@article{3121961,
    title = "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",
    author = "Bellur, S.S. and Roberts, I.S.D. and Troyanov, S. and Royal, V. and Coppo, R. and Cook, H.T. and Cattran, D. and Terroba, Y.A. and Asunis, A.M. and Bajema, I. and Bertoni, E. and Bruijn, J.A. and Cannata-Ortiz, P. and Casartelli, D. and Di Palma, A.M. and Ferrario, F. and Fortunato, M. and Furci, L. and Gakiopoulou, H. and Ljubanovic, D.G. and Giannakakis, K. and Gomá, M. and Gröne, H.-J. and Gutiérrez, E. and Haider, S.A. and Honsova, E. and Ioachim, E. and Karkoszka, H. and Kipgen, D. and Maldyk, J. and Mazzucco, G. and Orhan, D. and Ozluk, Y. and Pantzaki, A. and Perkowska-Ptasinska, A. and Riispere, Z. and Soderberg, M.P. and Steenbergen, E. and Stoppacciaro, A. and Von Feilitzen, B.S. and Tardanico, R. and Tesar, V. and Maixnerova, D. and Lundberg, S. and Gesualdo, L. and Emma, F. and Fuiano, L. and Beltrame, G. and Rollino, C. and Coppo, R. and Amore, A. and Camilla, R. and Peruzzi, L. and Praga, M. and Feriozzi, S. and Polci, R. and Segoloni, G. and Colla, L. and Pani, A. and Angioi, A. and Piras, L. and Feehally, J. and Barratt, J. and Cancarini, G. and Ravera, S. and Durlik, M. and Moggia, E. and Ballarin, J. and Di Giulio, S. and Pugliese, F. and Serriello, I. and Caliskan, Y. and Sever, M. and Locatelli, F. and Del Vecchio, L. and Wetzels, J.F.M. and Peters, H. and Berg, U. and Carvalho, F. and da Costa Ferreira, A.C. and Maggio, M. and Wiecek, A. and Ots-Rosenberg, M. and Magistroni, R. and Topaloglu, R. and Bilginer, Y. and D'Amico, M. and Stangou, M. and Giacchino, F. and Goumenos, D. and Kalliakmani, P. and Gerolymos, M. and Galesic, K. and Geddes, C. and Siamopoulos, K. and Balafa, O. and Galliani, M. and Stratta, P. and Quaglia, M. and Bergia, R. and Cravero, R. and Salvadori, M. and Cirami, L. and Fellstrom, B. and Kloster Smerud, H. and Ferrario, F. and Stellato, T. and Egido, J. and Martin, C. and Floege, J. and Eitner, F. and Lupo, A. and Bernich, P. and Menè, P. and Morosetti, M. and van Kooten, C. and Rabelink, T. and Reinders, M.E.J. and Grinyo, J.M. and Fulladosa, X. and Cusinato, S. and Benozzi, L. and Savoldi, S. and Licata, C. and Mizerska-Wasiak, M. and Roszkowska-Blaim, M. and Martina, G. and Messuerotti, A. and Dal Canton, A. and Esposito, C. and Migotto, C. and Triolo, G. and Mariano, F. and Pozzi, C. and Boero, R. and Kilicaslan, I.",
    journal = "Nephrology Dialysis Transplantation",
    year = "2019",
    volume = "34",
    number = "10",
    pages = "1681-1690",
    publisher = "Oxford University Press",
    issn = "0931-0509, 1460-2385",
    doi = "10.1093/ndt/gfy337",
    keywords = "corticosteroid;  immunosuppressive agent, Article;  clinical feature;  cohort analysis;  controlled study;  disease classification;  disease severity;  focal glomerulosclerosis;  glomerulus filtration rate;  histopathology;  human;  human tissue;  immunoglobulin A nephropathy;  immunosuppressive treatment;  kidney biopsy;  kidney fibrosis;  major clinical study;  medical decision making;  pathologist;  priority journal;  proteinuria;  reproducibility;  retrospective study;  survival;  treatment outcome;  biopsy;  classification;  clinical trial;  immunoglobulin A nephropathy;  multicenter study;  observer variation;  pathology;  patient selection;  prognosis;  statistical model, Biopsy;  Glomerular Filtration Rate;  Glomerulonephritis, IGA;  Humans;  Immunosuppressive Agents;  Models, Statistical;  Observer Variation;  Patient Selection;  Prognosis;  Reproducibility of Results;  Retrospective Studies",
    abstract = "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. © 2018 The Author(s) 2018. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved."
}