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      The Banff 2017 Kidney Meeting Report: Revised diagnostic criteria for chronic active T cell–mediated rejection, antibody‐mediated rejection, and prospects for integrative endpoints for next‐generation clinical trials

      meeting-report
      1 , , 2 , , 3 , 4 , 3 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 2 , 12 , 13 , 14 , 2 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 19 , 22 , 23 , 11 , 24 , 24
      American Journal of Transplantation
      John Wiley and Sons Inc.
      classification systems: Banff classification, kidney transplantation/nephrology, molecular biology, pathology/histopathology, rejection, translational research/science

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          Abstract

          The kidney sessions of the 2017 Banff Conference focused on 2 areas: clinical implications of inflammation in areas of interstitial fibrosis and tubular atrophy (i‐ IFTA) and its relationship to T cell–mediated rejection ( TCMR), and the continued evolution of molecular diagnostics, particularly in the diagnosis of antibody‐mediated rejection ( ABMR). In confirmation of previous studies, it was independently demonstrated by 2 groups that i‐ IFTA is associated with reduced graft survival. Furthermore, these groups presented that i‐ IFTA, particularly when involving >25% of sclerotic cortex in association with tubulitis, is often a sequela of acute TCMR in association with underimmunosuppression. The classification was thus revised to include moderate i‐ IFTA plus moderate or severe tubulitis as diagnostic of chronic active TCMR. Other studies demonstrated that certain molecular classifiers improve diagnosis of ABMR beyond what is possible with histology, C4d, and detection of donor‐specific antibodies ( DSAs) and that both C4d and validated molecular assays can serve as potential alternatives and/or complements to DSAs in the diagnosis of ABMR. The Banff ABMR criteria are thus updated to include these alternatives. Finally, the present report paves the way for the Banff scheme to be part of an integrative approach for defining surrogate endpoints in next‐generation clinical trials.

          Abstract

          The Banff consortium presents revisions to the diagnostic criteria for T cell– and antibody‐mediated kidney transplant rejection, including specific criteria for chronic active T cell–mediated rejection, plus prospects for integrative endpoints in clinical trials. See related articles on pages 321, 364, and 377.

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          Most cited references32

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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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            Belatacept and Long-Term Outcomes in Kidney Transplantation

            In previous analyses of BENEFIT, a phase 3 study, belatacept-based immunosuppression, as compared with cyclosporine-based immunosuppression, was associated with similar patient and graft survival and significantly improved renal function in kidney-transplant recipients. Here we present the final results from this study.
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              A phase III study of belatacept-based immunosuppression regimens versus cyclosporine in renal transplant recipients (BENEFIT study).

              Belatacept, a costimulation blocker, may preserve renal function and improve long-term outcomes versus calcineurin inhibitors in kidney transplantation. This Phase III study (Belatacept Evaluation of Nephroprotection and Efficacy as First-line Immunosuppression Trial) assessed a more intensive (MI) or less intensive (LI) regimen of belatacept versus cyclosporine in adults receiving a kidney transplant from living or standard criteria deceased donors. The co-primary endpoints at 12 months were patient/graft survival, a composite renal impairment endpoint (percent with a measured glomerular filtration rate (mGFR) or =10 mL/min/1.73 m(2) Month 3-Month 12) and the incidence of acute rejection. At Month 12, both belatacept regimens had similar patient/graft survival versus cyclosporine (MI: 95%, LI: 97% and cyclosporine: 93%), and were associated with superior renal function as measured by the composite renal impairment endpoint (MI: 55%; LI: 54% and cyclosporine: 78%; p < or = 0.001 MI or LI versus cyclosporine) and by the mGFR (65, 63 and 50 mL/min for MI, LI and cyclosporine; p < or = 0.001 MI or LI versus cyclosporine). Belatacept patients experienced a higher incidence (MI: 22%, LI: 17% and cyclosporine: 7%) and grade of acute rejection episodes. Safety was generally similar between groups, but posttransplant lymphoproliferative disorder was more common in the belatacept groups. Belatacept was associated with superior renal function and similar patient/graft survival versus cyclosporine at 1 year posttransplant, despite a higher rate of early acute rejection.
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                Author and article information

                Contributors
                mark.haas@cshs.org
                alexandreloupy@gmail.com
                Journal
                Am J Transplant
                Am. J. Transplant
                10.1111/(ISSN)1600-6143
                AJT
                American Journal of Transplantation
                John Wiley and Sons Inc. (Hoboken )
                1600-6135
                1600-6143
                21 January 2018
                February 2018
                : 18
                : 2 ( doiID: 10.1111/ajt.2018.18.issue-2 )
                : 293-307
                Affiliations
                [ 1 ] Department of Pathology and Laboratory Medicine Cedars‐Sinai Medical Center Los Angeles CA USA
                [ 2 ] Paris Translational Research Center for Organ Transplantation INSERM U970 and Necker Hospital University Paris Descartes Paris France
                [ 3 ] Paris Translational Research Center for Organ Transplantation and Department of Nephrology and Transplantation Hopital Saint Louis Université Paris VII and INSERM U 1160 Paris France
                [ 4 ] Department of Medicine Imperial College London and North West London Pathology London UK
                [ 5 ] Nephrology Department Hospital Vall d'Hebron Autonomous University of Barcelona Barcelona Spain
                [ 6 ] Department of Renal Medicine Westmead Hospital Sydney Australia
                [ 7 ] Alberta Transplant Applied Genomics Centre University of Alberta Edmonton Alberta Canada
                [ 8 ] Department of Pathology Massachusetts General Hospital Harvard Medical School Boston MA USA
                [ 9 ] Montefiore‐Einstein Center for Transplantation Montefiore Medical Center Bronx NY USA
                [ 10 ] Department of Medicine Section of Nephrology Johns Hopkins University School of Medicine Baltimore MD USA
                [ 11 ] Department of Pathology Johns Hopkins University School of Medicine Baltimore MD USA
                [ 12 ] Division of Nephrology Department of Medical Specialities Geneva University Hospitals Geneva Switzerland
                [ 13 ] Institute of Pathology University Hospital of Cologne Cologne Germany
                [ 14 ] Department of Laboratory Medicine and Pathology Mayo Clinic Rochester MN USA
                [ 15 ] Department of Pathology University of Manitoba Winnipeg Canada
                [ 16 ] Division of Nephrology Department of Medicine Johns Hopkins University Baltimore MD USA
                [ 17 ] Division of Nephrology Department of Medicine University of Alabama School of Medicine Birmingham AL USA
                [ 18 ] Department of Microbiology and Immunology University of Leuven & Department of Nephrology University Hospitals Leuven Leuven Belgium
                [ 19 ] Division of Nephropathology Department of Pathology and Laboratory Medicine The University of North Carolina School of Medicine Chapel Hill NC USA
                [ 20 ] Department of Internal Medicine and Immunology University of Manitoba Winnipeg Canada
                [ 21 ] Department of Surgery Johns Hopkins Medical Institutions Baltimore MD USA
                [ 22 ] Departments of Surgery and Immunology Mayo Clinic Rochester MN USA
                [ 23 ] Division of Transplantation Pathology Thomas E. Starzl Transplantation Institute University of Pittsburgh Pittsburgh PA USA
                [ 24 ] Department of Laboratory Medicine and Pathology University of Alberta Edmonton Canada
                Author notes
                [*] [* ] Correspondence

                Mark Haas and Alexandre Loupy

                Email: mark.haas@ 123456cshs.org ; alexandreloupy@ 123456gmail.com

                Author information
                http://orcid.org/0000-0003-1371-1947
                http://orcid.org/0000-0003-3697-3886
                Article
                AJT14625
                10.1111/ajt.14625
                5817248
                29243394
                f8f8e07e-155d-45d1-9451-875bfda675d5
                © 2017 The Authors. American Journal of Transplantation published by Wiley Periodicals, Inc. on behalf of The American Society of Transplantation and the American Society of Transplant Surgeons

                This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

                History
                : 05 November 2017
                : 06 December 2017
                : 07 December 2017
                Page count
                Figures: 2, Tables: 6, Pages: 15, Words: 11007
                Categories
                Meeting Report
                Meeting Reports
                Custom metadata
                2.0
                ajt14625
                February 2018
                Converter:WILEY_ML3GV2_TO_NLMPMC version:version=5.3.2.2 mode:remove_FC converted:19.02.2018

                Transplantation
                classification systems: banff classification,kidney transplantation/nephrology,molecular biology,pathology/histopathology,rejection,translational research/science

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