Modern approaches to incompatible kidney transplantation.

The presence of human-leukocyte antigen (HLA)-antibodies and blood group incompatibility remain a large barrier to kidney transplantation leading to increased morbidity and mortality on the transplant waiting list. Over the last decade a number of new approaches were developed to overcome these barriers. Intravenous immunoglobulin (IVIG) remains the backbone of HLA desensitization therapy and has been shown in a prospective, randomized, placebo controlled trial to improve transplantation rates. Excellent outcomes with the addition of rituximab (anti-B cell) to IVIG based desensitization have been achieved. There is limited experience with bortezomib (anti-plasma cell) and eculizumab (complement inhibition) for desensitization. However, these agents may be good adjuncts for patients who are broadly sensitized with strong, complement-fixing HLA antibodies. Excellent short and long-term outcomes have been achieved in ABO incompatible transplantation with the combination of antibody removal, B cell depletion, and pre-transplant immunosuppression. Kidney paired donation has emerged as a reasonable alternative for programs who cannot provide desensitization or in conjunction with desensitization. Future therapies directed toward cytokines that alter B cell proliferation are under investigation.