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      Banff survey on antibody‐mediated rejection clinical practices in kidney transplantation: Diagnostic misinterpretation has potential therapeutic implications

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          Abstract

          The aim of this study was to determine how the Banff antibody-mediated rejection (ABMR) classification for kidney transplantation is interpreted in practice and affects therapy. The Banff Antibody-Mediated Injury Workgroup electronically surveyed clinicians and pathologists worldwide regarding diagnosis and treatment for 6 case-based scenarios. The participants' (95 clinicians and 72 renal pathologists) assigned diagnoses were compared to the Banff intended diagnoses (reference standard). The assigned diagnoses and reference standard differed by 26.1% (SD 28.1%) for pathologists and 34.5% (SD 23.3%) for clinicians. The greatest discordance between the reference standard and clinicians' diagnosis was when histologic features of ABMR were present but donor-specific antibody was undetected (49.4% [43/87]). For pathologists, the greatest discordance was in the case of acute/active ABMR C4d staining negative in a positive crossmatch transplant recipient (33.8% [23/68]). Treatment approaches were heterogeneous but linked to the assigned diagnosis. When acute/active ABMR was diagnosed by the clinician, treatment was recommended 95.3% (SD 18.4%) of the time vs only 77.7% (SD 39.2%) of the time when chronic active ABMR was diagnosed (P < .0001). In conclusion, the Banff ABMR classification is vulnerable to misinterpretation, which potentially has patient management implications. Continued efforts are needed to improve the understanding and standardized application of ABMR classification in the transplant community.

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          Most cited references17

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          The Banff 2015 Kidney Meeting Report: Current Challenges in Rejection Classification and Prospects for Adopting Molecular Pathology

          The XIII Banff meeting, held in conjunction the Canadian Society of Transplantation in Vancouver, Canada, reviewed the clinical impact of updates of C4d‐negative antibody‐mediated rejection (ABMR) from the 2013 meeting, reports from active Banff Working Groups, the relationships of donor‐specific antibody tests (anti‐HLA and non‐HLA) with transplant histopathology, and questions of molecular transplant diagnostics. The use of transcriptome gene sets, their resultant diagnostic classifiers, or common key genes to supplement the diagnosis and classification of rejection requires further consensus agreement and validation in biopsies. Newly introduced concepts include the i‐IFTA score, comprising inflammation within areas of fibrosis and atrophy and acceptance of transplant arteriolopathy within the descriptions of chronic active T cell–mediated rejection (TCMR) or chronic ABMR. The pattern of mixed TCMR and ABMR was increasingly recognized. This report also includes improved definitions of TCMR and ABMR in pancreas transplants with specification of vascular lesions and prospects for defining a vascularized composite allograft rejection classification. The goal of the Banff process is ongoing integration of advances in histologic, serologic, and molecular diagnostic techniques to produce a consensus‐based reporting system that offers precise composite scores, accurate routine diagnostics, and applicability to next‐generation clinical trials.
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            International standardization of criteria for the histologic diagnosis of renal allograft rejection: The Banff working classification of kidney transplant pathology

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              A Randomized Trial of Bortezomib in Late Antibody-Mediated Kidney Transplant Rejection

              Late antibody-mediated rejection (ABMR) is a leading cause of kidney allograft failure. Uncontrolled studies have suggested efficacy of the proteasome inhibitor bortezomib, but no systematic trial has been undertaken to support its use in ABMR. In this randomized, placebo-controlled trial (the Bortezomib in Late Antibody-Mediated Kidney Transplant Rejection [BORTEJECT] Trial), we investigated whether two cycles of bortezomib (each cycle: 1.3 mg/m2 intravenously on days 1, 4, 8, and 11) prevent GFR decline by halting the progression of late donor-specific antibody (DSA)-positive ABMR. Forty-four DSA-positive kidney transplant recipients with characteristic ABMR morphology (median time after transplant, 5.0 years; pretransplant DSA documented in 19 recipients), who were identified on cross-sectional screening of 741 patients, were randomly assigned to receive bortezomib (n=21) or placebo (n=23). The 0.5-ml/min per 1.73 m2 per year (95% confidence interval, -4.8 to 5.8) difference detected between bortezomib and placebo in eGFR slope (primary end point) was not significant (P=0.86). We detected no significant differences between bortezomib- and placebo-treated groups in median measured GFR at 24 months (33 versus 42 ml/min per 1.73 m2; P=0.31), 2-year graft survival (81% versus 96%; P=0.12), urinary protein concentration, DSA levels, or morphologic or molecular rejection phenotypes in 24-month follow-up biopsy specimens. Bortezomib, however, associated with gastrointestinal and hematologic toxicity. In conclusion, our trial failed to show that bortezomib prevents GFR loss, improves histologic or molecular disease features, or reduces DSA, despite significant toxicity. Our results reinforce the need for systematic trials to dissect the efficiency and safety of new treatments for late ABMR.
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                Author and article information

                Journal
                American Journal of Transplantation
                Am J Transplant
                Wiley
                1600-6135
                1600-6143
                June 20 2018
                January 2019
                July 19 2018
                January 2019
                : 19
                : 1
                : 123-131
                Affiliations
                [1 ]William J. von Liebig Center for Transplantation and Clinical RegenerationMayo Clinic Rochester MN USA
                [2 ]Centre for Outcomes Research &amp; Evaluation, Research Institute of the McGill University Health Center Montreal QC Canada
                [3 ]Department of Microbiology and Immunology KU Leuven Leuven Belgium
                [4 ]Department of Nephrology University Hospitals Leuven Leuven Belgium
                [5 ]Department of Pathology and Cell BiologyColumbia University Medical Center New York NY USA
                [6 ]Department of PathologyJohns Hopkins University School of Medicine Baltimore MD USA
                [7 ]Department of Transplantation SurgeryYale University School of Medicine New Haven CT USA
                [8 ]Department of Medicine and Clinical Islet Transplant Program University of Alberta Edmonton AB Canada
                [9 ]Department of Pathology Erasmus Medical Center Rotterdam Netherlands
                [10 ]Medstar Georgetown Transplant Institute Washington DC USA
                [11 ]Department of Cardiac Thoracic and Vascular Sciences Transplant Immunology Unit Padua University Hospital Padua Italy
                [12 ]Department of MedicineWeill Cornell Medicine – New York Presbyterian Hospital New York NY USA
                [13 ]Institut d'Incestigacions Biomèdiques August Pi i Sunyer and Kidney Transplant Unit Hospital Clínic Barcelona Spain
                [14 ]Medizinische Klinik mit Schwerpunkt Nephrologie und Internistische Intensivmedizin Charité Universitätsmedizin Berlin Berlin Germany
                [15 ]Department of Pathology and Laboratory MedicineUniversity of Kentucky Lexington KY USA
                [16 ]Department of SurgeryUniversity of CaliforniaSan Francisco School of Medicine San Francisco CA USA
                [17 ]Department of Internal Medicine and Transplantation Erasmus University Medical Center Rotterdam Netherlands
                [18 ]Department of Laboratory Medicine and PathologyMayo Clinic Rochester MN USA
                [19 ]Division of Nephrology/Transplant NephrologyJohns Hopkins University Baltimore MD USA
                Article
                10.1111/ajt.14979
                6309659
                29935060
                9cbbdb1c-1431-4a6a-ab47-36de30d5beee
                © 2019

                http://onlinelibrary.wiley.com/termsAndConditions#vor

                http://doi.wiley.com/10.1002/tdm_license_1.1

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