Is there long-term value of pathology scoring in immunoglobulin A nephropathy? A validation study of the Oxford Classification for IgA Nephropathy (VALIGA) update
Rosanna Coppo(Fondazione Ricerca Molinette), Graziella D’Arrigo(Istituto di Fisiologia Clinica), Giovanni Tripepi(Istituto di Fisiologia Clinica), María Luisa Russo(Fondazione Ricerca Molinette), Ian S.D. Roberts(University of Oxford), Shubha S. Bellur(University of Oxford), Daniel C. Cattran(University of Toronto), Terence Cook(Imperial College London), John Feehally(Leicester General Hospital), Vladimı́r Tesař(General University Hospital in Prague), Dita Maixnerová(General University Hospital in Prague), Licia Peruzzi(Ospedale Regina Margherita), Alessandro Amore(Ospedale Regina Margherita), Sigrid Lundberg(Karolinska Institutet), Anna Maria Di Palma(University of Bari Aldo Moro), Loreto Gesualdo(University of Bari Aldo Moro), Francesco Emma(Bambino Gesù Children's Hospital), Cristiana Rollino, Manuel Praga, Luigi Biancone, Antonello Pani(University of Cagliari), Sandro Feriozzi(Ospedale di Belcolle), Rosaria Polci(Ospedale di Belcolle), Jonathan Barratt(Leicester General Hospital), Lucia Del Vecchio, Francesco Locatelli, Alessandro Pierucci(Sapienza University of Rome), Yaşar Çalışkan(Istanbul University), Agnieszka Perkowska‐Ptasińska(Medical University of Warsaw), Magdalena Durlik(Medical University of Warsaw), Elisabetta Moggia(Azienda Sanitaria Ospedaliera S.Croce e Carle Cuneo), José Ballarín(Puigvert Foundation), Jack F.M. Wetzels(Radboud University Nijmegen), Dimitris Goumenos(General University Hospital of Patras), Marios Papasotiriou(General University Hospital of Patras), Kres̆imir Gales̃ić(University Hospital Dubrava), Luka Torić(University Hospital Dubrava), Αikaterini Papagianni(Aristotle University of Thessaloniki), Μaria Stangou(Aristotle University of Thessaloniki), Luisa Benozzi, Stefano Cusinato, Ulla Berg(Integrated Cardio Metabolic Centre), Rezan Topaloğlu(Hacettepe University), M. Maggio, Mai Ots-Rosenberg(Tartu University Hospital), Marco DʼAmico(Ospedale Sant'Anna), Colin Geddes(Queen Elizabeth University Hospital), Olga Balafa(University of Ioannina), Marco Quaglia(Università degli Studi del Piemonte Orientale “Amedeo Avogadro”), Raffaella Cravero(Ospedale degli Infermi), Calogero Lino Cirami(Azienda Ospedaliero-Universitaria Careggi), Bengt Fellström(Uppsala University), Jürgen Floege(RWTH Aachen University), Jesús Egido(Centro de Investigación Biomédica en Red Diabetes y Enfermedades Metabólicas Asociadas), Francesca Mallamaci(Istituto di Fisiologia Clinica), Carmine Zoccali(Istituto di Fisiologia Clinica), for the ERA-EDTA Immunonephrology Working Group(General University Hospital in Prague), Vladimı́r Tesař(General University Hospital in Prague), Dita Maixnerová(Karolinska Institutet), Sigrid Lundberg(Karolinska Institutet), Loreto Gesualdo(Bambino Gesù Children's Hospital), Francesco Emma(Istituto di Fisiologia Clinica), Laura Fuiano(Centro de Investigación Biomédica en Red Diabetes y Enfermedades Metabólicas Asociadas), G. Beltrame, Cristiana Rollino(Fondazione Ricerca Molinette), Rosanna Coppo(Fondazione Ricerca Molinette), Alessandro Amore(Istituto di Fisiologia Clinica), Roberta Camilla(Ospedale Regina Margherita), Licia Peruzzi(Ospedale Regina Margherita), Manuel Praga(Ospedale di Belcolle), Sandro Feriozzi(Ospedale di Belcolle), Rosaria Polci(Centro de Investigación Biomédica en Red Diabetes y Enfermedades Metabólicas Asociadas), Giuseppe Segoloni(Istituto di Fisiologia Clinica), Loredana Colla(University of Cagliari), Antonello Pani(University of Cagliari), Andrea Angioi(Istituto di Fisiologia Clinica), Lisa Adele Piras(Leicester General Hospital), John Feehally(Leicester General Hospital), Giovanni Cancarini(Istituto di Fisiologia Clinica), S. Ravera(Medical University of Warsaw), Magdalena Durlik(Medical University of Warsaw), Elisabetta Moggia(Azienda Sanitaria Ospedaliera S.Croce e Carle Cuneo), José Ballarín(Istituto di Fisiologia Clinica), S. Di Giulio(Istituto di Fisiologia Clinica), Francesco Pugliese(Istituto di Fisiologia Clinica), I. Serriello(Istanbul University), Y Caliskan(Istituto di Fisiologia Clinica), Mehmet Şükrü Sever(Istituto di Fisiologia Clinica), İşın Kiliçaslan, Francesco Locatelli, Lucia Del Vecchio(Radboud University Nijmegen), Jack F.M. Wetzels(Radboud University Nijmegen), Harm Peters(Integrated Cardio Metabolic Centre), U. Berg(Integrated Cardio Metabolic Centre), Fernanda Carvalho(Istituto di Fisiologia Clinica), A.C. da Costa Ferreira, M. Maggio, Andrzej Więcek(Tartu University Hospital), Mai Ots-Rosenberg(Tartu University Hospital), Riccardo Magistroni(Hacettepe University), Rezan Topaloğlu(Hacettepe University), Yelda Bilginer(Ospedale Sant'Anna), Maurizio D’Amico(Aristotle University of Thessaloniki), Μaria Stangou(Aristotle University of Thessaloniki), F Giacchino(General University Hospital of Patras), Dimitrios Goumenos(General University Hospital of Patras), M Papastirou(University Hospital Dubrava), Kres̆imir Gales̃ić(University Hospital Dubrava), Luka Torić(University Hospital Dubrava), Colin Geddes(Aristotle University of Thessaloniki), Konstantinos Siamopoulos(University of Ioannina), Olga Balafa(University of Ioannina), Marco Galliani(Hacettepe University), Piero Stratta(Università degli Studi del Piemonte Orientale “Amedeo Avogadro”), Marco Quaglia(Università degli Studi del Piemonte Orientale “Amedeo Avogadro”), R Bergia(Ospedale degli Infermi), Raffaella Cravero(Istituto di Fisiologia Clinica), Maurizio Salvadori(Azienda Ospedaliero-Universitaria Careggi), Lino Cirami(Uppsala University), Bengt Fellström(Uppsala University), Hilde Kloster Smerud(Istituto di Fisiologia Clinica), Franco Ferrario(Uppsala University), T. Stellato(Centro de Investigación Biomédica en Red Diabetes y Enfermedades Metabólicas Asociadas), Jesús Egido(Centro de Investigación Biomédica en Red Diabetes y Enfermedades Metabólicas Asociadas), Christopher Martin(RWTH Aachen University), J. Floege(Istituto di Fisiologia Clinica), Frank Eitner(Uppsala University), Thomas Rauen, Antonio Lupo(Hacettepe University), Patrizia Bernich(Hacettepe University), Paolo Mené(Istituto di Fisiologia Clinica), Massimo Morosetti(Istituto di Fisiologia Clinica), Cees van Kooten(Uppsala University), Ton J. Rabelink, Marlies E. J. Reinders, J.M. Boria Grinyo, Stefano Cusinato, Luisa Benozzi(Istituto di Fisiologia Clinica), Silvana Savoldi(Istituto di Fisiologia Clinica), C. Licata(Istituto di Fisiologia Clinica), Małgorzata Mizerska-Wasiak(Istituto di Fisiologia Clinica), Maria Roszkowska–Blaim(Centro de Investigación Biomédica en Red Diabetes y Enfermedades Metabólicas Asociadas), G Martina, A Messuerotti, Antonio Dal Canton(Istituto di Fisiologia Clinica), Ciro Esposito(Istituto di Fisiologia Clinica), C. Migotto(Centro de Investigación Biomédica en Red Diabetes y Enfermedades Metabólicas Asociadas), G Triolo(Istituto di Fisiologia Clinica), Filippo Mariano(Istituto di Fisiologia Clinica), Claudio Pozzi(Istituto di Fisiologia Clinica), R Boero(Centro de Investigación Biomédica en Red Diabetes y Enfermedades Metabólicas Asociadas), Gianna Mazzucco(Istituto di Fisiologia Clinica), C. Giannakakis(Istituto di Fisiologia Clinica), Eva Honsová(Uppsala University), B. Sundelin(University of Bari Aldo Moro), Anna Maria Di Palma(Istituto di Fisiologia Clinica), Franco Ferrario(Istituto di Fisiologia Clinica), Ester Gutiérrez(Istituto di Fisiologia Clinica), Anna Maria Asunis(Leicester General Hospital), Jonathan Barratt(Leicester General Hospital), Regina Tardanico(Medical University of Warsaw), Agnieszka Perkowska‐Ptasińska(Medical University of Warsaw), J. Arce Terroba(Istituto di Fisiologia Clinica), M. Fortunato, Afroditi Pantzaki(Istanbul University), Y Ozluk(Istituto di Fisiologia Clinica), E. J. Steenbergen(Istituto di Fisiologia Clinica), Magnus Söderberg(Istituto di Fisiologia Clinica), Živile Riispere(Istituto di Fisiologia Clinica), Luciana Furci(Centro de Investigación Biomédica en Red Diabetes y Enfermedades Metabólicas Asociadas), Dıclehan Orhan(Centro de Investigación Biomédica en Red Diabetes y Enfermedades Metabólicas Asociadas), David Kipgen(Centro de Investigación Biomédica en Red Diabetes y Enfermedades Metabólicas Asociadas), Donatella Casartelli(Centro de Investigación Biomédica en Red Diabetes y Enfermedades Metabólicas Asociadas), D GalesicLjubanovic, Hariklia Gakiopoulou(Istituto di Fisiologia Clinica), E. Bertoni(Hacettepe University), P. Cannata Ortiz, Henryk Karkoszka, Hermann-Josef Groene, Antonella Stoppacciaro(Istituto di Fisiologia Clinica), Ingeborg M. Bajema(Centro de Investigación Biomédica en Red Diabetes y Enfermedades Metabólicas Asociadas), J Bruijn(General University Hospital in Prague), X Fulladosa Oliveras(Centro de Investigación Biomédica en Red Diabetes y Enfermedades Metabólicas Asociadas), Jadwiga Małdyk(Istituto di Fisiologia Clinica), E. Ioachim
Cited by 109Open Access
Abstract
BACKGROUND: It is unknown whether renal pathology lesions in immunoglobulin A nephropathy (IgAN) correlate with renal outcomes over decades of follow-up. METHODS: In 1130 patients of the original Validation Study of the Oxford Classification for IgA Nephropathy (VALIGA) cohort, we studied the relationship between the MEST score (mesangial hypercellularity, M; endocapillary hypercellularity, E; segmental glomerulosclerosis, S; tubular atrophy/interstitial fibrosis, T), crescents (C) and other histological lesions with both a combined renal endpoint [50% estimated glomerular filtration rate (eGFR) loss or kidney failure] and the rate of eGFR decline over a follow-up period extending to 35 years [median 7 years (interquartile range 4.1-10.8)]. RESULTS: In this extended analysis, M1, S1 and T1-T2 lesions as well as the whole MEST score were independently related with the combined endpoint (P < 0.01), and there was no effect modification by age for these associations, suggesting that they may be valid in children and in adults as well. Only T lesions were associated with the rate of eGFR loss in the whole cohort, whereas C showed this association only in patients not treated with immunosuppression. In separate prognostic analyses, the whole set of pathology lesions provided a gain in discrimination power over the clinical variables alone, which was similar at 5 years (+2.0%) and for the whole follow-up (+1.8%). A similar benefit was observed for risk reclassification analyses (+2.7% and +2.4%). CONCLUSION: Long-term follow-up analyses of the VALIGA cohort showed that the independent relationship between kidney biopsy findings and the risk of progression towards kidney failure in IgAN remains unchanged across all age groups and decades after the renal biopsy.
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