The Optimal PEG for Kidney Preservation: A Preclinical Porcine Study

Sebastien Giraud 1, 2, 3 Raphael Thuillier 1, 2, 3, 4 Ricardo Codas 1, 5, 6 Emily Manguy 1 Benoit Barrou 1, 7, 8 Alexandre Valagier 1 Alexis Puichaud 1 Lionel Badet 1, 5, 6 Emmanuelle Nicolas 3 Michel Eugene 1 Thierry Hauet 1, 2, 3, 4, 9
4 FHU SUPORT - Fédération Hospitalo-universitaire SUrvival oPtimization in ORgan Transplantation
CHU Poitiers - Centre hospitalier universitaire de Poitiers , CHU Tours, RESINFIT - Anti-infectieux : supports moléculaires des résistances et innovations thérapeutiques, CHU Limoges, IPPRITT - Ciblage individuel et prévention des risques de traitements immunosupresseurs et de la transplantation, IRTOMIT - Ischémie Reperfusion en Transplantation d’Organes Mécanismes et Innovations Thérapeutiques, Cellules Dendritiques, Immunomodulation et Greffes
Abstract : University of Wisconsin (UW) solution is not optimal for preservation of marginal organs. Polyethylene glycol (PEG) could improve protection. Similarly formulated solutions containing either 15 or 20 g/L PEG 20 kDa or 5, 15 and 30 g/L PEG 35 kDa were tested in vitro on kidney endothelial cells, ex vivo on preserved kidneys, and in vivo in a pig kidney autograft model. In vitro, all PEGs provided superior preservation than UW in terms of cell survival, adenosine triphosphate (ATP) production, and activation of survival pathways. Ex vivo, tissue injury was lower with PEG 20 kDa compared to UW or PEG 35 kDa. In vivo, function recovery was identical between UW and PEG 35 kDa groups, while PEG 20 kDa displayed swifter recovery. At three months, PEG 35 kDa 15 and 30 g/L animals had worse outcomes than UW, while 5 g/L PEG 35 kDa was similar. PEG 20 kDa was superior to both UW and PEG 35 kDa in terms of function and fibrosis development, with low activation of damage pathways. PEG 20 kDa at 15 g/L was superior to 20 g/L. While in vitro models did not discriminate between PEGs, in large animal models of transplantation we showed that PEG 20 kDa offers a higher level of protection than UW and that longer chains such as PEG 35 kDa must be used at low doses, such as found in Institut George Lopez (IGL1, 1g/L).
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International Journal of Molecular Sciences, MDPI, 2018, 19 (2), pp.454. 〈10.3390/ijms19020454〉
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Sebastien Giraud, Raphael Thuillier, Ricardo Codas, Emily Manguy, Benoit Barrou, et al.. The Optimal PEG for Kidney Preservation: A Preclinical Porcine Study. International Journal of Molecular Sciences, MDPI, 2018, 19 (2), pp.454. 〈10.3390/ijms19020454〉. 〈hal-01762477〉

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