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

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 WillemsLisa A Robinson, Markus Selzner

Chemistry

Research output: Contribution to journal › Article › peer-review

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.

Original language	English
Article number	e751
Journal	Transplantation direct
Volume	7
Issue number	10
DOIs	https://doi.org/10.1097/TXD.0000000000001218
Publication status	Published - 7 Sep 2021

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Mazilescu, L. I., Urbanellis, P., Kaths, M. J., Ganesh, S., Goto, T., Noguchi, Y., John, R., Konvalinka, A., Mucsi, I., Ghanekar, A., Bagli, D. J., Turgeon, J., Karakeusian Rimbaud, A., Hébert, M-J., Dieudé, M., Alleys, I., Dore, E., Boilard, E., Overkleeft, H. S., ... Selzner, M. (2021). Prolonged Normothermic Ex Vivo Kidney Perfusion Is Superior to Cold Nonoxygenated and Oxygenated Machine Perfusion for the Preservation of DCD Porcine Kidney Grafts. Transplantation direct, 7(10), [e751]. https://doi.org/10.1097/TXD.0000000000001218

@article{2cec0954a7b54d4db220b60f1baec552,

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

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.",

author = "Mazilescu, {Laura I} and Peter Urbanellis and Kaths, {Moritz J} and Sujani Ganesh and Toru Goto and Yuki Noguchi and Rohan John and Ana Konvalinka and Istvan Mucsi and Anand Ghanekar and Bagli, {Darius J} and Julie Turgeon and {Karakeusian Rimbaud}, Annie and Marie-Jos{\'e}e H{\'e}bert and M{\'e}lanie Dieud{\'e} and Isabelle Alleys and Etienne Dore and Eric Boilard and Overkleeft, {Herman S} and Willems, {Lianne I} and Robinson, {Lisa A} and Markus Selzner",

note = "Copyright {\textcopyright} 2021 The Author(s). Transplantation Direct. Published by Wolters Kluwer Health, Inc.",

year = "2021",

month = sep,

day = "7",

doi = "10.1097/TXD.0000000000001218",

language = "English",

volume = "7",

journal = "Transplantation direct",

issn = "2373-8731",

publisher = "Wolters Kluwer Health",

number = "10",

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Mazilescu, LI, Urbanellis, P, Kaths, MJ, Ganesh, S, Goto, T, Noguchi, Y, John, R, Konvalinka, A, Mucsi, I, Ghanekar, A, Bagli, DJ, Turgeon, J, Karakeusian Rimbaud, A, Hébert, M-J, Dieudé, M, Alleys, I, Dore, E, Boilard, E, Overkleeft, HS, Willems, LI, Robinson, LA & Selzner, M 2021, 'Prolonged Normothermic Ex Vivo Kidney Perfusion Is Superior to Cold Nonoxygenated and Oxygenated Machine Perfusion for the Preservation of DCD Porcine Kidney Grafts', Transplantation direct, vol. 7, no. 10, e751. https://doi.org/10.1097/TXD.0000000000001218

TY - JOUR

T1 - Prolonged Normothermic Ex Vivo Kidney Perfusion Is Superior to Cold Nonoxygenated and Oxygenated Machine Perfusion for the Preservation of DCD Porcine Kidney Grafts

AU - Mazilescu, Laura I

AU - Urbanellis, Peter

AU - Kaths, Moritz J

AU - Ganesh, Sujani

AU - Goto, Toru

AU - Noguchi, Yuki

AU - John, Rohan

AU - Konvalinka, Ana

AU - Mucsi, Istvan

AU - Ghanekar, Anand

AU - Bagli, Darius J

AU - Turgeon, Julie

AU - Karakeusian Rimbaud, Annie

AU - Hébert, Marie-Josée

AU - Dieudé, Mélanie

AU - Alleys, Isabelle

AU - Dore, Etienne

AU - Boilard, Eric

AU - Overkleeft, Herman S

AU - Willems, Lianne I

AU - Robinson, Lisa A

AU - Selzner, Markus

PY - 2021/9/7

Y1 - 2021/9/7

N2 - 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.

AB - 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.

U2 - 10.1097/TXD.0000000000001218

DO - 10.1097/TXD.0000000000001218

M3 - Article

C2 - 34514106

VL - 7

JO - Transplantation direct

JF - Transplantation direct

SN - 2373-8731

IS - 10

M1 - e751

ER -