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Human leukocyte antigen (HLA) matching has been de-emphasized in the allocation of renal allografts and further discounting is planned in the new United Network of Organ Sharing kidney allocation model. An unforeseen consequence of poorer matching could be increased sensitization for candidates pursuing retransplantation.We examined candidates listed in the United States from 1988 to 2007 from the Scientific Renal Transplant Registry (SRTR) database that were relisted after loss of a primary kidney transplant (n=15,980). The primary outcome was change in panel reactive antibody (PRA) from prior to recipient's initial transplant to the subsequent listing. Absolute change in PRA levels were examined in general linear models and the likelihood of becoming newly sensitized in logistic models.There was no appreciable change in PRA for patients receiving a first 0 HLA-A, -B, -DR, or 0 HLA-A, -B–mismatched kidney transplant; contrariwise, there was a significant increase in PRA by increasing HLA mismatch of the first transplant. Only 10% of patients became sensitized after a 0 HLA-A, -B–mismatched transplant, whereas the proportion rose up to 37% with increasing HLA mismatches. Other factors, notably younger age and African American race, also contributed to a higher PRA at relisting.Although there might be a limited impact of HLA matching on acute rejection and graft survival, many patients might be negatively impacted from poor HLA matching of their first kidney transplant when needing a second transplant. This might be particularly important in patients with a long life expectancy because of the high likelihood of needing a second transplant during their lifetime.