Communication Dans Un Congrès Année : 2009

The story of polyethylene glycol part 2: PEG during cold preservation protects against chronic graft fibrosis

Résumé

Purpose: Ischemia reperfusion injury (IRI) is strongly associated with chronic graft outcome. Several conservation solutions have been created to reduce IRI severity, some including polyethylene glycol (PEG), which brings general homeostasis benefits and provides immunocamouflage. However, PEG influence on chronic graft outcome remains to be determined.
Method: In a Large White pig model of autotransplantation, kidneys were preserved at 4°C for 24h in either UW as a gold standard or SCOT® (Krebs like solution with an extracellular ionic composition) containing either 15 and 20 g/L PEG20kDa as colloid. Kidneys were evaluated 3 month posttransplant.
Results: Use of either dose of PEG in SCOT® solution improved long-term creatinine as well as interstitial fibrosis compared to UW (p<0.05, see Table). Furthermore, 15g/L of PEG allowed for improvement of proteinuria compared to UW or SCOT® 20g/L (p<0.05).
Quantitative PCR analysis demonstrated that 20g/L PEG lowered the expression of innate immunity markers TLR2 and MCP-1, as well as hypoxia marker HIF1α and angiogenic marker VEGF. Protection against hypoxia was confirmed by reduction of HO-1 expression. Lastly, expression of pro-fibrosis TGFβ1 was downregulated.
SCOT® with 15g/L PEG provided broader protection, as downregulations of the same markers was showed, to which was added downregulation of CMH-I formation protein β2-microglobulin, pro-injury marker Notch4, oxidative stress marker HO-2 and stress protein Hsp70.
Conclusions: Combination of 20kDa PEG with SCOT® preservation solution protected kidney grafts against long term lesions. A dose of 15g/L was best able to maintain graft function and integrity, through downregulation of lesional pathways such as inflammation, hypoxia and cellular stress.

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Dates et versions

hal-05099408 , version 1 (05-06-2025)

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  • HAL Id : hal-05099408 , version 1

Citer

Émilie Manguy, Raphaël Thuillier, Thibeau Desurmont, Michel Eugène, Benoît Barrou, et al.. The story of polyethylene glycol part 2: PEG during cold preservation protects against chronic graft fibrosis. 14th ESOT Congress, The European Society Of Transplantation Congress (ESOT), Aug 2009, Paris, France. ⟨hal-05099408⟩
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