The Banff 2019 Kidney Meeting Report (I): Updates on and clarification of criteria for T cell- and antibody-mediated rejection

doi:10.1111/ajt.15898

. 2020 Sep;20(9):2318-2331.

doi: 10.1111/ajt.15898. Epub 2020 May 28.

The Banff 2019 Kidney Meeting Report (I): Updates on and clarification of criteria for T cell- and antibody-mediated rejection

Alexandre Loupy¹, Mark Haas², Candice Roufosse³, Maarten Naesens^{4

5}, Benjamin Adam⁶, Marjan Afrouzian⁷, Enver Akalin⁸, Nada Alachkar⁹, Serena Bagnasco¹⁰, Jan U Becker¹¹, Lynn D Cornell¹², Marian C Clahsen-van Groningen¹³, Anthony J Demetris¹⁴, Duska Dragun¹⁵, Jean-Paul Duong van Huyen¹, Alton B Farris¹⁶, Agnes B Fogo¹⁷, Ian W Gibson¹⁸, Denis Glotz¹⁹, Juliette Gueguen¹, Zeljko Kikic²⁰, Nicolas Kozakowski²⁰, Edward Kraus⁹, Carmen Lefaucheur¹⁹, Helen Liapis²¹, Roslyn B Mannon²², Robert A Montgomery²³, Brian J Nankivell²⁴, Volker Nickeleit²⁵, Peter Nickerson²⁶, Marion Rabant¹, Lorraine Racusen¹⁰, Parmjeet Randhawa¹⁴, Blaise Robin¹, Ivy A Rosales²⁷, Ruth Sapir-Pichhadze²⁸, Carrie A Schinstock²⁹, Daniel Seron³⁰, Harsharan K Singh²⁵, Rex N Smith²⁷, Mark D Stegall³¹, Adriana Zeevi¹⁴, Kim Solez⁶, Robert B Colvin²⁷, Michael Mengel⁶

Affiliations

¹ Université de Paris, INSERM U970, University of Paris, Paris Translational Research Centre for Organ Transplantation, Paris and Necker Hospital, Assistance Publique - Hopitaux de Paris, Paris, France.
² Department of Pathology and Laboratory Medicine, Cedars-Sinai Medical Center, Los Angeles, California, USA.
³ Department of Immunology and Inflammation, Imperial College London and North West London Pathology, London, UK.
⁴ Department of Microbiology and Immunology, University of Leuven, Leuven, Belgium.
⁵ Department of Nephrology, University Hospitals Leuven, Leuven, Belgium.
⁶ Department of Laboratory Medicine and Pathology, University of Alberta, Edmonton, Canada.
⁷ Department of Pathology, University of Texas Medical Branch, Galveston, Texas, USA.
⁸ Montefiore-Einstein Center for Transplantation, Montefiore Medical Center, Bronx, New York, USA.
⁹ Department of Medicine, Division of Nephrology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
¹⁰ Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
¹¹ Institute of Pathology, University Hospital of Cologne, Cologne, Germany.
¹² Division of Anatomic Pathology, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, USA.
¹³ Department of Pathology, Erasmus MC, Rotterdam, the Netherlands.
¹⁴ Department of Pathology, The Thomas E Starzl Transplantation Institute, University of Pittsburgh, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
¹⁵ Department of Nephrology and Critical Care Medicine, Berlin Institute of Health, Charite Universitätsmedizin, Berlin, Germany.
¹⁶ Emory University, Atlanta, Georgia, USA.
¹⁷ Departments of Pathology, Microbiology, and Immunology; Medicine and Pediatrics, Vanderbilt University, Nashville, Tennessee, USA.
¹⁸ Department of Pathology, University of Manitoba, Winnipeg, Canada.
¹⁹ Paris Translational Research Center for Organ Transplantation, Department of Nephrology and Transplantation, Hopital Saint Louis, Université Paris VII, INSERM U 1160, Paris, France.
²⁰ Departments of Medicine and Pathology, Medical University of Vienna, Vienna, Austria.
²¹ Department of Pathology & Immunology & Internal Medicine (Renal) Retired, Washington University School of Medicine, Saint Louis, Missouri, USA.
²² Division of Nephrology, Department of Medicine, University of Alabama School of Medicine, Birmingham, Alabama, USA.
²³ New York University Langone Medical Center, NYU Langone Transplant Institute, New York, New York, USA.
²⁴ Department of Renal Medicine, Westmead Hospital, Sydney, Australia.
²⁵ Division of Nephropathology, Department of Pathology and Laboratory Medicine, The University of North Carolina, Chapel Hill, North Carolina, USA.
²⁶ Department of Internal Medicine and Immunology, University of Manitoba, Winnipeg, Canada.
²⁷ Department of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.
²⁸ Division of Experimental Medicine, Department of Medicine, McGill University, Montreal, Canada.
²⁹ William J. von Liebig Center for Transplantation and Clinical Regeneration, Mayo Clinic, Rochester, Minnesota, USA.
³⁰ Nephrology Department, Hospital Vall d'Hebron, Autonomous University of Barcelona, Barcelona, Spain.
³¹ Departments of Surgery and Immunology, Mayo Clinic, Rochester, Minnesota, USA.

PMID: 32463180
PMCID: PMC7496245
DOI: 10.1111/ajt.15898

The Banff 2019 Kidney Meeting Report (I): Updates on and clarification of criteria for T cell- and antibody-mediated rejection

Alexandre Loupy et al. Am J Transplant. 2020 Sep.

. 2020 Sep;20(9):2318-2331.

doi: 10.1111/ajt.15898. Epub 2020 May 28.

Authors

Affiliations

¹ Université de Paris, INSERM U970, University of Paris, Paris Translational Research Centre for Organ Transplantation, Paris and Necker Hospital, Assistance Publique - Hopitaux de Paris, Paris, France.
² Department of Pathology and Laboratory Medicine, Cedars-Sinai Medical Center, Los Angeles, California, USA.
³ Department of Immunology and Inflammation, Imperial College London and North West London Pathology, London, UK.
⁴ Department of Microbiology and Immunology, University of Leuven, Leuven, Belgium.
⁵ Department of Nephrology, University Hospitals Leuven, Leuven, Belgium.
⁶ Department of Laboratory Medicine and Pathology, University of Alberta, Edmonton, Canada.
⁷ Department of Pathology, University of Texas Medical Branch, Galveston, Texas, USA.
⁸ Montefiore-Einstein Center for Transplantation, Montefiore Medical Center, Bronx, New York, USA.
⁹ Department of Medicine, Division of Nephrology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
¹⁰ Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
¹¹ Institute of Pathology, University Hospital of Cologne, Cologne, Germany.
¹² Division of Anatomic Pathology, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, USA.
¹³ Department of Pathology, Erasmus MC, Rotterdam, the Netherlands.
¹⁴ Department of Pathology, The Thomas E Starzl Transplantation Institute, University of Pittsburgh, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
¹⁵ Department of Nephrology and Critical Care Medicine, Berlin Institute of Health, Charite Universitätsmedizin, Berlin, Germany.
¹⁶ Emory University, Atlanta, Georgia, USA.
¹⁷ Departments of Pathology, Microbiology, and Immunology; Medicine and Pediatrics, Vanderbilt University, Nashville, Tennessee, USA.
¹⁸ Department of Pathology, University of Manitoba, Winnipeg, Canada.
¹⁹ Paris Translational Research Center for Organ Transplantation, Department of Nephrology and Transplantation, Hopital Saint Louis, Université Paris VII, INSERM U 1160, Paris, France.
²⁰ Departments of Medicine and Pathology, Medical University of Vienna, Vienna, Austria.
²¹ Department of Pathology & Immunology & Internal Medicine (Renal) Retired, Washington University School of Medicine, Saint Louis, Missouri, USA.
²² Division of Nephrology, Department of Medicine, University of Alabama School of Medicine, Birmingham, Alabama, USA.
²³ New York University Langone Medical Center, NYU Langone Transplant Institute, New York, New York, USA.
²⁴ Department of Renal Medicine, Westmead Hospital, Sydney, Australia.
²⁵ Division of Nephropathology, Department of Pathology and Laboratory Medicine, The University of North Carolina, Chapel Hill, North Carolina, USA.
²⁶ Department of Internal Medicine and Immunology, University of Manitoba, Winnipeg, Canada.
²⁷ Department of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.
²⁸ Division of Experimental Medicine, Department of Medicine, McGill University, Montreal, Canada.
²⁹ William J. von Liebig Center for Transplantation and Clinical Regeneration, Mayo Clinic, Rochester, Minnesota, USA.
³⁰ Nephrology Department, Hospital Vall d'Hebron, Autonomous University of Barcelona, Barcelona, Spain.
³¹ Departments of Surgery and Immunology, Mayo Clinic, Rochester, Minnesota, USA.

PMID: 32463180
PMCID: PMC7496245
DOI: 10.1111/ajt.15898

Abstract

The XV. Banff conference for allograft pathology was held in conjunction with the annual meeting of the American Society for Histocompatibility and Immunogenetics in Pittsburgh, PA (USA) and focused on refining recent updates to the classification, advances from the Banff working groups, and standardization of molecular diagnostics. This report on kidney transplant pathology details clarifications and refinements to the criteria for chronic active (CA) T cell-mediated rejection (TCMR), borderline, and antibody-mediated rejection (ABMR). The main focus of kidney sessions was on how to address biopsies meeting criteria for CA TCMR plus borderline or acute TCMR. Recent studies on the clinical impact of borderline infiltrates were also presented to clarify whether the threshold for interstitial inflammation in diagnosis of borderline should be i0 or i1. Sessions on ABMR focused on biopsies showing microvascular inflammation in the absence of C4d staining or detectable donor-specific antibodies; the potential value of molecular diagnostics in such cases and recommendations for use of the latter in the setting of solid organ transplantation are presented in the accompanying meeting report. Finally, several speakers discussed the capabilities of artificial intelligence and the potential for use of machine learning algorithms in diagnosis and personalized therapeutics in solid organ transplantation.

Keywords: classification systems: Banff classification; clinical decision-making; clinical research/practice; kidney (allograft) function/dysfunction; kidney transplantation/nephrology; molecular biology: mRNA/mRNA expression; pathology/histopathology; rejection; translational research/science.

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Conflict of interest statement

The authors of this manuscript have conflicts of interest to disclose as described by the American Journal of Transplantation. Michael Mengel received honoraria from Novartis, CSL Behring, and Vitaeris. Mark Haas received consulting fees from Shire ViroPharma, AstraZeneca, Novartis, and CareDx, and honoraria from CareDx. Denis Glotz received honoraria from Sanofi and CSL Behring and consulting fees from BMS and Atara. Roslyn Mannon has received grant funding from CSL Behring, CareDX, Vitaeris, Astellas, and Transplant Genomics, and honoraria from Hansa, Novartis, CSL Behring, and Vitaeris. Robert Colvin is a consultant for Shire ViroPharma, CSL Behring, Alexion, and eGenesis. AJ Demetris is consultant for Novartis and TransMedics, Robert Montgomery received honoraria, consulting fees, or travel expenses from Alexion, Hansa Medical, CSL Behring, Sanofi, Novartis, Viela Bio, Vitaeris Bio, Terasaki Foundation, and Shire/Takeda.

Figures

**Figure 1**
Responses to TTS survey regarding the management of chronic active (CA) TCMR: of the 128 respondents to this survey, 47 (37%) were from Europe, 26 (20%) from Asia, 23 (18%) from the United States and Canada, 18 (14%) from Latin America, 9 (7%) from the Middle East and Africa, and 5 (4%) from Australia and New Zealand. Sixty‐five percent of centers performed <100 renal transplantations annually; 12% performed >200. At all but 12% of centers, biopsies were read by a renal or transplant pathologist

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References

1. Loupy A, Haas M, Solez K, et al. The Banff 2015 Kidney Meeting Report: current challenges in rejection classification and prospects for adopting molecular pathology. Am J Transplant. 2017;17(1):28‐41. - PMC - PubMed
1. Loupy A, Aubert O, Orandi BJ, et al. Prediction system for risk of allograft loss in patients receiving kidney transplants: international derivation and validation study. BMJ. 2019;366:l4923. - PMC - PubMed
1. Kozakowski N, Herkner H, Böhmig GA, et al. The diffuse extent of peritubular capillaritis in renal allograft rejection is an independent risk factor for graft loss. Kidney Int. 2015;88:332‐340. - PubMed
1. Kozakowski N, Herkner H, Eskandary F, et al. An integrative approach for the assessment of peritubular capillaritis extent and score in low‐grade microvascular inflammation – associations with transplant glomerulopathy and graft loss. Nephrol Dial Transplant. 2019;34:166‐217. - PubMed
1. Haas M, Loupy A, Lefaucheur C, et al. 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. Am J Transplant. 2018;18(2):293‐307. - PMC - PubMed

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[1] Loupy A, Haas M, Solez K, et al. The Banff 2015 Kidney Meeting Report: current challenges in rejection classification and prospects for adopting molecular pathology. Am J Transplant. 2017;17(1):28‐41. - PMC - PubMed

[2] Loupy A, Haas M, Solez K, et al. The Banff 2015 Kidney Meeting Report: current challenges in rejection classification and prospects for adopting molecular pathology. Am J Transplant. 2017;17(1):28‐41. - PMC - PubMed

[3] Loupy A, Aubert O, Orandi BJ, et al. Prediction system for risk of allograft loss in patients receiving kidney transplants: international derivation and validation study. BMJ. 2019;366:l4923. - PMC - PubMed

[4] Loupy A, Aubert O, Orandi BJ, et al. Prediction system for risk of allograft loss in patients receiving kidney transplants: international derivation and validation study. BMJ. 2019;366:l4923. - PMC - PubMed

[5] Kozakowski N, Herkner H, Böhmig GA, et al. The diffuse extent of peritubular capillaritis in renal allograft rejection is an independent risk factor for graft loss. Kidney Int. 2015;88:332‐340. - PubMed

[6] Kozakowski N, Herkner H, Böhmig GA, et al. The diffuse extent of peritubular capillaritis in renal allograft rejection is an independent risk factor for graft loss. Kidney Int. 2015;88:332‐340. - PubMed

[7] Kozakowski N, Herkner H, Eskandary F, et al. An integrative approach for the assessment of peritubular capillaritis extent and score in low‐grade microvascular inflammation – associations with transplant glomerulopathy and graft loss. Nephrol Dial Transplant. 2019;34:166‐217. - PubMed

[8] Kozakowski N, Herkner H, Eskandary F, et al. An integrative approach for the assessment of peritubular capillaritis extent and score in low‐grade microvascular inflammation – associations with transplant glomerulopathy and graft loss. Nephrol Dial Transplant. 2019;34:166‐217. - PubMed

[9] Haas M, Loupy A, Lefaucheur C, et al. 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. Am J Transplant. 2018;18(2):293‐307. - PMC - PubMed

[10] Haas M, Loupy A, Lefaucheur C, et al. 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. Am J Transplant. 2018;18(2):293‐307. - PMC - PubMed

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The Banff 2019 Kidney Meeting Report (I): Updates on and clarification of criteria for T cell- and antibody-mediated rejection

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The Banff 2019 Kidney Meeting Report (I): Updates on and clarification of criteria for T cell- and antibody-mediated rejection

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