Current Perspectives in ABO-Incompatible Kidney Transplant

Abstract

For a long time, ABO incompatible living donor kidney transplantation has been considered contraindicated, due to the presence of isohemagglutinins, natural antibodies reacting with non-self ABO antigens. However, as the demand for kidney transplantation is constantly growing, methods to expand the donor pool have become increasingly important. Thus, in the last decades, specific desensitization strategies for ABOi transplantation have been developed. Nowadays, these regimens consist of transient removal of preformed anti-A or anti-B antibodies by using plasmapheresis or immunoadsorption and B-cell immunity modulation by CD20+ cells depletion with rituximab, in association with maintenance immunosuppression including corticosteroids, tacrolimus and mycophenolate mofetil. The outcome in ABOi kidney transplantation have markedly improved over the years. In fact, although randomized trials are still lacking, recent meta analysis has revealed that there is no difference in terms of graft and patient's survival between ABOi and ABO compatible kidney transplant, even in the long term. However, many concerns still exist, because ABOi kidney transplantation is associated with an increased risk of bleeding and infectious complications, partly related to the effects of extracorporeal treatments and the strong immunosuppression. Thus, a continuous improvement in desensitization strategies, with the aim of minimize the immunosuppressive burden, on the basis of immune pathogenesis, antibodies titers and/or ABO blood group, is warranted. In this review, we discuss the main immune mechanisms involved in ABOi kidney transplantation, the pathogenesis of tolerance and the desensitization regimens, including immunoadsorption and plasmapheresis and the immunosuppressive protocol. Finally, we provide an overview on outcome and future perspectives in ABOi kidney transplant.

Keywords: ABO incompatible kidney transplant; blood group; plasma exchange; rituximab.

Figure 1

The possible pathogenetic mechanism of different B cell response in patients receiving AB0i kidney transplant. Thymus-independent antigens may cause the switch from B1 cells producing low avidity IgM to B2 cells able to produce high levels of complement-fixing IgG1, which can predispose to rejection.

Figure 2

The desensitization strategy performed in ABOi kidney transplant patients. A single infusion of rituximab 375 mg/mq is administrated four weeks before kidney transplant. Two weeks before kidney transplant, patient starts oral immunosuppressive therapy (tacrolimus and mycophenolate mofetil). A variable number of immunoadsorption and/or plasma exchange (PEX) sessions is performed before kidney transplant, until a titer < or = at 1:8 is achieved. The isohemagglutinin titer is measured every day after ABOi kidney transplant and further PEX sessions are performed on demand.