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- W2335766643 abstract "Introduction: Static organ preservation still needs to be improved for an optimal use of marginal donors. Coagulation activation triggers major injuries affecting organs during the transplantation process and particularly during the ischemic phase. We previously demonstrated the benefit of specific inhibitors of different coagulation enzymes during the graft preservation period to reduce ischemia reperfusion injury (IRI). In the current work, we tested a new compound with a unique anticoagulant profile (EP217609) for its effectiveness in organ preservation. Methods: EP217609 was evaluated in vitro, in endothelial cells (first cells affected by IRI) cultivated under conditions mimicking organ preservation, and in vivo in a porcine model of kidney auto-transplantation. Kidneys were subjected to 60 min warm ischemia prior to collection and preservation during 24 hours in static conditions, using the University of Wisconsin solution (UW) supplemented with standard heparin (UFH) or EP217609. After kidney transplantation, animals were followed for 3 months until sacrifice. Results: In vitro, addition of EP217609 improved cell survival as well as ATP levels. In vivo, kidneys preserved with UW+UFH showed delayed function recovery, with only 50% (3/6) animals recovering function at day 2, compared to 83% (5/6) of animals from the EP217609 group. The 3 months follow up revealed benefits of EP217609 supplementation illustrated by a significantly faster return to physiological creatininemia levels obtained as early as day 30 (p< 0.05 versus UFH). In addition, fibrosis level was importantly reduced in this group in agreement with a better long term graft function. Conclusion: In this model, targeting the coagulation pathway with EP217609 during kidney preservation provided benefits for the graft both on acute and chronic outcomes. The unique anticoagulant profile of EP217609 makes it effective in organ preservation, with a high potential for translation to the clinic. Indeed, such a molecule, easily added to a preservation protocol in the clinic, would be invaluable to help facing the decreasing quality of transplanted organs." @default.
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- W2335766643 date "2012-11-01" @default.
- W2335766643 modified "2023-10-18" @default.
- W2335766643 title "Organ Preservation Revisited: Anticoagulation Improves Early and Long Term Kidney Graft Function" @default.
- W2335766643 doi "https://doi.org/10.1097/00007890-201211271-02276" @default.
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