Oral Preconditioning of Donors After Brain Death With Calcineurin Inhibitors vs. Inhibitors of Mammalian Target for Rapamycin in Pig Kidney Transplantation

脑死亡后供体在猪肾移植中口服钙调磷酸酶抑制剂与哺乳动物雷帕霉素靶标抑制剂的预处理

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作者:Sepehr Abbasi Dezfouli, Mohammadsadegh Nikdad, Omid Ghamarnejad, Elias Khajeh, Alireza Arefidoust, Sara Mohammadi, Ali Majlesara, Mohammadsadegh Sabagh, Negin Gharabaghi, Modar Kentar, Alexander Younsi, Christoph Eckert, Tanja Poth, Mohammad Golriz, Arianeb Mehrabi, Arash Nickkholgh

Background

The systemic inflammatory cascade triggered in donors after brain death enhances the ischemia-reperfusion injury after organ transplantation. Intravenous steroids are routinely used in the intensive care units for the donor preconditioning. Immunosuppressive medications could be potentially used for this

Conclusion

Oral preconditioning with Cyclosporine or Everolimus is feasible in donation after brain death pig kidney transplantation and reduces the expression of TNF-α. Future studies are needed to further delineate the role of oral donor preconditioning against ischemia-reperfusion injury.

Methods

Six hours after the induction of brain death, German landrace donor pigs (33.2 ± 3.9 kg) were randomly preconditioned with either Cyclosporine (n = 9) or Everolimus (n = 9) administered via nasogastric tube with a repeated dose just before organ procurement. Control donors received intravenous Methylprednisolone (n = 8). Kidneys were procured, cold-stored in Histidine-Tryptophane-Ketoglutarate solution at 4°C and transplanted in nephrectomized recipients after a mean cold ischemia time of 18 h. No post-transplant immunosuppression was given to avoid confounding bias. Blood samples were obtained at 4 h post reperfusion and daily until postoperative day 5 for complete blood count, blood urea nitrogen, creatinine, and electrolytes. Graft protocol biopsies were performed 4 h after reperfusion to assess early histological and immunohistochemical changes.

Results

There was no difference in the hemodynamic parameters, hemoglobin/hematocrit and electrolytes between the groups. Serum blood urea nitrogen and creatinine peaked on postoperative day 1 in all groups and went back to the preoperative levels at the

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