MOLECULAR MECHANISMS OF DELAYED KIDNEY GRAFT FUNCTION

J.N. Hoffmann, J.M. Fertmann, W. Illner, H. Arbogast, W. Land, K. Jauch
University Of Munich, Dept. of Surgery - Transplant Surgery, Munich/GERMANY

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Introduction: High-dose antithrombin (AT) can reduce reperfusion injury after human pancreas-kidney transplantation. We evaluated the effect of intraoperative administration of high-dose AT on ischemia/reperfusion (I/R) injury in deceased donor kidney transplantation in a single-center, randomized controlled study. Methods: Consecutive patients undergoing deceased donor kidney transplantation were randomized into two groups. One (AT, n=36) was treated prophylactically with 4,000 IU AT intravenously before graft reperfusion; the second (control, n=34) received standard therapy. To quantify graft perfusion as a parameter of I/R injury, 5 intraoperative and daily postoperative color-coded Doppler ultrasound measurements were performed. The arterio-capsular distance (ACD) served as a measure of graft reperfusion. Safety parameters, graft function and incidence of rejection episodes were monitored prospectively for 12 months. Results: The groups were similar with respect to most demographic and baseline laboratory parameters, although more control group patients were undergoing re-transplantation. AT treatment was effective in restoring postoperatively decreased serum AT activities (p<0.001). Red blood cell transfusion requirement and the incidence of bleeding complications were not affected by AT. In AT patients, ACD was significantly reduced vs. controls intraoperatively (p<0.01) and over 7 postoperative days (p<0.05). Early and long-term (6, 12 month) graft function, incidence of rejection episodes and patient and graft survival were not altered by AT treatment. Conclusion: A single intraoperative dose of AT reduced I/R injury after deceased donor kidney transplantation as demonstrated by significantly improved graft perfusion. AT did not significantly effect early and long-term graft function. Repetitive AT therapy should be tested in a selected patient population on higher risk for delayed graft function.

Disclosure: All authors have declared no conflicts of interest.