title: Protective roles of polyethylene glycol and trimetazidine against cold ischemia and reperfusion injuries of pig kidney graft.
abstract: Ischemia-reperfusion injury (IRI) represents an allo-independent risk factor which favors chronic allograft nephropathy (CAN). Here we analyzed the influence of preservation solutions on the function of autotransplanted pig kidneys over 1-16 weeks after surgery. Kidneys were cold-flushed and cold-stored for 24 or 48 h either in University of Wisconsin (UW), modified-UW Hôpital Edouard Herriot, polyethylene glycol 20 kDa (PEG)-supplemented preservation solutions with low K+ (ECPEG) or high K+ (ICPEG) content. Animals autotransplanted with kidneys cold-stored for 24 h in ECPEG exhibited the greatest levels of creatinine clearance (Ccr: 161 +/- 12 mL/min, n=10) and the lowest levels of proteinuria (0.5 +/- 0.03 mg/mL) 16 weeks after surgery as compared with pigs autotransplanted with kidneys cold-stored in the other solutions tested (Ccr ranging from 80 and 140 mL/min). Similar differences, but with lower Ccr levels, were achieved after a prolonged period of cold-storage(48 h). ECPEG better preserved the kidneys from monocytes/macrophages and CD4+ T cells infiltrations, VCAM-1 and MHC class II overexpressions and occurrence of renal interstitial fibrosis (2%) as compared with the other preservation solutions (5%-20%). Adding the anti-ischemic drug trimetazidine (TMZ) to the preservation solutions, particularly ECPEG, further improved the quality of the week-16 post-transplanted kidneys (Ccr: 182 +/- 12 mL/min, n=10). These findings demonstrated that adding PEG to extracellular-like (with low K+ content) preservation solutions in combination with TMZ significantly improved the long-term outcome of kidney grafts in this model of autotransplanted pig kidney.
authors.affiliation: Institut National de la Santéet de la Recherche Médicale (INSERM) ERM 324, rue de La Milétrie, 86000 Poitiers, France.
authors.forename: Jean Pierre
authors.initials: JP
authors.lastname: Faure
authors.forename: Isabelle
authors.initials: I
authors.lastname: Petit
authors.forename: Keqiang
authors.initials: K
authors.lastname: Zhang
authors.forename: Delphine
authors.initials: D
authors.lastname: Dutheil
authors.forename: Carole
authors.initials: C
authors.lastname: Doucet
authors.forename: Frédéric
authors.initials: F
authors.lastname: Favreau
authors.forename: Michel
authors.initials: M
authors.lastname: Eugène
authors.forename: Jean Michel
authors.initials: JM
authors.lastname: Goujon
authors.forename: Jean Paul
authors.initials: JP
authors.lastname: Tillement
authors.forename: Gérard
authors.initials: G
authors.lastname: Mauco
authors.forename: Alain
authors.initials: A
authors.lastname: Vandewalle
authors.forename: Thierry
authors.initials: T
authors.lastname: Hauet
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D003080:Cold Temperature; D005355:Fibrosis / Q000378:metabolism; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006085:Graft Survival; D007150:Immunohistochemistry; D007668:Kidney / Q000378:metabolism / Q000473:pathology; D016030:Kidney Transplantation / Q000379:methods*; D009926:Organ Preservation / Q000379:methods; D019188:Organ Preservation Solutions; D011092:Polyethylene Glycols / Q000494:pharmacology*; D011188:Potassium / Q000737:chemistry / Q000378:metabolism; D015427:Reperfusion Injury / Q000517:prevention & control* / Q000628:therapy; D012997:Solvents / Q000494:pharmacology; D013552:Swine; D013601:T-Lymphocytes / Q000378:metabolism; D013997:Time Factors; D014292:Trimetazidine / Q000494:pharmacology*
chemical_list: D019188:Organ Preservation Solutions; D012997:Solvents; D011092:Polyethylene Glycols; D014292:Trimetazidine; D011188:Potassium