Effect of polyethylene glycol-based preservation solutions on graft injury in experimental kidney transplantation.
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 30 g/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.


CONCLUSIONS
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.
Institut National de Santé et de Recherche Médicale (INSERM) U927 and Université de Poitiers, Poitiers, France.
R
R
Thuillier
C
C
Renard
C
C
Rogel-Gaillard
J
J
Demars
D
D
Milan
L
L
Forestier
A
A
Ouldmoulene
J M
JM
Goujon
L
L
Badet
T
T
Hauet
D000818:Animals; D015153:Blotting, Western; D017252:CD3 Complex; D005355:Fibrosis; D006085:Graft Survival / Q000187:drug effects; D016030:Kidney Transplantation / Q000379:methods*; D007684:Kidney Tubules / Q000098:blood supply; D008264:Macrophages / Q000473:pathology; D008297:Male; D019188:Organ Preservation Solutions / Q000737:chemistry / Q000627:therapeutic use*; D011092:Polyethylene Glycols / Q000737:chemistry / Q000627:therapeutic use*; D020127:Recovery of Function; D015427:Reperfusion Injury / Q000517:prevention & control*; D013552:Swine
D017252:CD3 Complex; D019188:Organ Preservation Solutions; C071285:hydroxyethyl starch-free University of Wisconsin solution; D011092:Polyethylene Glycols