phaidra.vetmeduni.ac.at o:5375 DOI 10.1016/j.ajt.2025.08.024 A new principle to attenuate ischemia-reperfusion injury in kidney transplantation 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. eng Intravascular Innate Immunity Ischemia-reperfusion Injury Kidney Transplantation Pretreatment Modality 2026-07-28T14:08:12.590Z LOMv1.0 Author BEGIN:VCARD VERSION:3.0 N:Biglarnia;Ali-Reza; FN:Ali-Reza Biglarnia X-ORCID:https://orcid.org/0009-0004-2293-0740 END:VCARD BEGIN:VCARD VERSION:3.0 N:Teramura;Yuji; FN:Yuji Teramura X-ORCID:https://orcid.org/0000-0002-0709-1000 END:VCARD BEGIN:VCARD VERSION:3.0 N:Asif;Sana; FN:Sana Asif X-ORCID:https://orcid.org/0000-0001-7924-0936 END:VCARD BEGIN:VCARD VERSION:3.0 N:Dührkop;Claudia; FN:Claudia Dührkop X-ORCID:https://orcid.org/0009-0006-9405-4035 END:VCARD BEGIN:VCARD VERSION:3.0 N:Manivel;Vivek Anand; FN:Vivek Anand Manivel X-ORCID:https://orcid.org/0000-0002-6746-7372 END:VCARD BEGIN:VCARD VERSION:3.0 N:Manell;Elin; FN:Elin Manell X-ORCID:https://orcid.org/0000-0002-4491-7609 END:VCARD BEGIN:VCARD VERSION:3.0 N:Hedenqvist;Patricia; FN:Patricia Hedenqvist X-ORCID:https://orcid.org/0000-0003-4540-6250 END:VCARD BEGIN:VCARD VERSION:3.0 N:Rydén;Anneli; FN:Anneli Rydén X-ORCID:https://orcid.org/0000-0002-3070-5023 END:VCARD BEGIN:VCARD VERSION:3.0 N:Sellberg;Felix; FN:Felix Sellberg X-ORCID:https://orcid.org/0000-0002-9742-244X END:VCARD BEGIN:VCARD VERSION:3.0 N:Fromell;Karin; FN:Karin Fromell X-ORCID:https://orcid.org/0000-0001-8905-8791 END:VCARD BEGIN:VCARD VERSION:3.0 N:Hammer;Sabine; FN:Sabine Hammer X-ORCID:https://orcid.org/0000-0003-1475-3938 END:VCARD BEGIN:VCARD VERSION:3.0 N:Huber-Lang;Markus; FN:Markus Huber-Lang X-ORCID:https://orcid.org/0000-0003-2359-6516 END:VCARD BEGIN:VCARD VERSION:3.0 N:Ekdahl;Kristina N.; FN:Kristina N. Ekdahl X-ORCID:https://orcid.org/0000-0001-7888-1571 END:VCARD BEGIN:VCARD VERSION:3.0 N:Jensen-Waern;Marianne; FN:Marianne Jensen-Waern X-ORCID:https://orcid.org/0000-0001-6195-7066 END:VCARD BEGIN:VCARD VERSION:3.0 N:Nilsson;Bo; FN:Bo Nilsson X-ORCID:https://orcid.org/0000-0003-0057-2730 END:VCARD https://w3id.org/kim/hcrt/scheme https://w3id.org/kim/hcrt/text Textdokument Text LOMv1.0 yes https://creativecommons.org/licenses/by/4.0 application/pdf 4954810 https://phaidra.vetmeduni.ac.at/o:5375 https://phaidra.vetmeduni.ac.at/api/object/o:5375/thumbnail LOMv1.0 discipline