ABO-Incompatible Kidney Transplantation: Overview and New Strategies

The increasing shortage of human organs for transplantation has regained interest in blood group ABO-incompatible kidney transplantation, especially living donor kidney transplantation. After being performed at a few centers during the 1980s, ABO-incompatible renal transplantation has continued to expand over the years. More than 1000 ABO-incompatible living donor transplantations have been performed during the last decade in Europe, Japan, and the USA. Today, most centers use anti-ABO antibody removal combined with slightly different immunosuppressive drug protocols based on anti-CD20 (rituximab), tacrolimus, mycophenolate mofetil, and steroids. Splenectomy, once considered a prerequisite for ABO-incompatible transplantation, is now being replaced by anti-CD20 monoclonal antibody and this has, together with carbohydrate antigen-based immunoadsorption of anti-A/B antibodies, contributed to the expanded ABO-incompatible living donor programs. The short-term results of these new protocols are, so far, excellent with very few graft losses. In the years to come, the expanding clinical experience will tell which pretransplant regime will be optimal and the long-term graft survival outcome. Controlled trials are so far lacking and will, most likely, not be performed. Despite being successful in the short term, there are still a number of clinical as well as scientific issues to be addressed. The pretransplant anti-ABO antibody titer target level to allow a safe transplantation is still not determined and more efficient immunoadsorbent material to remove anti-A/B antibodies are expected to be developed. Our knowledge of the molecular mechanisms behind the accommodation phenomenon where anti-ABO antibodies return without graft damage is not known. Knowledge gained within ABO incompatibility has been applied to allow transplantation of HLA-sensitized patients and may be of value in the development of xenotransplantation. Paired kidney donation is another way of overcoming recipient/donor blood group ABO incompatibility and will probably expand. However, this concept has mainly ethical and logistic aspects, since the individual recipient immune system is not challenged with incompatible blood groups antigens. (Trends in Transplant 2007;1:61-8) Corresponding author: Gunnela Nordén, [email protected]