Shubha S Bellur1, Ian S D Roberts1, Stéphan Troyanov2, Virginie Royal3, Rosanna Coppo4, H Terence Cook5, Daniel Cattran6, Yolanda Arce Terroba7, Anna Maria Asunis8, Ingeborg Bajema9, Elisabetta Bertoni10, Jan A Bruijn9, Pablo Cannata-Ortiz11, Donatella Casartelli12, Anna Maria Di Palma13, Franco Ferrario14, Mirella Fortunato15, Luciana Furci16, Hariklia Gakiopoulou17, Danica Galesic Ljubanovic18, Konstantinos Giannakakis19, Montserrat Gomà20, Hermann-Josef Gröne21, Eduardo Gutiérrez22, S Asma Haider23, Eva Honsova24, Elli Ioachim25, Henryk Karkoszka26, David Kipgen27, Jagoda Maldyk28, Gianna Mazzucco29, Diclehan Orhan30, Yasemin Ozluk31, Afroditi Pantzaki32, Agnieszka Perkowska-Ptasinska33, Zivili Riispere34, Magnus P Soderberg35, Eric Steenbergen36, Antonella Stoppacciaro37, Birgitta Sundelin Von Feilitzen38, Regina Tardanico39. 1. Oxford University Hospitals, Oxford, UK. 2. Hôpital du Sacré-Coeur de Montréal, Montreal, Canada. 3. Hôpital Maisonneuve-Rosemont, Montreal, Canada. 4. City of the Health and the Science of Turin Health Agency, Regina Margherita Children's Hospital, Turin, Italy. 5. Imperial College, Hammersmith Hospital, London, UK. 6. Toronto General Hospital, University Health Network, Toronto, Ontario, Canada. 7. Nephrology, Fundacion Puigvert, Barcelona, Spain. 8. Pathology, G. Brotzu Hospital, Cagliari, Italy. 9. Leiden University Medical Center, Leiden, The Netherlands. 10. Careggi-University Hospital, Florence, Italy. 11. ISS-Fundación Jiménez Díaz, Madrid, Spain. 12. Alessandro Manzoni Hospital, Lecco, Italy. 13. University of Bari, Bari, Italy. 14. Nephropathology, San Gerardo Hospital, Monza, Italy. 15. Pathology, S. Croce Hospital, Cuneo, Italy. 16. Pathology, Policlinic of Modena and Reggio Emilia, Modena, Italy. 17. National and Kapodistrian University of Athens, Greece, Athens, Greece. 18. School of Medicine, University Hospital Dubrava, University of Zagreb, Zagreb, Croatia. 19. Sapienza University of Rome, Rome, Italy. 20. Hospital Universitari de Bellvitge, Barcelona, Spain. 21. German Cancer Research Center, INF 280, Heidelberg, Germany. 22. Nephrology Department, University Hospital October 12, Madrid, Spain. 23. Pathology, Leicester General Hospital, Leicester, UK. 24. Pathology, Institute for Clinical and Experimental Medicine, Prague, Czech Republic. 25. Nephrology, Medical School University of Ioannina, Ioannina, Greece. 26. Medical University of Silesia, Katowice, Poland. 27. Pathology, Western Infirmary Glasgow, Glasgow, UK. 28. Medical University of Warsaw, Warsaw, Poland. 29. Pathology, University of Turin, Italy. 30. Hacettepe University Institute of Children's Health, Ankara, Turkey. 31. Istanbul University, Istanbul, Turkey. 32. Hippokration General Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece. 33. Transplantation Medicine and Nephrology, Warsaw Medical University, Warsaw, Poland. 34. Pathology, Tartu University Clinics, Tartu, Estonia. 35. Pathology, Drug Safety and Metabolism, IMED Biotech Unit, AstraZeneca, Gothenburg, Sweden. 36. Nephropathology, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands. 37. Pathology S. Andrea Hospital, Rome, Italy. 38. Karolinska Institute, Stockholm, Sweden. 39. Spedali Civili di Brescia, Brescia, Italy.
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.
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.
Authors: Virginie Royal; Jarcy Zee; Qian Liu; Carmen Avila-Casado; Abigail R Smith; Gang Liu; Laura H Mariani; Stephen Hewitt; Lawrence B Holzman; Brenda W Gillespie; Jeffrey B Hodgin; Laura Barisoni Journal: J Am Soc Nephrol Date: 2020-02-21 Impact factor: 10.121
Authors: Jan U Becker; David Mayerich; Meghana Padmanabhan; Jonathan Barratt; Angela Ernst; Peter Boor; Pietro A Cicalese; Chandra Mohan; Hien V Nguyen; Badrinath Roysam Journal: Kidney Int Date: 2020-04-01 Impact factor: 10.612
Authors: Jhonny L Moreno; Lida M Rodas; Juliana Draibe; Xavier Fulladosa; Montserrat Gomá; Adriana Garcia-Herrera; Josep M Cruzado; Joan Torras; Luis F Quintana Journal: Clin Kidney J Date: 2019-11-09
Authors: Mark Haas; James Mirocha; Kerstin Amann; Ingeborg M Bajema; Laura Barisoni; Jan Ulrich Becker; J Charles Jennette; Kenuske Joh; Danica Galesic Ljubanovic; Ian S D Roberts; Joris J Roelofs; Sanjeev Sethi; Raul Suarez; Caihong Zeng; Surya V Seshan Journal: Kidney Int Rep Date: 2021-10-29