AB0-incompatible kidney transplantation using antigen-specific immunoadsorption and rituximab

5As the demand for kidney transplantation is constantly growing methods to expand thedonor pool have become increasingly important. AB0-incompatibility has hitherto been re-garded as an absolute contraindication to living donor donation. However, as AB0-incom-patibility has accounted for the majority of living donor exclusions, efforts have been madeto overcome this immunologic barrier. Successful desensitization protocols thus far, havecombined plasmapheresis for antibody removal with splenectomy to reduce the antibodyproducing B-cell pool, in addition to quadruple immunosuppression. Although good graftfunction has been achieved, the high risks involved have been deterrent. A protocol for AB0-incompatible kidney transplantation based on antigen-specific im-munoadsorption and rituximab, in combination with standard maintenance immunosup-pression (tacrolimus, mycophenolate mofetil and corticosteroids) was developed. We hypo-thesized that the anti-A/B antibodies could be effectively eliminated and good graft func-tion achieved, without the complications of coagulopathy and transfusion reactions associ-ated with plasmapheresis. Furthermore, we hypothesized that the substitution of splenecto-my with a single dose of the B-lymphocyte depleting antibody, rituximab, would abolish thesurgical risk and reduce the risk of infectious complications related to splenectomy. From Sept 2001 to Oct 2007 a total of 39 patients underwent conditioning for AB0-incompatible kidney transplantation according to the protocol. Median follow-up was 2years. In 38 out of 39 patients the anti-A/B antibodies could be effectively removed andtransplantation performed as planned. The antigen-specific immunoadsorption was welltolerated without any serious side effects. Overall patient survival was 97.4% and graftsurvival was 86.8%. Kidney function was evaluated in a short and long term perspective,the results being equivalent to those of AB0-compatible living donor kidney transplanta-tion. The incidence of antibody-mediated rejection was 2.6% and there was no significantrebound of anti-A/B antibodies during the study period. However, AB0-incompatible kid-ney transplantation was associated with an additional cost of approximately 32,000 com-pared with standard AB0-compatible living donor kidney transplantation. B-lymphocytes were effectively eliminated long-term in peripheral blood as well as wit-hin the kidney transplant. In the lymphoid compartment, the B-lymphocytes were reduced.Despite B-lymphocyte depletion, there was no increased risk of infection following AB0-incompatible kidney transplantation compared with AB0-compatible transplantation. We conclude that AB0-incompatible kidney transplantation using a protocol based onantigen-specific immunoadsorption and rituximab, in combination with triple immuno-suppressive therapy is safe and effective. AB0-incompatibility following this protocol doesnot have a negative impact on graft function. AB0-incompatible kidney transplantation usingthis protocol is equivalent to standard AB0-compatible living donor kidney transplantation