Reproducibility of the Oxford Classification of IgA nephropathy, impact of biopsy scoring on treatment allocation and clinical relevance of disagreements: evidence from the VALIGA study cohort

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Title: Reproducibility of the Oxford Classification of IgA nephropathy, impact of biopsy scoring on treatment allocation and clinical relevance of disagreements: evidence from the VALIGA study cohort
Authors: Bellur, S
Roberts, ISD
Troyanov, S
Royal, V
Coppo, R
Cook, HT
Cattran, D
Terroba, YA
Asunis, AM
Bajema, I
Bertoni, E
Bruijn, JA
Cannata-Ortiz, P
Casartelli, D
Di Palma, AM
Ferrario, F
Fortunato, M
Furci, L
Gakiopoulou, H
Ljubanovic, DG
Giannakakis, K
Gomà, M
Gröne, H-J
Gutiérrez, E
Haider, SA
Honsova, E
Ioachim, E
Karkoszka, H
Kipgen, D
Maldyk, J
Mazzucco, G
Orhan, D
Ozluk, Y
Pantzaki, A
Perkowska-Ptasinska, A
Riispere, Z
Soderberg, M
Steenbergen, E
Stoppacciaro, A
Sundelin, B
Tardanico, R
Item Type: Journal Article
Abstract: Objective & Methods: The VALIGA study investigated the utility of the Oxford Classification of IgA nephropathy (IgAN) in 1147 patients from 13 European countries. Biopsies were scored by local pathologists followed by central review in Oxford. We had two distinct objectives: to assess how closely pathology findings were associated with the decision to give corticosteroid/immunosuppressive treatments (CS/IS), and to determine the impact of differences in MEST-C scoring between central and local pathologists on the clinical value of the Oxford Classification. We tested for each lesion the associations between the type of agreement (local and central pathologists scoring absent, local present-central absent, local absent-central present, both scoring present) with the initial clinical assessment, as well as long-term outcomes in those patients who did not receive CS/IS. Results: All glomerular lesions (M, E, C and S) assessed by local pathologists were independently associated with the decision to administer CS/IS therapy whilst the severity of tubulointerstitial lesions was not. Reproducibility between local and central pathologists was moderate for S (segmental sclerosis) and T (tubular atrophy/interstitial fibrosis), and poor for M (mesangial hypercellularity), E (endocapillary hypercellularity), and C (crescents). Local pathologists found statistically more of each lesion, except for the S lesion, which was more frequent with central review. Disagreements were more likely to occur when the proportion of glomeruli affected was low. The M lesion, assessed by central pathologists, correlated better with the severity of the disease at presentation and discriminated better with outcomes. By contrast, the E lesion, evaluated by local pathologists, correlated better with the clinical presentation and outcomes compared to central review. Both C and S lesions, when discordant between local and central pathologists, had a clinical phenotype intermediate to double absent lesions (milder disease) and double present (more severe). Conclusion: We conclude that differences in the scoring of MEST-C criteria between local pathologists and central reviewer have a significant impact on the prognostic value of the Oxford Classification. Since the decision to offer immunosuppressive therapy in this cohort was intimately associated with the MEST-C score, this study indicates a need for a more detailed guidance for pathologists in the scoring of IgAN biopsies.
Issue Date: Oct-2019
Date of Acceptance: 18-Sep-2018
ISSN: 0931-0509
Publisher: Oxford University Press (OUP)
Start Page: 1681
End Page: 1690
Journal / Book Title: Nephrology Dialysis Transplantation
Volume: 34
Issue: 10
Copyright Statement: © The Author(s) 2018. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved. This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model ( This is a pre-copy-editing, author-produced version of an article accepted for publication in Nephrology Dialysis Transplantation following peer review. The definitive publisher-authenticated version Shubha S Bellur, Ian S D Roberts, Stéphan Troyanov, Virginie Royal, Rosanna Coppo, H Terence Cook, Daniel Cattran, Yolanda Arce Terroba, Anna Maria Asunis, Ingeborg Bajema, Elisabetta Bertoni, Jan A Bruijn, Pablo Cannata-Ortiz, Donatella Casartelli, Anna Maria Di Palma, Franco Ferrario, Mirella Fortunato, Luciana Furci, Hariklia Gakiopoulou, Danica Galesic Ljubanovic, Konstantinos Giannakakis, Montserrat Gomà, Hermann-Josef Gröne, Eduardo Gutiérrez, S Asma Haider, Eva Honsova, Elli Ioachim, Henryk Karkoszka, David Kipgen, Jagoda Maldyk, Gianna Mazzucco, Diclehan Orhan, Yasemin Ozluk, Afroditi Pantzaki, Agnieszka Perkowska-Ptasinska, Zivili Riispere, Magnus P Soderberg, Eric Steenbergen, Antonella Stoppacciaro, Birgitta Sundelin Von Feilitzen, Regina Tardanico, Reproducibility of the Oxford classification of immunoglobulin A nephropathy, impact of biopsy scoring on treatment allocation and clinical relevance of disagreements: evidence from the VALidation of IGA study cohort, Nephrology Dialysis Transplantation, Volume 34, Issue 10, October 2019, Pages 1681–1690 is available online at:
Keywords: IgA nephropathy
Oxford classification
kidney biopsy
Urology & Nephrology
1103 Clinical Sciences
Publication Status: Published
Online Publication Date: 2018-12-15
Appears in Collections:Department of Immunology and Inflammation

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