Treatment options and strategies for antibody mediated rejection after renal transplantation

Abstract

Antibody mediated rejection is a significant clinical problem encountered in a subset of renal transplant recipients. This type of rejection has a variable pathogenesis from the presence of donor specific antibodies with no overt disease to immediate hyperacute rejection and many variations between. Antibody mediated rejection is more common in human leukocyte antigen sensitized patients. In general, transplant graft survival after antibody mediated rejection is jeopardized, with less than 50% graft survival 5 years after this diagnosis. A variety of agents have been utilized singly and in combinations to treat antibody mediated rejection with differing results and significant research efforts are being placed on developing new targets for intervention. These same agents have been used in desensitization protocols with some success. In this review, we describe the biology of antibody mediated rejection, review the available agents to treat this form of rejection, and highlight areas of ongoing and future research into this difficult clinical problem.

Effect of Pretransplant Rituximab Use on Posttransplant Clinical Outcomes in Patients with High Panel Reactive Antibody Scores

“…Therefore, RTX has a potential role in mediating humoral rejection and improving graft function. In general, transplant graft survival is jeopardized after AMR, with <50% graft survival rate 5 years after this diagnosis [21]. Graft and patients' cumulative survival rates were good in the RTX group.…”

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“…ATG can impact B cells through mechanisms including the resulting decreased interaction between CD4 helper cells and B cells, thus decreasing B cell activation, B cell apoptosis and direct B cell cytoxicity leading to decrease in antibody production [9].…”

“…However, experience with bortezomib is lacking and there is some concern that the onset of its effects might take longer (about 1-to 1.5 months) and therefore its exact place in current algorithms utilized to reduce DSA needs to be determined. At this point it is being used mostly in refractory cases [9].…”

Antibody Mediated Rejection Associated With Complement Factor H–Related Protein 3/1 Deficiency Successfully Treated With Eculizumab

“…Treatment options include elimination of circulating antibody (via plasmapheresis or immunoadsorption), suppression of the T cell response (via antilymphocyte preparations, mycophenolic acid-derived drugs, and/or calcineurin inhibitors), suspected inhibition of residual antibody (via intravenous immunoglobulins [IVIG] or cytomegalovirus hyperimmune globulin [CMV-Ig]), suppression of B cells (via rituximab) and in severe or refractory cases, splenectomy (1,6).…”