The technique of apheresis has improved and more recently a tailored desensitization proved to be the more efficient strategy avoiding an excess of immunosuppression with the related side effects

The technique of apheresis has improved and more recently a tailored desensitization proved to be the more efficient strategy avoiding an excess of immunosuppression with the related side effects. availability of new drugs. Rituximab has substantially replaced splenectomy. The technique of apheresis has improved and more recently a tailored desensitization proved to be the more efficient strategy avoiding Rabbit Polyclonal to TLE4 an excess of immunosuppression with the related side effects. Recent reports document outcomes for such transplantation similar to the outcomes of standard transplantation. Keywords: ABO-incompatible transplants, Desensitization strategies, Immunological aspects, B cell depletion, Immunomodulation, Apheresis techniques, Kidney paired donation Core tip: Renal transplantation from living donors across different and incompatible ABO-incompatible immunological barriers has become safe and effective in recent years because our improved knowledge of the immune system and the availability of new drugs. Recipient desensitization and kidney paired donation are the two strategies adopted. Among the desensitization tools, a relevant role of rituximab is usually avoiding splenectomy, apheretic L-cysteine techniques eliminate the preformed alloantibodies, and high-dose intravenous immunoglobulins improve the immunomodulation. Several points still remain to be better clarified, but recently the outcomes of these transplants have attained those of standard transplantation. INTRODUCTION Renal transplantation is considered the best therapy for patients affected by end-stage renal disease. To date, the major problems to receiving renal transplantation, in addition to cadaveric renal donor shortage, are that many patients around the wait list have problems because of advanced age, immunological reactivity, or issues related to surgery or cardiovascular disease. For such patients, to avoid a long time on dialysis, transplantation from living donor is the L-cysteine best option. However, approximately 30% of such transplantations are considered incompatible from the immunological point of view either because of the presence in the recipient of antibodies directed against the human leukocyte antigen (HLA) antigens of the donor or because of the incompatibility of the ABO system between the donor and recipient or because of both[1]. There are two principal strategies to overcome these barriers: (1) To desensitize the recipient to remove the antibodies and change the immunological status, allowing the transplant; and (2) To exchange the organs between two or more pairs to exchange the organs between different donors. The aim of this review is usually to give a general overview of ABO incompatibility (ABOi), the techniques used to overcome ABOi, the removal of the immunological barriers, and the outcomes obtained. In the last part of the review, kidney paired donation (KPD) will also be briefly discussed. IMMUNOLOGICAL ASPECTS The antigens of the ABO system are glycoproteins expressed on erythrocyte membranes as well as on epithelial and endothelial cells. At the renal level, these glycoproteins are also expressed around the collecting and distal tubules and on the vascular endothelial cells. The intensity of antigen expression around the tissues is also related to the acute rejection rate in patients with low isoagglutinin levels in the blood[2]. The ABO blood groups consist of four categories (A, B, AB and O). The formation of anti- blood group antibodies occurs against the antigens that are not native to the host. In addition, group O individuals have higher antibody titers to both the A and B antigens. As a consequence, recipients of blood type O have a higher incidence of antibody-mediated rejection (ABMR) after transplantation[3]. In addition to the membrane-linked antigens, circulating epitopes A and B, both soluble and linked to von Willebrand factor exist in some patients. These antigens, when free, are responsible for ABMR[4]. Indeed, better results in transplantation involving ABOi are obtained when transplanting kidneys from A2 donors to O recipients. The A2 subtype does not have circulating antigens linked to von Willebrand factor[5]. The reaction of isoagglutinins with the antigens of the ABO group induces complement activation, as documented by the presence of C4d[6]. In addition to its relation with the development of ABMR, the presence of C4d around the tissues may also be associated with the development of chronic rejection[7,8]. DEVELOPMENT OF THE PRACTICE OF KIDNEY TRANSPLANTATION IN ABO- INCOMPATIBLE PAIRS For a long time, ABOi has been considered an absolute contraindication to kidney transplantation. For the first time, Brynger et al[9] reported the clinical outcomes of 21 renal transplantations from A2 donors to O recipients. Since then, L-cysteine several authors have tried to perform kidney transplantations in pairs with ABOi[10-13]. Principally after 1998, there was a worldwide increase in the rate of.