Prolonged Normothermic Ex Vivo Kidney Perfusion Is Superior to Cold Nonoxygenated and Oxygenated Machine Perfusion for the Preservation of DCD Porcine Kidney Grafts

Laura I Mazilescu; Peter Urbanellis; Moritz J Kaths; Sujani Ganesh; Toru Goto; Yuki Noguchi; Rohan John; Ana Konvalinka; Istvan Mucsi; Anand Ghanekar; Darius J Bagli; Julie Turgeon; Annie Karakeusian Rimbaud; Marie-Josée Hébert; Mélanie Dieudé; Isabelle Alleys; Etienne Dore; Eric Boilard; Herman S Overkleeft; Lianne I Willems; Lisa A Robinson; Markus Selzner

doi:10.1097/TXD.0000000000001218

Prolonged Normothermic Ex Vivo Kidney Perfusion Is Superior to Cold Nonoxygenated and Oxygenated Machine Perfusion for the Preservation of DCD Porcine Kidney Grafts

Transplant Direct. 2021 Sep 7;7(10):e751. doi: 10.1097/TXD.0000000000001218. eCollection 2021 Oct.

Authors

Laura I Mazilescu^{1

2

3}, Peter Urbanellis^{1

4

5}, Moritz J Kaths³, Sujani Ganesh¹, Toru Goto¹, Yuki Noguchi¹, Rohan John^{6

7}, Ana Konvalinka^{5

8}, Istvan Mucsi⁸, Anand Ghanekar¹, Darius J Bagli⁹, Julie Turgeon^{4

10}, Annie Karakeusian Rimbaud^{4

10}, Marie-Josée Hébert^{4

10

11}, Mélanie Dieudé^{4

10

11}, Isabelle Alleys¹², Etienne Dore¹², Eric Boilard^{4

12}, Herman S Overkleeft¹³, Lianne I Willems¹⁴, Lisa A Robinson^{2

15}, Markus Selzner¹

Affiliations

¹ Multi-Organ Transplant Program, Division of General Surgery, Toronto General Hospital, University Health Network, University of Toronto, Toronto, ON, Canada.
² Division of Nephrology, The Hospital for Sick Children, Toronto, ON, Canada.
³ Department of General, Visceral, and Transplantation Surgery, University Hospital Essen, University Duisburg-Essen, Essen, Germany.
⁴ Canadian Donation and Transplantation Research Program, Edmonton, AB, Canada.
⁵ Institute of Medical Science, University of Toronto, Toronto, ON, Canada.
⁶ Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada.
⁷ Department of Pathology, University Health Network, Toronto, ON, Canada.
⁸ Multi-Organ Transplant Program, Division of Nephrology, Toronto General Hospital, University Health Network, University of Toronto, Toronto, ON, Canada.
⁹ Department of Urology, The Hospital for Sick Children, University of Toronto, Toronto, ON, Canada.
¹⁰ Research Centre, Centre hospitalier de l'Université de Montréal (CRCHUM), Montréal, QC, Canada.
¹¹ Université de Montréal, Montréal, QC, Canada.
¹² Département de Microbiologie et Immunologie, Centre de Recherche du CHU de Québec, Université Laval, Québec, QC, Canada.
¹³ Department of Bioorganic Synthesis, Leiden University, Leiden, The Netherlands.
¹⁴ Department of Chemistry, The University of York, York, United Kingdom.
¹⁵ Program in Cell Biology, The Hospital for Sick Children Research Institute, Toronto, ON, Canada.

Abstract

The increased usage of marginal grafts has triggered interest in perfused kidney preservation to minimize graft injury. We used a donation after circulatory death (DCD) porcine kidney autotransplantation model to compare 3 of the most frequently used ex vivo kidney perfusion techniques: nonoxygenated hypothermic machine perfusion (non-oxHMP), oxygenated hypothermic machine perfusion (oxHMP), and normothermic ex vivo kidney perfusion (NEVKP).

Methods: Following 30 min of warm ischemia, grafts were retrieved and preserved with either 16 h of non-oxHMP, oxHMP, or NEVKP (n = 5 per group). After contralateral nephrectomy, grafts were autotransplanted and animals were followed for 8 d. Kidney function and injury markers were compared between groups.

Results: NEVKP demonstrated a significant reduction in preservation injury compared with either cold preservation method. Grafts preserved by NEVKP showed superior function with lower peak serum creatinine (NEVKP versus non-oxHMP versus oxHMP: 3.66 ± 1.33 mg/dL, 8.82 ± 3.17 mg/dL, and 9.02 ± 5.5 mg/dL) and more rapid recovery. The NEVKP group demonstrated significantly increased creatinine clearance on postoperative day 3 compared with the cold perfused groups. Tubular injury scores on postoperative day 8 were similar in all groups.

Conclusions: Addition of oxygen during HMP did not reduce preservation injury of DCD kidney grafts. Grafts preserved with prolonged NEVKP demonstrated superior initial graft function compared with grafts preserved with non-oxHMP or oxHMP in a model of pig DCD kidney transplantation.