Antibody‐mediated rejection of renal allograft in combined liver–kidney transplant

Abstract

Liver transplantation is performed based on ABO blood type compatibility without dependence on crossmatch results. Combined liver-kidney transplantation (CLKT) is similarly performed without dependence of crossmatch results as the liver is thought to confer protection to the renal allograft against alloantibody. We report a case of CLKT in a sensitized patient with antibody-mediated rejection (AMR) of the renal allograft. AMR was confirmed with C4d staining and serial monitoring of donor-specific antibody (DSA). Despite intensive therapy directed against AMR and the presence of the liver allograft, the patient demonstrated increasing titers of alloantibody, never demonstrated adequate renal function, and ultimately expired after two months. This result demonstrates the potential for AMR of the renal allograft in sensitized recipients of CLKT.

Preformed and De Novo Donor Specific Antibodies in Visceral Transplantation: Long-Term Outcome With Special Reference to the Liver

“…Another potential mechanism is the simultaneous presence of many donor organs that share the same HLA and potential induction of high dose tolerance. The herein preferential clearance of class‐I DSA has also been reported in a small cohort of combined liver‐kidney recipients consistent with the notion that MHC class‐I are predominantly expressed on hepatocytes (61,62). Failure of the liver to clear some of the preformed DSA could be related to the high antibody titers, high affinity, diminished absorption and/or reduced neutralization.…”

Longterm renal allograft survival after sequential liver‐kidney transplantation from a single living donor

“…Immunoprotection is exerted through the neutralization of cytotoxic T cell activity after the binding of these molecules to the CD8 receptor on T cells . Recently, some studies concerning the implication of donor‐directed antibodies for antibody‐mediated rejection in CLKT have been reported . These results demonstrated that the immunoprotection conferred by the liver graft on the kidney graft was not sufficient, particularly in the presence of class II de novo DSA.…”

Predisposing Factors of Diminished Survival in Simultaneous Liver/Kidney Transplantation

“…Female donor gender also emerged as an individual risk factor for poor patient survival. The pronounced impact of these factors in SLKT highlights the need for judicious patient selection and underscores decisive management of modifiable recipient factors (17,18,30,31). In particular, although no prognostic implications were observed with the use of anti‐IL2R antibodies or lymphocyte depleting agents in SLKT, 8/16 (50%) mortalities within 1 year posttransplant were due to sepsis and refinement of immunosuppressive protocol would be required.…”

“…Although several single center studies of long-term outcomes of SLKT have appeared, they typically included data on a limited number of patients collected over a lengthy period limiting the identification of clear risk factors for impaired patient and graft survival (8)(9)(10)(11)(12). Furthermore, although it has been suggested that simultaneous liver allografting has an immunoprotective effect on the kidney graft, this has not been universally observed (6,9,(11)(12)(13)(14)(15)(16)(17)(18)(19).…”