Skip to main content

Lund University Publications

LUND UNIVERSITY LIBRARIES

A new principle to attenuate ischemia-reperfusion injury in kidney transplantation

Biglarnia, Ali-Reza LU orcid ; Teramura, Yuji ; Asif, Sana ; Dührkop, Claudia ; Manivel, Vivek Anand ; Manell, Elin ; Hedenqvist, Patricia ; Rydén, Anneli ; Sellberg, Felix and Fromell, Karin , et al. (2025) In American Journal of Transplantation p.1-13
Abstract

Ischemia-reperfusion injury in transplantation remains a significant clinical challenge with regard to both short-term and long-term complications. In this study, we developed a new amphiphilic construct, polyethylene glycol (PEG)-conjugated lipids (PEG-LIPIDs), to be administered ex vivo intra-arterially to procured porcine kidney allografts before reperfusion. The aim was to create a protective cell membrane barrier, preventing the recognition of ligands exposed on renal cells by plasma proteins and cells of the intravascular innate immune system. In vitro cell studies confirmed the safety of PEG-LIPID with no observed toxicity and demonstrated its efficacy in masking ligands on various cell types. The PEG-LIPID was evaluated in 3... (More)

Ischemia-reperfusion injury in transplantation remains a significant clinical challenge with regard to both short-term and long-term complications. In this study, we developed a new amphiphilic construct, polyethylene glycol (PEG)-conjugated lipids (PEG-LIPIDs), to be administered ex vivo intra-arterially to procured porcine kidney allografts before reperfusion. The aim was to create a protective cell membrane barrier, preventing the recognition of ligands exposed on renal cells by plasma proteins and cells of the intravascular innate immune system. In vitro cell studies confirmed the safety of PEG-LIPID with no observed toxicity and demonstrated its efficacy in masking ligands on various cell types. The PEG-LIPID was evaluated in 3 porcine allogeneic transplant models: 1 acute dual en bloc nonsurvival transplant model (duration 6 hours) and 2 survival models with low and high ischemic stress, respectively (duration 96 hours). No immunosuppression was employed. Across all 3 porcine transplant models, PEG-LIPID consistently mitigated ischemia-reperfusion-induced thromboinflammation (complement, coagulation, and kallikrein/kinin activation) and long-term inflammation with a marked reduction in cytokine responses, including lower levels of interleukin 6. The PEG-LIPID-treated kidneys exhibited significantly improved allograft function, reflected in robustly lower creatinine levels. This translational study confirmed that the PIG-LIPID is a strong candidate drug to mitigate ischemia-reperfusion injury in clinical kidney transplantation.

(Less)
Please use this url to cite or link to this publication:
author
; ; ; ; ; ; ; ; and , et al. (More)
; ; ; ; ; ; ; ; ; ; ; ; ; and (Less)
organization
publishing date
type
Contribution to journal
publication status
epub
subject
in
American Journal of Transplantation
pages
1 - 13
publisher
Elsevier
external identifiers
  • pmid:40998688
ISSN
1600-6135
DOI
10.1016/j.ajt.2025.08.024
project
Preklinisk utveckling av en ny ex vivo-behandling av njurallograft i grismodell för att minska ischemi-reperfusionsskada vid njurtransplantation
language
English
LU publication?
yes
additional info
Copyright © 2025 The Author(s). Published by Elsevier Inc. All rights reserved.
id
51e49c7b-dabd-4299-918b-b7640d6239c8
date added to LUP
2025-12-17 14:09:46
date last changed
2025-12-19 02:25:41
@article{51e49c7b-dabd-4299-918b-b7640d6239c8,
  abstract     = {{<p>Ischemia-reperfusion injury in transplantation remains a significant clinical challenge with regard to both short-term and long-term complications. In this study, we developed a new amphiphilic construct, polyethylene glycol (PEG)-conjugated lipids (PEG-LIPIDs), to be administered ex vivo intra-arterially to procured porcine kidney allografts before reperfusion. The aim was to create a protective cell membrane barrier, preventing the recognition of ligands exposed on renal cells by plasma proteins and cells of the intravascular innate immune system. In vitro cell studies confirmed the safety of PEG-LIPID with no observed toxicity and demonstrated its efficacy in masking ligands on various cell types. The PEG-LIPID was evaluated in 3 porcine allogeneic transplant models: 1 acute dual en bloc nonsurvival transplant model (duration 6 hours) and 2 survival models with low and high ischemic stress, respectively (duration 96 hours). No immunosuppression was employed. Across all 3 porcine transplant models, PEG-LIPID consistently mitigated ischemia-reperfusion-induced thromboinflammation (complement, coagulation, and kallikrein/kinin activation) and long-term inflammation with a marked reduction in cytokine responses, including lower levels of interleukin 6. The PEG-LIPID-treated kidneys exhibited significantly improved allograft function, reflected in robustly lower creatinine levels. This translational study confirmed that the PIG-LIPID is a strong candidate drug to mitigate ischemia-reperfusion injury in clinical kidney transplantation.</p>}},
  author       = {{Biglarnia, Ali-Reza and Teramura, Yuji and Asif, Sana and Dührkop, Claudia and Manivel, Vivek Anand and Manell, Elin and Hedenqvist, Patricia and Rydén, Anneli and Sellberg, Felix and Fromell, Karin and Hammer, Sabine and Huber-Lang, Markus and Ekdahl, Kristina N and Jensen-Waern, Marianne and Nilsson, Bo}},
  issn         = {{1600-6135}},
  language     = {{eng}},
  month        = {{09}},
  pages        = {{1--13}},
  publisher    = {{Elsevier}},
  series       = {{American Journal of Transplantation}},
  title        = {{A new principle to attenuate ischemia-reperfusion injury in kidney transplantation}},
  url          = {{http://dx.doi.org/10.1016/j.ajt.2025.08.024}},
  doi          = {{10.1016/j.ajt.2025.08.024}},
  year         = {{2025}},
}