Protective roles of polyethylene glycol and trimetazidine against cold ischemia and reperfusion injuries of pig kidney graft.
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.
Faure
Jean Pierre
JP
Institut National de la Santéet de la Recherche Médicale (INSERM) ERM 324, rue de La Milétrie, 86000 Poitiers, France.
Petit
Isabelle
I
Zhang
Keqiang
K
Dutheil
Delphine
D
Doucet
Carole
C
Favreau
Frédéric
F
Eugène
Michel
M
Goujon
Jean Michel
JM
Tillement
Jean Paul
JP
Mauco
Gérard
G
Vandewalle
Alain
A
Hauet
Thierry
T
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*
D019188:Organ Preservation Solutions; D012997:Solvents; D011092:Polyethylene Glycols; D014292:Trimetazidine; D011188:Potassium