*Purpose: In simultaneous liver-kidney transplantation (SLKT) in highly-sensitized patients, donor specific anti-HLA antibodies (DSA) can be present prior to transplant leading to positive crossmatch, yet these recipients have minimal antibody mediated rejection. The mechanisms and timing underlying these immunologic changes remain unknown. We aimed to delineate the intra-operative kinetics of anti-HLA antibodies in highly sensitized SLKT recipients. We hypothesized that antibody levels would decrease after reperfusion of the liver allograft.

*Methods: Sensitized SLKT candidates with documented DSA were identified (n=4). Anti-HLA antibody profiles were created and flow-cytometric and complement-dependent cytotoxic (CDC) crossmatches were performed. Liver and kidney transplantation was performed sequentially as a single operation. Samples were collected at five time points: prior to induction, during the anhepatic phase, after completion of the bile duct, after reperfusion of the kidney, and the first postoperative day (POD1).

*Results: There was a significant reduction (mean decrease 85%, p<0.05) in class I DSA to near undetectable levels during the anhepatic phase that persisted through POD1. This effect was most pronounced in patients with positive pre-operative CDC crossmatches. Intra-operative changes in class II DSA and non-DSA anti-HLA antibodies were not significant.

*Conclusions: Contrary to our hypothesis, significant reductions in DSA were seen in the anhepatic phase of SLKT, prior to reperfusion of the liver allograft. This effect was specific to class I DSA; class II DSA and non-DSA anti-HLA antibodies remained relatively unchanged throughout the peri-operative period. The underlying mechanism of this phenomenon remains to be elucidated, but may be related to changes in circulating complement.

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