Antibody mediated rejection (AMR) poses a significant and continued challenge for long term graft survival in kidney transplantation. However, in the recent years, there has emerged an increased understanding of the varied manifestations of the antibody mediated processes in kidney transplantation. In this article, we briefly discuss the various histopathological and clinical manifestations of AMRs, along with describing the techniques and methods which have made it easier to define and diagnose these rejections. We also review the emerging issues of C4d negative AMR, its significance in long term allograft survival and provide a brief summary of the current management strategies for managing AMRs in kidney transplantation. 1. Introduction Antibody-mediated rejection is an important cause of acute and chronic allograft dysfunction and graft loss. Although hyperacute (i.e., preformed antibody-mediated) rejection has been recognized since the 1960s, the role of antibodies in other forms of rejection was not clear until new diagnostic methods became available. Our knowledge about the role of antibodies in allograft rejection, particularly in some forms of chronic allograft rejection, has been evolving rapidly over the last decade. 2. Types of Antibody-Mediated Rejection (AMR) Antibodies directed against donor antigen can cause different types of rejection that can vary in acuity and severity. Hyperacute AMR It occurs due to preformed donor specific antibodies (DSA) present in high titers and presents as graft failure that can occur within minutes (but sometimes may be delayed for a few days) after transplantation [1]. The occurrence of this type of rejection is extremely rare because of the universal adoption of pretransplantation cross-matching. The histopathology is characterized by features of severe endothelial and arterial injury manifested as arteritis (often transmural), interstitial edema, and severe cortical necrosis, with almost all cases requiring allograft nephrectomy. Most of the initial cases were reported in patients with a history of previous transplantation or in multiparous women, suggesting the role of sensitization and preformed antibodies. Strong proof for this was provided by Patel and Terasaki in 1969 when they showed that 24 of the 30 patients with a pretransplant positive crossmatch had immediate graft failure compared with only 8 graft failures in 195 patients without a positive crossmatch [1]. Acute AMR It is characterized by graft dysfunction manifesting over days and is a result of DSAs, that may either be preformed or develop
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