BACKGROUND: The VALidation of IGA (VALIGA) study investigated the utility of the Oxford Classification of immunoglobulin A nephropathy (IgAN) in 1147 patients from 13 European countries. Methods. 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 (CS/IS) treatments, 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 and central absent, local absent and 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, while 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. In contrast, the E lesion, evaluated by local pathologists, correlated better with the clinical presentation and outcomes when compared with 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 a 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.

Alessandro Manzoni Hospital Lecco Italy

Careggi University Hospital Florence Italy

City of the Health and the Science of Turin Health Agency Regina Margherita Children's Hospital Turin Italy

German Cancer Research Center INF 280 Heidelberg Germany

Hacettepe University Institute of Children's Health Ankara Turkey

Hippokration General Hospital Aristotle University of Thessaloniki Thessaloniki Greece

Hôpital du Sacré Coeur de Montréal Montreal Canada

Hôpital Maisonneuve Rosemont Montreal Canada

Hospital Universitari de Bellvitge Barcelona Spain

Imperial College Hammersmith Hospital London UK

ISS Fundación Jiménez Díaz Madrid Spain

Istanbul University Istanbul Turkey

Karolinska Institute Stockholm Sweden

Leiden University Medical Center Leiden The Netherlands

Medical University of Silesia Katowice Poland

Medical University of Warsaw Warsaw Poland

National and Kapodistrian University of Athens Greece Athens Greece

Nephrology Department University Hospital October 12 Madrid Spain

Nephrology Fundacion Puigvert Barcelona Spain

Nephrology Medical School University of Ioannina Ioannina Greece

Nephropathology Radboud University Nijmegen Medical Center Nijmegen The Netherlands

Nephropathology San Gerardo Hospital Monza Italy

Oxford University Hospitals Oxford UK

Pathology Drug Safety and Metabolism IMED Biotech Unit AstraZeneca Gothenburg Sweden

Pathology G Brotzu Hospital Cagliari Italy

Pathology Institute for Clinical and Experimental Medicine Prague Czech Republic

Pathology Leicester General Hospital Leicester UK

Pathology Policlinic of Modena and Reggio Emilia Modena Italy

Pathology S Andrea Hospital Rome Italy

Pathology S Croce Hospital Cuneo Italy

Pathology Tartu University Clinics Tartu Estonia

Pathology University of Turin Italy

Pathology Western Infirmary Glasgow Glasgow UK

Sapienza University of Rome Rome Italy

School of Medicine University Hospital Dubrava University of Zagreb Zagreb Croatia

Spedali Civili di Brescia Brescia Italy

Toronto General Hospital University Health Network Toronto Ontario Canada

Transplantation Medicine and Nephrology Warsaw Medical University Warsaw Poland

University of Bari Bari Italy

Nephrol Dial Transplant. 2019 Oct 1;34(10):1617-1618. doi: 10.1093/ndt/gfz009. PubMed

Nephrol Dial Transplant. 2020 Aug 1;35(8):1453. doi: 10.1093/ndt/gfz001. PubMed

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