Within a collaborative project of 14 transplant centers, prospective recipients of cadaver kidney grafts were randomized to receive either three pretransplant transfusions or transplants without transfusions. RESULTS; The graft survival rate was significantly higher in the 205 transfusion recipients than in the 218 patients who did not receive transfusions (at 1 year: 90+/-2% vs. 82+/-3%, P=0.020; at 5 years: 79+/-3% vs. 70+/-4%, P=0.025). Cox regression analysis showed that this effect was independent of age, gender, underlying disease, prophylaxis with antilymphocyte antibodies, and preformed lymphocytotoxins. CONCLUSIONS; Transfusion pretreatment improves the outcome of cadaver kidney transplants even with the use of modern immunosuppressive regimens.

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The involvement of the interleukin-4 (IL-4) pathway in B-lymphocyte activation and induction of a T helper 2 (Th2) cell response prompted us to investigate the influence of a recently described gain-of function mutation in the IL-4 receptor alpha-chain gene (IL-4R alpha; CD 124) on renal allograft survival. We developed a genotyping assay for the IL-4R alpha variant Q576R and investigated 203 renal transplant patients, all of whom underwent transplantation surgery at a single institution. The overall frequency of the IL-4R alpha variant Q576R in this group was 38.9% (79/203). The Kaplan-Meier method was used to estimate the graft survival of 156 patients with complete follow-up time of 24 months. Significantly higher graft survival rates (P=0.012, log-rank test) were found in patients with the wild-type IL-4 receptor (2-year graft survival 78.8%) as compared to patients with the IL-4R alpha variant Q576R (2-year graft survival 60.6%). Multifactorial cox regression analysis showed that this effect was independent of HLA matching, sex of donor and recipient, age of recipient, year of transplantation and preformed antibodies (P=0.017). These results indicate a strong association of the IL-4R alpha variant Q576R with kidney allograft loss. Genotyping of kidney allograft recipients for the IL-4R alpha variant may offer a simple method to identify high-risk patients in the post-transplantation period.

While the relevance of pre-formed anti-human leukocyte antigen (HLA) antibodies has been studied extensively, the role of anti-HLA class I and II antibodies produced after cadaveric kidney transplantation is still a matter of discussion. As it has been proposed that they are involved in a considerable number of cases, it should be investigated whether a post-transplant monitoring is a sensitive parameter for the early diagnosis of acute rejection episodes. Additionally, it has been suggested that antibodies are a major cause for chronic rejection; thus, it would be of interest to correlate antibody detection and graft survival. We retrospectively investigated 59 patients after a first cadaveric kidney transplantation without known anti-HLA antibodies (complement-dependent cytotoxicity [CDC] testing). The panel reactivity was determined with a new highly sensitive and specific flow-cytometric technique (Flow-PRA Screening Test, One Lambda, Canoga Park, USA) in sequentially collected serum samples pre- and post-transplant. In patients with acute rejection episodes during the clinical course, the last sample prior to rejection, and in patients without rejection, the last sample prior to discharge, was analyzed. Furthermore, we analyzed 3-yr graft survival and several clinical parameters such as cold ischemia time (CIT). Twenty-four of 59 patients (41%) experienced acute rejections during the clinical course. Five of 59 died with a functioning graft within the first 3 yr. Seven of 54 patients, still alive after 3 yr, lost their graft. Anti-HLA antibodies were detectable in only 7/59 patients and a correlation between antibody positivity and acute rejections (p = 0.32 and 0.54 for anti-HLA class I and II, respectively) could not be identified (sensitivity 12.5 and 8.3%). However, we found a significant correlation between the detection of anti-HLA class II and graft loss within 3 yr (p = 0.005, specificity 97.9%). Additionally, anti-HLA class II positive patients had significantly longer CIT (p = 0.003). Whether the detection of anti-HLA class II antibodies in the early post-transplant phase is of great value for the identification of patients at high risk for early graft loss needs additional investigation. However, we found that anti-HLA antibodies are detectable only in a minority of unsensitized patients and we conclude that flow-cytometric monitoring with Flow PRA is not a sensitive parameter for the early diagnosis of acute rejection episodes in patients after first cadaveric kidney transplantation.

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