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

5As the demand for kidney transplantation is constantly growing methods to expand the donor pool have become increasingly important. AB0-incompatibility has hitherto been regarded as an absolute contraindication to living donor donation. However, as AB0-incompatibility has accounted for the majority of living donor exclusions, efforts have been made to overcome this immunologic barrier. Successful desensitization protocols thus far, have combined plasmapheresis for antibody removal with splenectomy to reduce the antibodyproducing B-cell pool, in addition to quadruple immunosuppression. Although good graft function has been achieved, the high risks involved have been deterrent.

A protocol for AB0-incompatible kidney transplantation based on antigen-specific immunoadsorption and rituximab, in combination with standard maintenance immunosuppression (tacrolimus, mycophenolate mofetil and corticosteroids) was developed. We hypothesized that the anti-A/B antibodies could be effectively eliminated and good graft function achieved, without the complications of coagulopathy and transfusion reactions associated with plasmapheresis. Furthermore, we hypothesized that the substitution of splenectomy 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 2 years. In 38 out of 39 patients the anti-A/B antibodies could be effectively removed and transplantation performed as planned. The antigen-specific immunoadsorption was well tolerated without any serious side effects. Overall patient survival was 97.4% and graft survival 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 transplantation. The incidence of antibody-mediated rejection was 2.6% and there was no significant rebound of anti-A/B antibodies during the study period. However, AB0-incompatible kidney transplantation was associated with an additional cost of approximately 32,000 compared with standard AB0-compatible living donor kidney transplantation.

B-lymphocytes were effectively eliminated long-term in peripheral blood as well as within 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 on antigen-specific immunoadsorption and rituximab, in combination with triple immunosuppressive therapy is safe and effective. AB0-incompatibility following this protocol does not have a negative impact on graft function. AB0-incompatible kidney transplantation using this protocol is equivalent to standard AB0-compatible living donor kidney transplantation.

List of scientific papers

I. Tydén G, Kumlien G, Genberg H, Sandberg J, Lundgren T, Fehrman I (2005). ABO incompatible kidney transplantations without splenectomy, using antigen-specific immunoadsorption and rituximab. Am J Transplant. 5(1): 145-8.
https://doi.org/10.1111/j.1600-6143.2004.00653.x

II. Genberg H, Kumlien G, Wennberg L, Berg U, Tydén G (2008). AB0-incompatible kidney transplantation using antigen-specific immunoadsorption andrituximab: a 3-year follow-up. [Accepted]
https://doi.org/10.1097/TP.0b013e3181726849

III. Genberg H, Kumlien G, Wennberg L, Tydén G (2008). No rebound of A/Bantibodies after AB0-incompatible kidney transplantation using antigen-specific immunoadsorption and rituximab. [Submitted]

IV. Genberg H, Hansson A, Wernerson A, Wennberg L, Tydén G (2006). Pharmacodynamics of rituximab in kidney allotransplantation. Am J Transplant. 6(10): 2418-28.
https://doi.org/10.1111/j.1600-6143.2006.01497.x