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

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 Mark Haas Alexandre Loupy Carmen Lefaucheur Candice Roufosse Denis Glotz Daniel Serón Brian J. Nankivell Philip F. Halloran Robert B. Colvin Enver Akalin Nada Alachkar Serena M. Bagnasco Yassine Bouatou Jan U. Becker Lynn D. Cornell J.P. Duong Van Huyen Ian W. Gibson Edward S. Kraus Roslyn B. Mannon Maarten Naesens Volker Nickeleit Peter Nickerson Dorry L. Segev Harsharan K. Singh Mark D. Stegall Parmjeet Randhawa Lorraine C. Racusen Kim Solez Michael Mengel

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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 2018 American Journal of Transplantation 10.1111/ajt.14625 haas2018-the-banff-2017-kidney-meeting-repo haas2018-the-banff-2017-kidney-meeting-repo.txt, the project's staged copy 74ac52e49beee6b2d232b26437b6f9bdfb9bb6a4 cc-by-nc medicine

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0 spans located by searching the stored text for the quote's exact words, allowing any whitespace between them A DIAGNOSTIC CLASSIFICATION REVISING ITSELF IN PUBLIC - the fourteenth biennial Banff conference, which changed the criteria for two categories of kidney transplant rejection, named each revision by its meeting year, and published a survey of how its own users apply the previous version Quotation withheld because this record is not cleared for redistribution. whether inflammation in areas of fibrosis and atrophy (i-IFTA) should be admitted to the classification as diagnostic of chronic active TCMR, and at what thresholds Quotation withheld because this record is not cleared for redistribution. the 2017 revisions: tubulointerstitial criteria for chronic active TCMR added at i-IFTA 2-3 with tubulitis t2-3, ABMR criteria widened to admit C4d and validated molecular assays as alternatives to donor-specific antibodies, and the word 'acute' deleted from the ABMR category names Quotation withheld because this record is not cleared for redistribution. method Quotation withheld because this record is not cleared for redistribution. a controlled vocabulary whose own authors apply it non-uniformly, revised by consensus every two years against evidence that arrives between meetings Quotation withheld because this record is not cleared for redistribution. expert-consensus expert-consensus Quotation withheld because this record is not cleared for redistribution. THE VOCABULARY'S OWN AUTHORS DO NOT APPLY IT UNIFORMLY, AND THE PAPER SAYS SO IN ITS OWN WORKING-GROUP REPORT: `Survey among renal pathologists (including very experienced) revealed nonuniform application of current Banff TCMR cutoffs, consideration of non-Banff lesions in TCMR diagnosis, grading or nongrading of i-IFTA.` This corpus has records of vocabularies that failed on measurement (laubach2018) and of definitions that disagreed across papers; this is a body measuring the DISPERSION OF ITS OWN USERS and printing the result Quotation withheld because this record is not cleared for redistribution. AND A WORD WAS REMOVED FROM THE CLASSIFICATION FOR A COMMUNICATIVE REASON, NOT A SCIENTIFIC ONE: `The term `ACUTE` (in acute/active ABMR) is confusing to clinicians, and consequently it has been removed from the Banff classification`. Nothing about the disease changed. The term was deleted because readers misread it - the same shape as macdonald2015 (WHO SAGE taking the narrower name for the broader concept for institutional reasons) and the ICTV's published change types, and the plainest case in the corpus of a definition edited for its AUDIENCE Quotation withheld because this record is not cleared for redistribution. AND THE SURVEY SAYS HOW THE VOCABULARY IS MISREAD, NOT ONLY THAT IT IS: `Clinicians often fail to recognize chronic elements of ABMR (eg, cg >0)` and are `more likely to consider a diagnosis of chronic, active ABMR if C4d is negative, even if there is no TG, PTCBML, or IFTA`. A named direction of error against a named criterion Quotation withheld because this record is not cleared for redistribution. AND A FEATURE EXCLUDED IN 1991 WAS ADMITTED IN 2017 BECAUSE THE POPULATION CHANGED, NOT THE FEATURE: `The nonspecificity of i-IFTA for rejection, proved by the fact that it occurs in native kidneys, was the main reason why i-IFTA and tubulitis in atrophic tubules was specifically excluded from the classification at the first Banff meeting. However, since 1991, immunosuppression has changed and graft survival improved with more patients presenting late posttransplantation with i-IFTA.` The lesion is exactly as nonspecific as it was; what moved is who gets biopsied Quotation withheld because this record is not cleared for redistribution. AND A CATEGORY WAS DELIBERATELY NOT CREATED, BECAUSE ITS ANALOGUE PROVED UNDEFINABLE: `there is no borderline or suspicious category for chronic active TCMR, particularly as this category within acute TCMR has proved to be troublesome for treating clinicians and even for pathologists to define`. An absence with a stated reason - a committee declining to mint a term because the existing one of that shape does not work Quotation withheld because this record is not cleared for redistribution. AND A LABELLING RULE EXISTS TO STOP THE SAME BIOPSY BEING COUNTED TWICE: `a biopsy fulfilling the diagnostic criteria for chronic active TCMR should not be given A SECOND DIAGNOSIS of Borderline or acute TCMR, because the latter already addresses the acute/ACTIVE COMPONENT` - while `biopsies with chronic active TCMR can have an additional diagnosis of ABMR`. Which co-diagnoses are permitted is part of the definition, and it is stated separately from the criteria Quotation withheld because this record is not cleared for redistribution. AND THE MARKER PROPOSED AS A TRIAL ENDPOINT HAS THE SAME PROBLEM ONE LAYER DOWN: `current shortcomings of DSA testing (variability in test methods, diagnostic threshold definitions, clinical significance standards) are known to limit its utility as a sole endpoint`, with `Quotation withheld`. The definitional instability the meeting exists to fix in histology is present, unfixed, in the biomarker offered to replace it Quotation withheld because this record is not cleared for redistribution. THE LESION ADMITTED TO THE CLASSIFICATION IS NOT SPECIFIC AND THE PAPER SAYS SO BEFORE ADMITTING IT: `Clearly, i-IFTA is not a specific lesion, and adding i-IFTA by itself, even if moderate to severe, to the classification as diagnostic of chronic active TCMR does not appear warranted based on present data. It is well known that many other disease processes, including BK virus infection, pyelonephritis, ABMR, recurrent glomerulonephritis, and obstruction, may at some point present with i-IFTA.` The criterion is therefore a CONJUNCTION with tubulitis plus an exclusion list, not the lesion alone Quotation withheld because this record is not cleared for redistribution. AND THE THRESHOLDS ARE SET WHERE THE OUTCOME ASSOCIATION STARTS, IN ONE COHORT: `i-IFTA scores of 2 and 3, but not 1, as well as t2 and t3 tubulitis (but not t1) within areas of IFTA, excluding severely atrophic tubules, were associated with an increased rate of graft loss.` The class boundary is drawn at the point where a prognostic signal appears - the same move as the ARF/AKI classifications in this corpus, and it inherits that cohort's population Quotation withheld because this record is not cleared for redistribution. and the committee names its own strategy rather than presenting the choice as forced: `This conservative approach has served the Banff group well in the past, with the introduction of C4d-negative ABMR. As with the latter, future modifications will be considered as new data emerge`. The classification is explicitly provisional, with the revision mechanism part of the publication Quotation withheld because this record is not cleared for redistribution. and the agreement figure behind the new criterion is three pathologists in one centre: `the Paris group reported GOOD AGREEMENT AMONG 3 PATHOLOGISTS in grading i-IFTA according to the Banff 2015 criteria, with complete agreement between all 3 PATHOLOGISTS IN 101 (67%) OF 150 CASES, and a KAPPA VALUE OF .62` - which is reported as good, and sits below this project's own controlled-vocabulary kappa of 0.702 Quotation withheld because this record is not cleared for redistribution. the occurrence of i-IFTA in NATIVE (non-transplanted) kidneys - a population in which rejection is impossible eliminates: the reading of i-IFTA as a rejection-specific lesion; it is the negative control that kept the lesion out of the classification for 26 years · outcome: held Quotation withheld because this record is not cleared for redistribution. requiring tubulitis (t2-3) ALONGSIDE i-IFTA (2-3), inflammation in >25% of total cortex, and explicit exclusion of chronic pyelonephritis and BK nephropathy eliminates: overdiagnosis of chronic active TCMR from a lesion the paper calls nonspecific in the same section · outcome: held Quotation withheld because this record is not cleared for redistribution. grading of i-IFTA by 3 pathologists against the Banff 2015 criteria eliminates: the objection that i-IFTA cannot be scored reproducibly, 'as scattered inflammatory cells are often seen in what might be considered by many pathologists to be bland fibrosis' · outcome: partial Quotation withheld because this record is not cleared for redistribution. chronic active TCMR chronic active TCMR Quotation withheld because this record is not cleared for redistribution. acute TCMR acute TCMR Quotation withheld because this record is not cleared for redistribution. borderline borderline Quotation withheld because this record is not cleared for redistribution. i‐IFTA i‐IFTA Quotation withheld because this record is not cleared for redistribution. tubulitis tubulitis Quotation withheld because this record is not cleared for redistribution. titration titration Quotation withheld because this record is not cleared for redistribution. mean fluorescence intensity mean fluorescence intensity Quotation withheld because this record is not cleared for redistribution. `chronic active TCMR` (Banff 2017) - EXTENDED to the tubulointerstitial compartment: i-IFTA score 2-3 WITH tubulitis t2-3 in all but severely atrophic tubules, inflammation in >25% of total cortex, and other causes of i-IFTA ruled out. Banff 2015 named the entity in the vascular compartment only Quotation withheld because this record is not cleared for redistribution. `acute/active ABMR` (before 2017) vs `active ABMR` (2017 on) - THE SAME CATEGORY WITH A WORD DELETED, `because the term `acute` ... is confusing to clinicians` Quotation withheld because this record is not cleared for redistribution. `i-IFTA` - `inflammation in areas of interstitial fibrosis and tubular atrophy`: `EXCLUDED from the classification` in 1991 for nonspecificity, admitted in 2017 in conjunction with tubulitis Quotation withheld because this record is not cleared for redistribution. `borderline` - a category that exists WITHIN acute TCMR and was deliberately NOT created for chronic active TCMR, because the existing one `has proved to be troublesome for treating clinicians and even for pathologists to define` Quotation withheld because this record is not cleared for redistribution. extends → the Banff 2015 meeting report, which named chronic active TCMR in the vascular compartment but gave no criteria for the tubulointerstitial one Quotation withheld because this record is not cleared for redistribution. extends → the first Banff meeting of 1991, which specifically EXCLUDED i-IFTA and tubulitis in atrophic tubules from the classification - this report reverses that exclusion and gives the reason Quotation withheld because this record is not cleared for redistribution. chronic active TCMR —distinct-from→ acute TCMR chronic active TCMR acute TCMR the relation itself is separately evidenced · strength of the relation: 0.95 · note: 'a biopsy fulfilling…' - the two categories are kept apart by a rule about co-diagnosis, not by a difference in lesion · the relation stated: the two categories are kept apart by a rule about CO-DIAGNOSIS: a biopsy meeting the chronic active criteria may NOT also be called Borderline or acute TCMR Quotation withheld because this record is not cleared for redistribution. titration —contrasted-with→ mean fluorescence intensity titration mean fluorescence intensity the relation itself is separately evidenced · strength of the relation: 0.95 · note: 'TITRATION RATHER…' - two readouts of the same antibody, one preferred because the other has a ceiling. The instrument's dynamic range decides which number the endpoint is made of · the relation stated: two readouts of the same antibody, one preferred RATHER THAN the other because the other saturates Quotation withheld because this record is not cleared for redistribution. borderline —part-of→ acute TCMR borderline acute TCMR the relation itself is separately evidenced · strength of the relation: 0.85 · note: 'there is NO BORDERLINE…' - the borderline category belongs to acute TCMR and was deliberately withheld from the new one. Weight 0.85: the clause asserts the containment in a subordinate aside, in the course of denying its twin · the relation stated: the borderline category exists WITHIN acute TCMR - asserted in the aside that denies the same category to chronic active TCMR Audit 2026-09-28: DOUBTFUL - read against its span and kept, but the borderline category exists within acute TCMR; part-of is loose. Quotation withheld because this record is not cleared for redistribution. THE VOCABULARY'S OWN AUTHORS APPLY IT NON-UNIFORMLY, MEASURED AND PRINTED: `Survey among renal pathologists (including very experienced) revealed nonuniform application of current Banff TCMR cutoffs, consideration of non-Banff lesions in TCMR diagnosis, grading or nongrading of i-IFTA` THE VOCABULARY'S OWN AUTHORS APPLY IT NON-UNIFORMLY, MEASURED AND PRINTED: `Survey among renal pathologists (including very experienced) revealed nonuniform application of current Banff TCMR cutoffs, consideration of non-Banff lesions in TCMR diagnosis, grading or nongrading of i-IFTA` Quotation withheld because this record is not cleared for redistribution. A WORD DELETED FROM A DIAGNOSTIC CLASSIFICATION FOR A COMMUNICATIVE REASON: `The term `ACUTE` (in acute/active ABMR) is confusing to clinicians, and consequently it has been removed from the Banff classification` A WORD DELETED FROM A DIAGNOSTIC CLASSIFICATION FOR A COMMUNICATIVE REASON: `The term `ACUTE` (in acute/active ABMR) is confusing to clinicians, and consequently it has been removed from the Banff classification` Quotation withheld because this record is not cleared for redistribution. AND THE DIRECTION OF THE MISREADING IS NAMED: `Clinicians often fail to recognize chronic elements of ABMR` and are `more likely to consider a diagnosis of chronic, active ABMR if C4d is negative, even if there is no TG, PTCBML, or IFTA` AND THE DIRECTION OF THE MISREADING IS NAMED: `Clinicians often fail to recognize chronic elements of ABMR` and are `more likely to consider a diagnosis of chronic, active ABMR if C4d is negative, even if there is no TG, PTCBML, or IFTA` Quotation withheld because this record is not cleared for redistribution. A FEATURE EXCLUDED IN 1991 AND ADMITTED IN 2017 BECAUSE THE POPULATION CHANGED: `The NONSPECIFICITY of i-IFTA for rejection, proved by the fact that it occurs in native kidneys, was the MAIN REASON WHY [it] WAS SPECIFICALLY EXCLUDED ... at the first Banff meeting. However, since 1991, immunosuppression has changed` A FEATURE EXCLUDED IN 1991 AND ADMITTED IN 2017 BECAUSE THE POPULATION CHANGED: `The NONSPECIFICITY of i-IFTA for rejection, proved by the fact that it occurs in native kidneys, was the MAIN REASON WHY [it] WAS SPECIFICALLY EXCLUDED ... at the first Banff meeting. However, since 1991, immunosuppression has changed` Quotation withheld because this record is not cleared for redistribution. A CATEGORY DELIBERATELY NOT CREATED, WITH THE REASON GIVEN: `there is no borderline or suspicious category for chronic active TCMR, particularly as this category within acute TCMR has proved to be troublesome for treating clinicians and even for pathologists to define` A CATEGORY DELIBERATELY NOT CREATED, WITH THE REASON GIVEN: `there is no borderline or suspicious category for chronic active TCMR, particularly as this category within acute TCMR has proved to be troublesome for treating clinicians and even for pathologists to define` Quotation withheld because this record is not cleared for redistribution. AND THE BIOMARKER OFFERED AS A TRIAL ENDPOINT CARRIES THE SAME DEFECT: `current shortcomings of DSA testing (variability in test methods, diagnostic threshold definitions, clinical significance standards) are known to limit its utility as a sole endpoint` AND THE BIOMARKER OFFERED AS A TRIAL ENDPOINT CARRIES THE SAME DEFECT: `current shortcomings of DSA testing (variability in test methods, diagnostic threshold definitions, clinical significance standards) are known to limit its utility as a sole endpoint` Quotation withheld because this record is not cleared for redistribution. `a combination of i-IFTA and tubulitis involving all but severely atrophic tubules, with moderately high thresholds for both (i-IFTA2-3; t2-3), a requirement for inflammation involving >25% of the total cortex present, and other differential diagnoses known to be associated with i-IFTA (eg, chronic pyelonephritis, BK nephropathy) being ruled out` chronic active TCMR Quotation withheld because this record is not cleared for redistribution. the exclusion inside the criterion: tubulitis counts in all but severely atrophic tubules, so the lesion is defined partly by which tubules do not count severely atrophic tubules Quotation withheld because this record is not cleared for redistribution. `complete agreement between all 3 PATHOLOGISTS IN 101 (67%) OF 150 CASES, and a KAPPA VALUE OF .62` - reported as `good agreement`, and the basis for admitting the lesion to the classification inter-rater agreement on i-IFTA grading Quotation withheld because this record is not cleared for redistribution. the extent requirement that sits alongside the two score thresholds cortical inflammation required for chronic active TCMR Quotation withheld because this record is not cleared for redistribution. `i-IFTA scores of 2 and 3, but not 1, as well as t2 and t3 tubulitis (but not t1) ... were associated with an increased rate of graft loss` - the class boundary drawn where the prognostic signal begins i-IFTA and tubulitis thresholds Quotation withheld because this record is not cleared for redistribution. the agreement statistic the new criterion rests on, at .62 across 3 pathologists and 150 cases kappa Quotation withheld because this record is not cleared for redistribution. the semiquantitative score whose threshold (2-3 rather than 1) decides whether a biopsy is chronic active TCMR i-IFTA score Quotation withheld because this record is not cleared for redistribution.

The full text of this article is not redistributable, so it is not included here. The evidence sentences are withheld with it; the tag layer and its grounding status remain. The article itself is at https://doi.org/10.1111/ajt.14625.