Effect of polyethylene glycol-based preservation solutions on graft injury in experimental kidney transplantation

• DOI: 10.1002/bjs.7332
• Publication Date: 2010-11-16T15:12:27Z
• Authors: R Thuillier; C Renard; C Rogel-Gaillard; J Demars; D Milan; L Forestier; A Ouldmoulene; J M Goujon; L Badet; T Hauet
• Keywords: Male; 0301 basic medicine; kidney; CD3 Complex; Swine; [SDV]Life Sciences [q-bio]; Macrophages; Blotting, Western; Graft Survival; Organ Preservation Solutions; 610; Recovery of Function; Fibrosis; Kidney Transplantation; Polyethylene Glycols; 3. Good health; 03 medical and health sciences; Kidney Tubules; Reperfusion Injury; polyethylene glycol; 617; Animals; transplantation

Abstract

Background New preservation solutions are emerging, of various ionic compositions and with hydroxyethyl starch replaced by polymers such as polyethylene glycols (PEGs), offering the potential for ‘immunocamouflage’. This experimental study investigated which of three clinically available preservation protocols offered the best graft protection, based on epithelial-to-mesenchymal transition (EMT) and fibrosis.

Methods Kidneys were preserved for 24 h at 4 °C with University of Wisconsin solution (UW) as standard, compared with solutions containing either 1 g/l PEG 35 kDa (Institute Georges Lopez solution, IGL) or 30g/l PEG 20 kDa (solution de conservation des organes et des tissus, SCOT). Animals were followed for up to 3 months and development of EMT, tubular atrophy and fibrosis was evaluated in comparison with sham-operated animals.

Results Functional recovery was better in the SCOT group compared with the other groups. Chronic fibrosis, EMT and inflammation were observed in the UW and IGL groups, but limited in the SCOT group. Levels of profibrosis markers such as transforming growth factor β1, plasminogen activator inhibitor 1 and connective tissue growth factor were increased in IGL and UW groups compared with the SCOT group. Hypoxia-inducible factor (HIF) 1α and 2α expression was increased at 3 months in grafts preserved in UW and IGL, but detected transiently on day 14 when SCOT was used. Expression of HIF-regulated genes vascular endothelial growth factor and erythropoietin was increased in UW and IGL groups.

Conclusion The choice of colloid and ionic content is paramount in providing long-term protection against chronic graft injury after renal transplantation. Preservation solutions based on PEGs may optimize graft quality.