Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association · 2010
Donor pre-treatment with everolimus or cyclosporine does not reduce ischaemia-reperfusion injury in a rat kidney transplant model.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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Martinez-Palli Graciela, Hirose Ryutaro, Liu Tao, Xu Fengyun, Dang Kim, Feiner John, Serkova Natalie J, Niemann Claus U
Аннотация
BACKGROUND: Immunosuppressive agents have been investigated in renal ischaemia-reperfusion injury (IRI) and have frequently demonstrated a beneficial effect. Most studies focused on treatment of the recipient at the time of transplantation. Pre-treatment of these organs before injury (pharmacological pre-conditioning) may particularly protect these organs. This study aimed to investigate the possible protective effects of donor pre-treatment with cyclosporine (CsA) or the mTOR inhibitor everolimus or their combination against IRI during renal transplantation in a rat model.
METHODS: Donors received vehicle, CsA (5 mg/kg), everolimus (0.5 mg/kg) or CsA + everolimus. Two oral doses were administered to the donors at 24 h and again at 6 h prior to donor kidney removal. Syngeneic rat kidneys were preserved in UW solution for 24 h prior to transplantation. After 24 h of reperfusion, blood and tissue samples were collected from recipients for further analysis.
RESULTS: Renal functions as determined by creatinine and necrosis scores were not different between the experimental groups. Cleaved caspase-3, heat shock protein 70 (HSP70), tumor-necrosis factor-alpha (TNF-α) and nitrotyrosine protein levels were not statistically different between the four treatment groups at 24 h post-transplantation. Blood NMR analysis on metabolic markers for IRI reveals no beneficial effects of donor pre-treatment on the 24-h outcome in transplantation.
CONCLUSIONS: When given alone or as a combination to donors before organ recovery, cyclosporine or everolimus does not appear to ameliorate IRI.
METHODS: Donors received vehicle, CsA (5 mg/kg), everolimus (0.5 mg/kg) or CsA + everolimus. Two oral doses were administered to the donors at 24 h and again at 6 h prior to donor kidney removal. Syngeneic rat kidneys were preserved in UW solution for 24 h prior to transplantation. After 24 h of reperfusion, blood and tissue samples were collected from recipients for further analysis.
RESULTS: Renal functions as determined by creatinine and necrosis scores were not different between the experimental groups. Cleaved caspase-3, heat shock protein 70 (HSP70), tumor-necrosis factor-alpha (TNF-α) and nitrotyrosine protein levels were not statistically different between the four treatment groups at 24 h post-transplantation. Blood NMR analysis on metabolic markers for IRI reveals no beneficial effects of donor pre-treatment on the 24-h outcome in transplantation.
CONCLUSIONS: When given alone or as a combination to donors before organ recovery, cyclosporine or everolimus does not appear to ameliorate IRI.