Accès ouvert déclaré 2026 article

Individualised treatment effects of corticosteroids in IgA nephropathy

David L. Hölscher, Nikolas E.J. Schmitz, Leon Niggemeier, Pourya Pilva, Martin Strauch, Vladimir Tesar, Jonathan Barratt, Ian S.D. Roberts, Rosanna Coppo, Laura Barisoni, Motoko Yanagita, Ulas Alabalik, Andrew D. Rule, Jaidip M. Jagtap, Eliabe S. Abreu, Claudia Seikrit, Saskia von Stillfried, Maarten W. Taal, Philip A. Kalra, Juergen Floege, Rafael Kramann, Peter Boor, Roman D. Bülow, M.L. Russo, S. Troyanov, H.T. Cook, I.S.D. Roberts, V. Tesar, D. Maixnerova, S. Lundberg, L. Gesualdo, F. Emma, F. Diomedi, G. Beltrame, C. Rollino, A. Amore, R. Camilla, L. Peruzzi, M. Praga, S. Feriozzi, R. Polci, G. Segoloni, L. Colla, A. Pani, D. Piras, A. Angioi, G. Cancarini, S. Ravera, M. Durlik, E. Moggia, J. Ballarin, S. Di Giulio, F. Pugliese, I. Serriello, Y. Caliskan, M. Sever, I. Kilicaslan, F. Locatelli, L. Del Vecchio, J.F.M. Wetzels, H. Peters, U. Berg, F. Carvalho, A.C. da Costa Ferreira, M. Maggio, A. Wiecek, M. Ots-Rosenberg, R. Magistroni, R. Topaloglu, Y. Bilginer, M. D’Amico, M. Stangou, F. Giacchino, D. Goumenos, P. Kalliakmani, M. Papasotiriou, K. Galesic, C. Geddes, K. Siamopoulos, O. Balafa, M. Galliani, P. Stratta, M. Quaglia, R. Bergia, R. Cravero, M. Salvadori, L. Cirami, B. Fellstrom, H. Kloster Smerud, F. Ferrario, T. Stellato, J. Egido, C. Martin, J. Floege, F. Eitner, A. Lupo, P. Bernich, P. Menè, M. Morosetti, C. van Kooten, T. Rabelink, M.E.J. Reinders, J.M. Boria Grinyo, S. Cusinato, L. Benozzi, S. Savoldi, C. Licata, M. Mizerska-Wasiak, G. Martina, A. Messuerotti, A. Dal Canton, C. Esposito, C. Migotto, G. Triolo, F. Mariano, C. Pozzi, R. Boero, S. Bellur, G. Mazzucco, C. Giannakakis, E. Honsova, B. Sundelin, A.M. Di Palma, E. Gutiérrez, A.M. Asunis, J. Barratt, R. Tardanico, A. Perkowska-Ptasinska, J. Arce Terroba, M. Fortunato, A. Pantzaki, Y. Ozluk, E. Steenbergen, M. Soderberg, Z. Riispere, L. Furci, D. Orhan, D. Kipgen, D. Casartelli, D. Galesic Ljubanovic, H. Gakiopoulou, E. Bertoni, P. Cannata Ortiz, H. Karkoszka, H.J. Groene, A. Stoppacciaro, I. Bajema, J. Bruijn, X. Fulladosa Oliveras, J. Maldyk, E. Ioachim, N. Bavbek, C. Alpers, F. Berthoux, S. Bonsib, V. D’Agati, G. D’Amico, S. Emancipator, F. Emmal, F. Fervenza, S. Florquin, A. Fogo, M. Haas, P. Hill, R. Hogg, S. Hsu, T. Hunley, M. Hladunewich, C. Jennette, K. Joh, B. Julian, T. Kawamura, F. Lai, C. Leung, L. Li, P. Li, Z. Liu, A. Massat, B. Mackinnon, S. Mezzano, F. Schena, Y. Tomino, P. Walker, H. Wang, J. Weening, N. Yoshikawa, C.H. Zeng, S. Shi, C. Nogi, H. Suzuki, K. Koike, K. Hirano, T. Yokoo, M. Hanai, K. Fukami, K. Takahashi, Y. Yuzawa, M. Niwa, Y. Yasuda, S. Maruyama, D. Ichikawa, T. Suzuki, S. Shirai, A. Fukuda, S. Fujimoto, H. Trimarchi, Gerald Appel, Revekka Babayev, Ibrahim Batal, Andrew Bomback, Pietro Canetta, Brenda Chan, Vivette Denise D'Agati, Samitri Dogra, Hilda Fernandez, Gabriele Gaggero, Ali Gharavi, William Hines, Krzysztof Kiryluk, Satoru Kudose, Fangming Lin, Victoria Kolupaeva, Maddalena Marasa, Glen Markowitz, Mariela Navarro-Torres, Hila Milo Rasouly, Sumit Mohan, Nicola Mongera, Jordan Nestor, Jai Radhakrishnan, Maya Rao, Maya Sabatello, Simone Sanna-Cherchi, Dominick Santoriello, Miroslav Sekulic, Michael Barry Stokes, Natalie Uy, Natalie Vena, Benjamin Wooden, Bartosz Foroncewicz, Natalia Wiewiórska-Krata, Barbara Moszczuk, Krzysztof Mucha, Agnieszka Perkowska-Ptasińska, Elżbieta Ryszkowska, Francesca Lugani, Valerio Vellone, Diego Aviles, Tarak Srivastava, Alexander Katz, Sun-Young Ahn, Prasad Devarajan, Elif Erkan, Hillarey Stone, Sherene Mason, Liliana Gomez-Mendez, Larry Greenbaum, Chia-shi Wang, Hong (Julie) Yin, Jens Goebel, Donald Weaver, Jill Krissberg, Jerome Lane, Cindy Pan, Ellen Cody, Samantha Martinek-Bundt, Dawson Carmean, Mary Dreher, Mahmoud Kallash, John Mahan, Samantha Sharpe, William Smoyer, Laura Biederman, Amira Al-Uzri, Sandra Iragorri, Myda Khalid, Craig Belsha, Elizabeth Onugha, Michael Braun, A.C. Gomez, Tetyana Vasylyeva, Daniel Feig, Melisha Hannah, Aftab Chishti, Jon Klein, Chryso Katsoufis, Wacharee Seeherunvong, Michelle Rheault, Craig Wong, Qassim Abid, John Barcia, Agnes Swiatecka-Urban, Sharon Bartosh, Brian Stotter, Joseph Gaut, Louis-Philippe Laurin, Virginie Royal, Mathieu Latour, Natlie (Natacha) Patey, Anand Achanti, Milos Budisavljevic, Vishwajeeth Pasham, Cybele Ghossein, Yonatan Peleg, Salem Almaani, Isabelle Ayoub, Samir Parikh, Brad Rovin, Anjali Satoskar, Anthony Chang, Huma Fatima, Jan Novak, Matthew Renfrow, Dana Rizk, Dhruti Chen, Vimal Derebail, Ronald Falk, Keisha Gibson, Dorey Glenn, Susan Hogan, Koyal Jain, J. Charles Jennette, Vanessa Moreno, Amy Mottl, Caroline Poulton, Monica Reynolds, Manish Kanti Saha, Nicole E. Wyatt, Agnes Fogo, Neil Sanghani, Jason Kidd, Selvaraj Muthusamy, Rebecca Scobell, Michelle Denburg, Amy Kogon, Kevin Meyers, Madhura Pradhan, Raed Bou Matar, John O'Toole, John Sedor, Christine Sethna, Suzanne Vento, Mohamed Atta, Serena Bagnasco, Alicia Neu, John Sperati, Sharon Adler, Tiane Dai, Ram Dukkipati, Frederick Kaskel, Kaye Brathwaite, Kimberly Reidy, Laura Malaga-Dieguez, Katherine Tuttle, Richard Lafayette, Kamal Fahmeedah, Elizabeth Talley, Michelle Hladunewich, Rulan Parekh, Carmen Avila-Casado, Daniel Cattran, Heather Reich, Meherzad Kutky, Yelena Drexler, Alessia Fornoni, Jeffrey Hodgin, Andrea Oliverio, Jon Hogan, Lawrence Holzman, Matthew Palmer, Gaia Coppock, Michael Mortiz, Juhi Kumar, Charles Alpers, J. Ashley Jefferson, Kamal Sambandam, Bethany Roehm, Cynthia Nast, Jean Hou, Crystal Gadegbeku, Abigail Smith, Brenda Gillespie, Bruce Robinson, Matthias Kretzler, Zubin Modi, Laura Mariani, Lisa M. Guay-Woodford, Paul Cockwell, Simon D.S. Fraser, Moin Saleem, David C. Wheeler, Sean Barbour, Hong Zhang, Muh Geot Wong, Mark Haas, Keiichi Kaneko, Takeo Koshida, Sigrid Lundberg

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Le résumé fourni par la source

BACKGROUND: IgA nephropathy (IgAN) has diverse clinical presentations and responses to treatment. For systemic corticosteroids in particular, randomised controlled trials have reported conflicting effects, highlighting the need for individualised treatment strategies. METHODS: In this retrospective cohort study, we derived and validated a causal machine learning (ML) framework to estimate individualised corticosteroid treatment effects in IgAN. Eight international cohorts, including the VALIGA, CureGN, and NURTuRE-CKD repositories, comprising 1022 patients, were analysed (derivation, n = 464; validation, n = 558). We integrated baseline clinical data, histopathological classification scores (MEST-C), and deep learning-based histomorphological biomarkers (pathomics) from digitised kidney biopsies. The framework estimated the effect of systemic corticosteroids on the composite endpoint of a ≥50% decline in estimated glomerular filtration rate or kidney failure within five years of biopsy. FINDINGS: Across the overall study population, systemic corticosteroid therapy was not associated with a significant improvement in the composite outcome (p = 0·27). However, the causal ML framework revealed substantial treatment heterogeneity, identifying patients with high predicted benefit who achieved longer progression-free survival with corticosteroids (0·43 years, 95% CI 0·18-0·73, p < 0·01), while no benefit was observed in those with low predicted benefit (-0·005 years, 95% CI -0·3 to 0·22, p > 0·05). An individualised framework-guided treatment assignment was estimated to reduce systemic corticosteroid use by 60·7%. Pathomics facilitated the identification of interstitial inflammation and tubulitis as key features of corticosteroid response. INTERPRETATION: This study demonstrates that a causal ML framework integrating clinical, histopathological, and pathomics predictors can individualise treatment assignments for systemic corticosteroids in IgAN. This approach provides a blueprint for precision therapy in IgAN, supporting AI-enhanced clinical decision-making in the era of emerging targeted treatments. FUNDING: German Research Foundation; European Research Council; German Federal Ministry of Education and Research; German Innovation Fund of the Federal Joint Committee; Clinician Scientist Program of the Faculty of Medicine RWTH Aachen University.

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DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.

Titre Crossref: Individualised treatment effects of corticosteroids in IgA nephropathy
Date Crossref: 01/08/2026
Éditeur: Elsevier BV
Type: journal-article

Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.

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RWTH Aachen University Institute of Pathology pays non établi dans la notice
Université ou école supérieure
Universitätsklinikum Aachen pays non établi dans la notice
Établissement de santé
Charles University Department of Nephrology pays non établi dans la notice
Université ou école supérieure
Leicester General Hospital pays non établi dans la notice
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University Hospitals of Leicester NHS Trust pays non établi dans la notice
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National Health Service John Walls Renal Unit pays non établi dans la notice
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University of Oxford pays non établi dans la notice
Université ou école supérieure
Fondazione Ricerca Molinette pays non établi dans la notice
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Ospedale Regina Margherita pays non établi dans la notice
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Duke University Department of Pathology pays non établi dans la notice
Université ou école supérieure
Kyoto University pays non établi dans la notice
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Dicle University pays non établi dans la notice
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Institute of Pathology — RWTH Aachen University, Universitätsklinikum Aachen et Department of Nephrology — Charles University, avec 9 autres affiliations.

Une affiliation ne permet pas de déduire la nationalité d’un auteur.

Les sujets associés

Renal Diseases and GlomerulopathiesRenal Transplantation Outcomes and TreatmentsSystemic Lupus Erythematosus Research

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