HLA typings and panel reactive antibody determinations were performed in the tissue typing laboratories of participating centers and reported to the study center in Heidelberg for analysis. All pretransplant sera were tested at the study center also for the presence of HLA alloantibodies using the AbScreen I und II ELISA kits of Bio-Rad (Munich, Germany), which use pooled HLA antigens and enable detection of HLA-A, -B, -C, -DR, and -DQ antibodies of the IgG isotype. Based on our previous findings (24, 25), an optical density (OD) of more than or equal to 300 was used as cut-off for positivity. Information on graft function and patient survival was documented at 3 and 6 months and yearly thereafter. Actuarial survival rates were computed according to the Kaplan-Meier method (26) and expressed as % ±standard error. Curves were compared using the log-rank test. For multivariate Cox regression analysis the following confounders were considered: transplant year, transplant number (retransplant), recipient race, recipient gender, donor gender, geographical region, recipient age, donor age, HLA A+B+DR mismatches, highest pretransplant cytotoxic panel reactivity, time on dialysis, original disease, ischemic preservation time, general clinical evaluation of the patient as a candidate for transplantation, and immunosuppressive therapy (type of calcineurin inhibitor, type of antimetabolite, steroids, antibody induction with IL-2 receptor antagonist, antibody induction with antithymocyte globulin). A back step elimination algorithm was used to exclude confounding factors with a threshold of P more than 0.2, and HRs for cumulative 3-year survival after serum date were calculated. Statistical calculations were performed using IBM SPSS Statistics (PASW version 18.0, SPSS Inc., Chicago, IL).
The authors thank Tina Nonn for excellent technical assistance, Andrea Ruhenstroth for assistance with the computer analysis, and staff members at the participating laboratories and clinical units for supplying us with sera and clinical follow-up data.
Sera and data for this multicenter analysis were provided by transplantation centers in the following cities: Baracaldo, Spain (Dr. Maruri, n=31); Bremen, Germany (Dr. Melchior, n=3); Budapest, Hungary (Dr. Langer, n=108); Cagliari, Italy (Dr. Altieri, n=66); Dresden, Germany (Dr. Gross, n=3); Freiburg, Germany (Dr. Pisarski, n=152); Giessen, Germany (Dr. Weimer, n=117); Halle, Germany (Dr. Altermann, n=2); Heidelberg, Germany (Dr. Zeier, n=421); Helsinki, Finland (Dr. Kyllönen, n=148); Innsbruck, Austria (Dr. Bösmüller, n=30); Izmir, Turkey (Dr. Yener, n=13); Leuven, Belgium (Dr. Vanrenterghem, n=314); Mannheim, Germany (Dr. Schnülle, n=1); Medellin, Columbia (Dr. Garcia, n=28); Mexico City, Mexico (Dr. Alberu-Gomez, n=14); Portland, OR (Dr. Norman, n=10); Porto Alegre, Brazil (Dr. Duro-Garcia, n=14); Prague, Czechia (Dr. Slavcev, n=172); Quebec, Canada (Dr. Roy, n=333); Reims, France (Dr. Cohen, n=23); Rijeka, Croatia (Dr. Balen, n=57); Rostock, Germany (Dr. Stein, n=3); Sao Paulo, Brazil (Dr. Medina-Pestana, n=11); St. Etienne, France (Dr. Berthoux, n=22); Torino, Italy (Dr. Amoroso, n=213); Ulm, Germany (Dr. Mytilineos, n=11), Valencia, Spain (Dr. Simon, n=2). We are indebted to the colleagues and staff members at these centers for their invaluable support.
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