4^th World Kidney Congress

Kidney transplantation (KTx) is the treatment of choice for well-selected patients with end-stage renal disease (ESRD) as it improves both quality of life and life expectancy (1,2). However, although it is well documented that KTx and particularly pre-emptive KTx, should be considered as optimal regarding patient’s survival, the steadily growing shortage of kidney transplants makes that approach unrealistic. In order to overpass that problem, several strategies have evolved: (i) KTx with “borderline” donors, (ii) KTx with non-heart beating donors, (iii) ABO-incompatible (ABOi) KTx, (iv) KTx across a positive cross-match, (v) kidney paired donation, and (vi)

altruistic donation. The first series of 26 successful ABOi KTx was reported by Alexandre et al in 1987 (3). Recipient’s desensitization included splenectomy, immunosuppression with steroids,

cyclosporine, azathioprine, and anti-thymocyte globulin, as well as donor-derived platelets transfusion. Since 1989, ABOi KTx has been extensively implemented in Japan because of a religious-driven limited deceased organ donation. From there comes the largest published study including 1878 ABOi KTxs performed from 1989 to

2010 (4). Recipient’s desensitization included plasmapheresis (PP) or other apheresis technique, immunosuppression with steroids, calcineurin inhibitors, antimetabolites, antilymphocyte globulin, cyclophosphamide or deoxyspergualin in various combinations, and anticoagulation. Splenectomy had been performed in 98% of the

cases during the earlier era (1989-2000), in the recent era (2001-2010) it has been subsequently substituted by rituximab. Graft survival rates for the first year improved from 82% in the earlier era to 96% in the recent era. Given the promising results been published by the Japanese, similar protocols have been gradually implemented in the USA and Europe since the mid-1990s. The mainstay of all

preconditioning regimens is the removal of preformed isohaemagglutinin antibodies (by PP, double-filtration plasmapheresis, specific and non-specific immunoadsorption) and the prevention of formation of new ones (earlier by splenectomy, later by rituximab, intravenous immunoglobulins).

Graft survival time seems to be equivalent between ABOi and ABO-compatible (ABOc) transplant recipients in various studies (5, 6). In a recent meta-analysis (7) of divergent studies, it was concluded that “ABOi KTx has very good outcomes, albeit inferior to ABOc KTx”, but still better than remaining on dialysis or receiving a deceased donor kidney transplant. Major complications include infections which is the leading cause of death, antibody-mediated rejection and bleeding. The optimal pretransplantation isohaemagglutinin titre is still debatable. It is of note, that blood group A2 is less antigenemic and that minor incompatibility constellations

against A2 antigen have been safely transplanted without desensitization. Nevertheless, a safe pretransplantation isohaemagglutinin titre has been reported as ≤1/8 albeit with deviation depending on the centre, the measurement method used and the acceptable cut-off values. Flow cytometry has been proved to be the most reliable and reproducible technique for measurement of isohaemagglutinin titre (8). The reason why isohaemagglutinins against recipient’s blood type antigens are detected in the peripheral blood soon after KTx but no antibody-antigen reaction is recorded has been attributed to a phenomenon called “accommodation”. So far, the mechanism behind that phenomenon has been remaining elusive and speculative. Today, ABO-i KTx accounts for approximately 30% of all living donor kidney transplantations performed in Japan. Despite the wide implementation as well as the good results, there are still questions to be answered, such as (i) What is the best method to measure the isohaemagglutinin titre? What are the acceptable titres before as well as after desensitization? (ii) What is the most efficacious and safest

procedure for the removal of preformed antibodies? (iii) Is the administration of rituximab mandatory in all cases? (iv) What is the role of intravenous immunoglobulins? Is there a connection to the increased bleeding complications after transplantation? (v) What are the mechanisms of the phenomenon called “accommodation”? (vi) What is the role of newer molecules (eculizumab, abase,F7508) in the prevention of acute humoral rejection?