Does the Liver Truly Protect? Antibody-Mediated Rejection in Simultaneous Liver-Kidney Transplantation

Introduction: Due to the risk of rejection, a positive B & T cell crossmatch is often an absolute contraindication to kidney transplantation. However, a simultaneous liver-kidney transplantation (SLKT) is often performed despite the presence of donor-specific HLA antibodies (DSA) and even positive crossmatch results. Although the exact mechanisms have not been fully elucidated, it has been hypothesized that the liver provides protection to the kidney allograft through immunoabsorption of circulating antibodies by either cell-bound or soluble HLA antigen present in the liver, or through the phagocytic activity of Kuffer cells. We illustrate a patient who developed acute antibody mediated rejection (AMR) of the renal allograft despite undergoing a relatively low immunological risk procedure with SLKT. Case Description: A 56 y/o F with ESKD on HD due to ADPKD and partial hepatectomy due to liver cysts presented for a SLKT. Her intraoperative course was complicated by shock, requiring multiple blood products and a duodenal injury from significant adhesion of polycystic liver to the duodenum. Her CPRA was 100% with a positive B & T cell crossmatch. She received methylprednisolone for induction and was started on Tacrolimus and Mycophenolate mofetil for immunosuppression. She developed delayed graft function (DGF) and underwent a renal biopsy on POD 21. This was consistent with active antibody mediated rejection (vascular rejection with no interstitial inflammation). The MMDx (gene expression profiling) also supported this diagnosis. She received pulse dose steroids, six sessions of plasmapheresis and IVIG with resolution of DGF. Discussion: Previous studies demonstrated a protective effect of the liver allograft against pre-formed antibodies in SLKT. Class I DSA are preferentially cleared compared to class II DSA. Class II DSA are associated with higher risks of rejection, especially with high Median Florescence Intensity (>10,000). Our case highlights these unique factors and the importance of having an individualized approach to highly sensitized, crossmatch positive SLK patients. Early AMR must be taken into consideration in high-risk patients. We had clinical improvement without the use of adjunctive therapies (thymoglobulin, rituximab, splenectomy). However, more studies are needed to determine the optimal treatment and monitoring for AMR in SLKT.