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In this large collaborative study, 2,231 transplanted patients with functioning kidneys were tested for HLA antibodies, then examined 2 years later for graft survival. Among 478 patients with antibodies, 15.1% failed in 2 years, compared to 6.8% failure in 1,753 patients without antibodies (P=0.00000002). Cytotoxicity testing correlated better with outcome than flow cytometry or ELISA testing on HLA coated beads, possibly because it detected non-HLA antigens. When the patients were further broken down into those with serum creatinine at the time of testing of 0.5–1.9, 4.4% of antibody patients failed at 2 years, compared to 4.3% of patients without antibodies. This 0.1% difference increased among patients with serum creatinine values of 2.0–2.9 to 17.9%, and among those with 3.0–3.9 to 16.3%. We conclude that HLA antibodies posttransplantation is predictive of subsequent graft failure, and its predictive value can be enhanced among patients with higher serum creatinine values.