There is a need for improvement of the detection and treatment of the antibody-mediated graft rejection for ABO-incompatible kidney transplant recipients. With the development of novel pre-conditioning protocols, which employ anti-CD20 antibody, therapeutic plasma exchange plus extracorporeal immunoadsorption and standard immunosuppression application, together with the use of more sensitive and objective assays for immunological monitoring, patients that were not candidates for kidney transplant in the past, are now being transplanted. We have designed a pre-conditioning protocol for ABO-incompatible kidney transplants based on TPE plus our own simple "closed-circuit" immunoadsorption technique - combined by anti-CD20, standard immunosuppressive treatment, and without splenectomy. The results obtained in this study strongly support our hypothesis leading to the conclusion that this protocol can be used successfully, with high-quality ABO antibody depletion (p<0.001) and beneficial clinical findings. The application of this protocol is safe, and not associated with alteration in normal plasma constituent levels or with occurrence of any side effects of apheresis or clinical consequences. Finally, this pre-conditioning protocol radically reduces the treatment-cost. Definitive conclusions can only be drawn from larger, randomized, controlled clinical trials.