Proposed combined assay reached 89 % sensitivity and 76 % specificity for rejection. Conclusion ABMR is recognized as a major obstacle to improvement of long-term kidney allograft survival. marker for diagnosis of graft rejection, and LTBP1 thus might serve as a liquid biopsy in the near future. Despite all achievements, diagnosing ABMR in kidney allografts remains to be a challenge in a significant number of cases. Keywords: Kidney transplantation, Antibody-mediated rejection, Donor-specific antibodies, Banff classification, Rejection diagnostics Introduction Kidney transplantation represents a treatment of choice for end-stage renal disease (ESRD) with a significantly higher graft survival rate and lower treatment costs compared to hemodialysis (Kramer et al. 2020). Over the past two decades, short-term graft survival has significantly improved due to advances in immunosuppressive regimens, but long-term kidney graft survival has remained largely unchanged. Apart from recurrence of the original disease Calcium D-Panthotenate in the graft, a Calcium D-Panthotenate major cause of kidney transplant failure is usually chronic antibody-mediated rejection (ABMR) (Parajuli et al. 2019). In this review, we aim to summarize some of the recent findings in the field of ABMR pathology and diagnostics. Pathogenesis of antibody-mediated rejection Recently, it has been reported that a number of kidney transplant waitlist patients show detectable levels of anti-HLA antibodies due to previous pregnancy, blood transfusion, prior transplantation or as a result of heterologous immunity (Mumford et al. 2021). Antibody-mediated rejection is the consequence of an conversation between the recipients antibodies and antigens localized on donor endothelium. These antibodies are either donor-specific anti-HLA antibodies, or non-HLA anti-endothelial cell antibodies (Fichtner et al. 2021). Phenotypes of ABMR have been conventionally defined as hyperacute, acute and chronic. Donor-specific antibodies may be preformed or develop de-novo after transplantation. ABMR may be caused by donor-specific antibodies direct cytotoxic effect, complement activation or complement impartial recruitment of leukocytes (Garg et al. 2017). Hyperacute rejection occurs within hours after reperfusion because of the presence of high levels of preformed complement fixing antibodies. This worst case scenario was frequently observed at pioneer occasions and at present it represents a rare event resulting from a false-negative result of complement-dependent cytotoxicity crossmatch (CDC) test performed just before surgery. Aside from such a rare complication, many transplantations are performed despite a minor HLA barrier when DSA levels are too low to cause positivity of CDC or flow cytometric crossmatch assessments (Amrouche et al. 2017). Moreover, memory B-cells may play Calcium D-Panthotenate a role in antibody development shortly after transplantation as well (Luque et al. 2019). DSA may also occur de novo later after transplantation, mostly as a result of inadequate immunosuppression (Mohammed et al. 2021). Both the preformed and the de novo DSA are associated with the development of chronic active antibody-mediated rejection. This obtaining is characterized by basal membrane multilayering, progressive scarring and fibrosis, leading to glomerular loss, proteinuria and graft dysfunction (Zhang et al. 2018). Over the past 5 years, another mechanism of IgG impartial inflammatory cell recruitment and complement Calcium D-Panthotenate independent endothelial damage has been described and will be discussed later (Charreau et al. 2021). Classification of kidney allograft rejection The most commonly used rejection classification is usually that according to the Banff Working Group (Schinstock et al. 2021). The group started getting together with in 1991 in Banff, Canada, and originally consisted of pathologists, nephrologists and surgeons with expertise in the field of organ transplantation, and their goal was to define the clinical and histological criteria of kidney transplant rejection (Solez et al. 1993). The internationally recognized diagnostic standard used at present, the Banff classification, is based on the discussions that were led at the biennial meetings (Table 1). The Banff classification is used not only in the field of kidney transplantation, but in the field of other solid organ transplantation as well, and the expert panel has also adopted immunologic, genetic and transcriptomic data (Loupy et al. 2020). Table 1 Evolution of ABMR diagnostic criteria during Banff meetings where significant changes were involved 1991 Hyperacute rejection C rejection presumed to be due to preformed antibody 1997 Antibody-mediated rejection C rejection demonstrated to be due, at least in part, to anti-donor antibody?A. Immediate (hyperacute)?B. Delayed (accelerated acute) 2001 Defined 3 grades of ABMR?I. ATN-like (minimal inflammation), C4d+?II. Capillary-margination and/or thromboses, C4d+?III. Arterial C v3, C4d+Documented DSASuspicious for ABMR when DSA not detected 2013 Acute/active ABMR, all three features must be present for diagnosis?I. Histologic evidence of acute tissue injury C microvascular inflammation, intimal arteritis, thrombotic microangiopathy, acute tubular injury?II. Evidence of recent antibody interaction with endothelium??a. C4d staining in peritubular capillaries??b. At least moderate microvascular inflammation??c. Increased expression of transcripts indicative of endothelial injury?III. Serologic evidence of DSAs 2015.