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Int. J. Mol. Sci. 2018, 19(2), 454; https://doi.org/10.3390/ijms19020454

The Optimal PEG for Kidney Preservation: A Preclinical Porcine Study

1
Inserm, U1082, 86000 Poitiers, France
2
Faculté de Medecine et Pharmacie, Université de Poitiers, 86000 Poitiers, France
3
CHU de Poitiers, Service de Biochimie, 86000 Poitiers, France
4
FHU SUPORT, 86000 Poitiers, France
5
Faculté de Medecine, Université Claude Bernard Lyon 1, 69622 Villeurbanne, France
6
Réseau CENTAURE, 92160 Antony, France
7
Service d’Urologie et Transplantation, Groupe Hospitalier Pitié Salpetriere, AP-HP, 75013 Paris, France
8
Faculté de Medecine, Université Pierre et Marie Curie, Paris VI, 75005 Paris, France
9
Plate-forme MOPICT-IBiSA, INRA, Unité de Transplantation Expérimentale, GEPA, Domaine du Magneraud, 17700 Surgères, France
10
INSERM U1082, CHU de Poitiers, 2 rue de la Miletrie CS 90577, 86021 Poitiers, France
*
Author to whom correspondence should be addressed.
Received: 30 November 2017 / Revised: 26 December 2017 / Accepted: 29 January 2018 / Published: 3 February 2018
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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). View Full-Text
Keywords: graft preservation; ischemia reperfusion injury; kidney transplantation; PEG; polyethylene glycol graft preservation; ischemia reperfusion injury; kidney transplantation; PEG; polyethylene glycol
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Giraud, S.; Thuillier, R.; Codas, R.; Manguy, E.; Barrou, B.; Valagier, A.; Puichaud, A.; Badet, L.; Nicolas, E.; Eugene, M.; Hauet, T. The Optimal PEG for Kidney Preservation: A Preclinical Porcine Study. Int. J. Mol. Sci. 2018, 19, 454.

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