A prospective study of 31 cadaveric renal allograft recipients was performed to determine the significance of pretransplant presensitization undetected by the conventional microlymphocytotoxicity crossmatch. Donor-specific humoral presensitization revealed by the antibody-dependent cell-mediated cytotoxicity assay (ADCC) was associated with a high incidence of early graft rejection. Six-month graft survival was 20% in recipients with positive pretransplant ADCC and 75% in ADCC-negative recipients (P < 0.01). Among recipients highly presensitized to a random panel of HLA antigens, donor-specific humoral presensitization detected by chromium-51-release complement-dependent cytotoxicity (51Cr-CDC) was also highly correlated with accelerated rejection (P < 0.05). Pathologic study of the rejected allografts revealed antibody-mediated rejection vasculitis in all recipients. We conclude that humoral presensitization undetected by current conventional methods plays a cardinal role in early renal graft rejection and is a major factor responsible for low cadaveric renal transplant survival. This study suggests that use of the ADCC and 51Cr-CDC as routine adjunctive crossmatch procedures may contribute to improvement in renal transplant survival rates.
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