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Hypothermic Oxygenated Perfusion: A Simple and Effective Method to Modulate the Immune Response in Kidney Transplantation


Kron, Philipp; Schlegel, Andrea; Muller, Xavier; Gaspert, Ariana; Clavien, Pierre-Alain; Dutkowski, Philipp (2019). Hypothermic Oxygenated Perfusion: A Simple and Effective Method to Modulate the Immune Response in Kidney Transplantation. Transplantation, 103(5):e128-e136.

Abstract

BACKGROUND

Hypothermic oxygenated perfusion (HOPE) has been shown to protect liver recipients from acute rejection in an allogeneic model of liver transplantation in rats. Here we investigate the impact of HOPE on the T cell-mediated immune response following kidney transplantation.

METHODS

Kidneys from Lewis rats were transplanted into Brown Norway recipients to trigger acute rejection (allogeneic untreated group). Next, Brown Norway recipients were treated either with tacrolimus,= or donor kidneys underwent 1h-HOPE-treatment before implantation without additional immunosuppression in recipients. Syngeneic kidney transplants (Brown Norway to Brown Norway) served as controls. In a second set of experiments, the immune response was assessed in a donation after circulatory death model of kidney transplantation comparing standard cold storage with subsequent HOPE treatment and hypothermic nitrogenated perfusion, where oxygen was replaced during cold perfusion.

RESULTS

Allogeneic kidney transplantation led to death in all untreated recipients within 10 days due to severe acute rejection. In contrast, immune activation was prevented by tacrolimus with significantly improved recipient survival. Similarly, HOPE treatment, without any immunosuppression, protected recipients from acute immune response, as measured by less cytokine release, T-cell, and macrophage activation. Additionally, HOPE-treated kidneys showed better function and less early fibrosis leading to a significantly improved recipient survival, compared with untreated allogeneic controls. Similarly, HOPE treatment protected recipients of extended donation after circulatory death kidneys from immune activation. This effect was lost when deoxygenated perfusate was used.

CONCLUSIONS

In summary, this is the first study demonstrating the beneficial effects of HOPE on the immune response following kidney transplantation in an allogeneic rodent model.

Abstract

BACKGROUND

Hypothermic oxygenated perfusion (HOPE) has been shown to protect liver recipients from acute rejection in an allogeneic model of liver transplantation in rats. Here we investigate the impact of HOPE on the T cell-mediated immune response following kidney transplantation.

METHODS

Kidneys from Lewis rats were transplanted into Brown Norway recipients to trigger acute rejection (allogeneic untreated group). Next, Brown Norway recipients were treated either with tacrolimus,= or donor kidneys underwent 1h-HOPE-treatment before implantation without additional immunosuppression in recipients. Syngeneic kidney transplants (Brown Norway to Brown Norway) served as controls. In a second set of experiments, the immune response was assessed in a donation after circulatory death model of kidney transplantation comparing standard cold storage with subsequent HOPE treatment and hypothermic nitrogenated perfusion, where oxygen was replaced during cold perfusion.

RESULTS

Allogeneic kidney transplantation led to death in all untreated recipients within 10 days due to severe acute rejection. In contrast, immune activation was prevented by tacrolimus with significantly improved recipient survival. Similarly, HOPE treatment, without any immunosuppression, protected recipients from acute immune response, as measured by less cytokine release, T-cell, and macrophage activation. Additionally, HOPE-treated kidneys showed better function and less early fibrosis leading to a significantly improved recipient survival, compared with untreated allogeneic controls. Similarly, HOPE treatment protected recipients of extended donation after circulatory death kidneys from immune activation. This effect was lost when deoxygenated perfusate was used.

CONCLUSIONS

In summary, this is the first study demonstrating the beneficial effects of HOPE on the immune response following kidney transplantation in an allogeneic rodent model.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Institute of Pathology and Molecular Pathology
04 Faculty of Medicine > University Hospital Zurich > Clinic for Visceral and Transplantation Surgery
Dewey Decimal Classification:610 Medicine & health
Language:English
Date:May 2019
Deposited On:25 Jul 2019 11:35
Last Modified:27 Feb 2020 08:28
Publisher:Lippincott Williams & Wilkins
ISSN:0041-1337
OA Status:Closed
Publisher DOI:https://doi.org/10.1097/TP.0000000000002634
PubMed ID:30747849

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