P142 Hyperacute rejection in a kidney transplant recipient with no HLA antibodies

A 65 year old, blood group O, African-American male with 0% CPRA received a blood group O deceased donor kidney transplant with a negative crossmatch (XM). During surgery, the transplanted kidney became dusky within minutes of restoring blood flow. There was no suspicion of anti-HLA or anti-ABO antibodies which could mediate hyperacute rejection, so a thrombotic event or anatomical defect was suspected. The OPO consented to allocate the second kidney from the same donor; it was transplanted within hours, and the same events transpired. Three days later, the recipient had bleeding and pain at the graft site, and donor vein and artery grafts had to be removed. We sought to identify the factors which caused the allografts loss. Both kidneys were sent for microscopic and C4d evaluation. Recipient HLA antibodies were tested by FlowPRA and Luminex Single Antigen Beads (LSAB). XM were performed by CDC and flow cytometry. Recipient serum was tested for MICA antibodies by LSAB, endothelial cell (EC) antibodies by XM, AT1R antibodies by ELISA, and non-ABO blood group antibodies. Molecular blood typing of the donor DNA was performed. Histopathology identified karyorrhectic nuclear debris in the glomeruli, small fibrin thrombi, and neutrophilic infiltrates, consistent with hyperacute rejection, although IHC failed to show definite C4d deposition. All FlowPRA, XM, LSAB, MICA, and EC XM tests were negative. The AT1R result was 14 U/mL (at risk). Molecular testing confirmed the donor as Group O. Testing ruled out the rare Bombay phenotype, and the recipient was negative for all non-ABO blood group antibodies, except for weak cold agglutinins only seen at 4 °C. The events during the surgery and the pathology findings are consistent with humoral hyperacute rejection. Confoundingly, the recipient has no HLA antibodies and had negative CDC and flow XM with the donor. However, none of the other testing has been able to identify an antibody with a strength that would explain hyperacute rejection. The only identified antibodies thus far are anti-AT1R and cold agglutinins. We are continuing to investigate more non-HLA antibodies that may have a synergistic impact on graft rejection.