Porcine Kidney Perfusion Improves Energy Metabolism: Analysis Using 31P Magnetic Resonance Spectroscopic Imaging
Transplantation Direct
title Subnormothermic Ex Vivo Porcine Kidney Perfusion Improves Energy Metabolism: Analysis Using 31P Magnetic Resonance Spectroscopic Imaging
title_full Subnormothermic Ex Vivo Porcine Kidney Perfusion Improves Energy Metabolism: Analysis Using 31P Magnetic Resonance Spectroscopic Imaging
title_fullStr Subnormothermic Ex Vivo Porcine Kidney Perfusion Improves Energy Metabolism: Analysis Using 31P Magnetic Resonance Spectroscopic Imaging
title_full_unstemmed Subnormothermic Ex Vivo Porcine Kidney Perfusion Improves Energy Metabolism: Analysis Using 31P Magnetic Resonance Spectroscopic Imaging
title_short Subnormothermic Ex Vivo Porcine Kidney Perfusion Improves Energy Metabolism: Analysis Using 31P Magnetic Resonance Spectroscopic Imaging
title_sort subnormothermic ex vivo porcine kidney perfusion improves energy metabolism analysis using 31p magnetic resonance spectroscopic imaging
url http://journals.lww.com/transplantationdirect/fulltext/10.1097/TXD.0000000000001354
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