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Cited by 2Renal Diseases and GlomerulopathiesChronic Kidney Disease and DiabetesRenal Transplantation Outcomes and Treatments

The DOI matches its Crossref record; 50 of the 50 references it cites were found in a registry or an index.

Individualised treatment effects of corticosteroids in IgA nephropathy

Open access
Hölscher, David L., Schmitz, Nikolas E.J., Niggemeier, Leon, Pilva, Pourya, Strauch, Martin, Tesar, Vladimir, Barratt, Jonathan, Roberts, Ian S.D., Coppo, Rosanna, Barisoni, Laura, Yanagita, Motoko, Alabalik, Ulas, Rule, Andrew D., Jagtap, Jaidip M., Abreu, Eliabe S., Seikrit, Claudia, von Stillfried, Saskia, Taal, Maarten W., Kalra, Philip A., Floege, Juergen, Kramann, Rafael, Boor, Peter, Bülow, Roman D., Russo, M.L., Troyanov, S., Cook, H.T., Roberts, I.S.D., Tesar, V., Maixnerova, D., Lundberg, S., Gesualdo, L., Emma, F., Diomedi, F., Beltrame, G., Rollino, C., Amore, A., Camilla, R., Peruzzi, L., Praga, M., Feriozzi, S., Polci, R., Segoloni, G., Colla, L., Pani, A., Piras, D., Angioi, A., Cancarini, G., Ravera, S., Durlik, M., Moggia, E., Ballarin, J., Di Giulio, S., Pugliese, F., Serriello, I., Caliskan, Y., Sever, M., Kilicaslan, I., Locatelli, F., Del Vecchio, L., Wetzels, J.F.M., Peters, H., Berg, U., Carvalho, F., da Costa Ferreira, A.C., Maggio, M., Wiecek, A., Ots-Rosenberg, M., Magistroni, R., Topaloglu, R., Bilginer, Y., D’Amico, M., Stangou, M., Giacchino, F., Goumenos, D., Kalliakmani, P., Papasotiriou, M., Galesic, K., Geddes, C., Siamopoulos, K., Balafa, O., Galliani, M., Stratta, P., Quaglia, M., Bergia, R., Cravero, R., Salvadori, M., Cirami, L., Fellstrom, B., Kloster Smerud, H., Ferrario, F., Stellato, T., Egido, J., Martin, C., Floege, J., Eitner, F., Lupo, A., Bernich, P., Menè, P., Morosetti, M., van Kooten, C., Rabelink, T., Reinders, M.E.J., Boria Grinyo, J.M., Cusinato, S., Benozzi, L., Savoldi, S., Licata, C., Mizerska-Wasiak, M., Martina, G., Messuerotti, A., Dal Canton, A., Esposito, C., Migotto, C., Triolo, G., Mariano, F., Pozzi, C., Boero, R., Bellur, S., Mazzucco, G., Giannakakis, C., Honsova, E., Sundelin, B., Di Palma, A.M., Gutiérrez, E., Asunis, A.M., Barratt, J., Tardanico, R., Perkowska-Ptasinska, A., Arce Terroba, J., Fortunato, M., Pantzaki, A., Ozluk, Y., Steenbergen, E., Soderberg, M., Riispere, Z., Furci, L., Orhan, D., Kipgen, D., Casartelli, D., Galesic Ljubanovic, D., Gakiopoulou, H., Bertoni, E., Cannata Ortiz, P., Karkoszka, H., Groene, H.J., Stoppacciaro, A., Bajema, I., Bruijn, J., Fulladosa Oliveras, X., Maldyk, J., Ioachim, E., Bavbek, N., Alpers, C., Berthoux, F., Bonsib, S., D’Agati, V., D’Amico, G., Emancipator, S., Emmal, F., Fervenza, F., Florquin, S., Fogo, A., Haas, M., Hill, P., Hogg, R., Hsu, S., Hunley, T., Hladunewich, M., Jennette, C., Joh, K., Julian, B., Kawamura, T., Lai, F., Leung, C., Li, L., Li, P., Liu, Z., Massat, A., Mackinnon, B., Mezzano, S., Schena, F., Tomino, Y., Walker, P., Wang, H., Weening, J., Yoshikawa, N., Zeng, C.H., Shi, S., Nogi, C., Suzuki, H., Koike, K., Hirano, K., Kawamura, T., Yokoo, T., Hanai, M., Fukami, K., Takahashi, K., Yuzawa, Y., Niwa, M., Yasuda, Y., Maruyama, S., Ichikawa, D., Suzuki, T., Shirai, S., Fukuda, A., Fujimoto, S., Trimarchi, H., Appel, Gerald, Babayev, Revekka, Batal, Ibrahim, Bomback, Andrew, Canetta, Pietro, Chan, Brenda, D'Agati, Vivette Denise, Dogra, Samitri, Fernandez, Hilda, Gaggero, Gabriele, Gharavi, Ali, Hines, William, Kiryluk, Krzysztof, Kudose, Satoru, Lin, Fangming, Kolupaeva, Victoria, Marasa, Maddalena, Markowitz, Glen, Navarro-Torres, Mariela, Rasouly, Hila Milo, Mohan, Sumit, Mongera, Nicola, Nestor, Jordan, Radhakrishnan, Jai, Rao, Maya, Sabatello, Maya, Sanna-Cherchi, Simone, Santoriello, Dominick, Sekulic, Miroslav, Stokes, Michael Barry, Uy, Natalie, Vena, Natalie, Wooden, Benjamin, Foroncewicz, Bartosz, Wiewiórska-Krata, Natalia, Moszczuk, Barbara, Mucha, Krzysztof, Perkowska-Ptasińska, Agnieszka, Ryszkowska, Elżbieta, Lugani, Francesca, Vellone, Valerio, Aviles, Diego, Srivastava, Tarak, Katz, Alexander, Ahn, Sun-Young, Devarajan, Prasad, Erkan, Elif, Stone, Hillarey, Mason, Sherene, Gomez-Mendez, Liliana, Greenbaum, Larry, Wang, Chia-shi, Yin, Hong (Julie), Goebel, Jens, Weaver, Donald, Krissberg, Jill, Lane, Jerome, Pan, Cindy, Cody, Ellen, Martinek-Bundt, Samantha, Carmean, Dawson, Dreher, Mary, Kallash, Mahmoud, Mahan, John, Sharpe, Samantha, Smoyer, William, Biederman, Laura, Al-Uzri, Amira, Iragorri, Sandra, Khalid, Myda, Belsha, Craig, Onugha, Elizabeth, Braun, Michael, Gomez, A.C., Vasylyeva, Tetyana, Feig, Daniel, Hannah, Melisha, Chishti, Aftab, Klein, Jon, Katsoufis, Chryso, Seeherunvong, Wacharee, Rheault, Michelle, Wong, Craig, Abid, Qassim, Barcia, John, Swiatecka-Urban, Agnes, Bartosh, Sharon, Stotter, Brian, Gaut, Joseph, Laurin, Louis-Philippe, Royal, Virginie, Latour, Mathieu, Patey, Natlie (Natacha), Achanti, Anand, Budisavljevic, Milos, Pasham, Vishwajeeth, Ghossein, Cybele, Peleg, Yonatan, Almaani, Salem, Ayoub, Isabelle, Parikh, Samir, Rovin, Brad, Satoskar, Anjali, Chang, Anthony, Fatima, Huma, Novak, Jan, Renfrow, Matthew, Rizk, Dana, Chen, Dhruti, Derebail, Vimal, Falk, Ronald, Gibson, Keisha, Glenn, Dorey, Hogan, Susan, Jain, Koyal, Jennette, J. Charles, Moreno, Vanessa, Mottl, Amy, Poulton, Caroline, Reynolds, Monica, Saha, Manish Kanti, Wyatt, Nicole E., Fogo, Agnes, Sanghani, Neil, Kidd, Jason, Muthusamy, Selvaraj, Scobell, Rebecca, Denburg, Michelle, Kogon, Amy, Meyers, Kevin, Pradhan, Madhura, Matar, Raed Bou, O'Toole, John, Sedor, John, Sethna, Christine, Vento, Suzanne, Atta, Mohamed, Bagnasco, Serena, Neu, Alicia, Sperati, John, Adler, Sharon, Dai, Tiane, Dukkipati, Ram, Kaskel, Frederick, Brathwaite, Kaye, Reidy, Kimberly, Malaga-Dieguez, Laura, Tuttle, Katherine, Lafayette, Richard, Fahmeedah, Kamal, Talley, Elizabeth, Hladunewich, Michelle, Parekh, Rulan, Avila-Casado, Carmen, Cattran, Daniel, Reich, Heather, Kutky, Meherzad, Drexler, Yelena, Fornoni, Alessia, Hodgin, Jeffrey, Oliverio, Andrea, Hogan, Jon, Holzman, Lawrence, Palmer, Matthew, Coppock, Gaia, Mortiz, Michael, Kumar, Juhi, Alpers, Charles, Jefferson, J. Ashley, Sambandam, Kamal, Roehm, Bethany, Nast, Cynthia, Hou, Jean, Barisoni, Laura, Gadegbeku, Crystal, Smith, Abigail, Gillespie, Brenda, Robinson, Bruce, Kretzler, Matthias, Modi, Zubin, Mariani, Laura, Guay-Woodford, Lisa M., Taal, Maarten W., Cockwell, Paul, Fraser, Simon D.S., Kalra, Philip A., Saleem, Moin, Wheeler, David C., Coppo, Rosanna, Barbour, Sean, Barratt, Jonathan, Roberts, Ian S.D., Floege, Juergen, Tesar, Vladimir, Bülow, Roman D., Hölscher, David L., Zhang, Hong, Wong, Muh Geot, Barisoni, Laura, Haas, Mark, Yanagita, Motoko, Kaneko, Keiichi, Koshida, Takeo, Lundberg, Sigrid·2026·eBioMedicine
DOI 10.1016/j.ebiom.2026.106396PMC PMC13377490
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Abstract

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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  1. Liu, 2022, Estimation of 24-h urine protein excretion using urine albumin-to-creatinine ratio from an in-hospital population, Med Sci Monit, 28
  2. Zhang, 2016, Multiple imputation with multivariate imputation by chained equation (MICE) package, Ann Transl Med, 4, 30

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Authors
Hölscher, D. L., Schmitz, N. E. J., Niggemeier, L., Pilva, P., Strauch, M., Tesar, V., Barratt, J., Roberts, I. S. D., Coppo, R., Barisoni, L., Yanagita, M., Alabalik, U., Rule, A. D., Jagtap, J. M., Abreu, E. S., Seikrit, C., von Stillfried, S., Taal, M. W., Kalra, P. A., Floege, J., Kramann, R., Boor, P., Bülow, R. D., Russo, M. L., Troyanov, S., Cook, H. T., Roberts, I. S. D., Tesar, V., Maixnerova, D., Lundberg, S., Gesualdo, L., Emma, F., Diomedi, F., Beltrame, G., Rollino, C., Amore, A., Camilla, R., Peruzzi, L., Praga, M., Feriozzi, S., Polci, R., Segoloni, G., Colla, L., Pani, A., Piras, D., Angioi, A., Cancarini, G., Ravera, S., Durlik, M., Moggia, E., Ballarin, J., Di Giulio, S., Pugliese, F., Serriello, I., Caliskan, Y., Sever, M., Kilicaslan, I., Locatelli, F., Del Vecchio, L., Wetzels, J. F. M., Peters, H., Berg, U., Carvalho, F., da Costa Ferreira, A. C., Maggio, M., Wiecek, A., Ots-Rosenberg, M., Magistroni, R., Topaloglu, R., Bilginer, Y., D’Amico, M., Stangou, M., Giacchino, F., Goumenos, D., Kalliakmani, P., Papasotiriou, M., Galesic, K., Geddes, C., Siamopoulos, K., Balafa, O., Galliani, M., Stratta, P., Quaglia, M., Bergia, R., Cravero, R., Salvadori, M., Cirami, L., Fellstrom, B., Kloster Smerud, H., Ferrario, F., Stellato, T., Egido, J., Martin, C., Floege, J., Eitner, F., Lupo, A., Bernich, P., Menè, P., Morosetti, M., van Kooten, C., Rabelink, T., Reinders, M. E. J., Boria Grinyo, J. M., Cusinato, S., Benozzi, L., Savoldi, S., Licata, C., Mizerska-Wasiak, M., Martina, G., Messuerotti, A., Dal Canton, A., Esposito, C., Migotto, C., Triolo, G., Mariano, F., Pozzi, C., Boero, R., Bellur, S., Mazzucco, G., Giannakakis, C., Honsova, E., Sundelin, B., Di Palma, A. M., Gutiérrez, E., Asunis, A. M., Barratt, J., Tardanico, R., Perkowska-Ptasinska, A., Arce Terroba, J., Fortunato, M., Pantzaki, A., Ozluk, Y., Steenbergen, E., Soderberg, M., Riispere, Z., Furci, L., Orhan, D., Kipgen, D., Casartelli, D., Galesic Ljubanovic, D., Gakiopoulou, H., Bertoni, E., Cannata Ortiz, P., Karkoszka, H., Groene, H. J., Stoppacciaro, A., Bajema, I., Bruijn, J., Fulladosa Oliveras, X., Maldyk, J., Ioachim, E., Bavbek, N., Alpers, C., Berthoux, F., Bonsib, S., D’Agati, V., D’Amico, G., Emancipator, S., Emmal, F., Fervenza, F., Florquin, S., Fogo, A., Haas, M., Hill, P., Hogg, R., Hsu, S., Hunley, T., Hladunewich, M., Jennette, C., Joh, K., Julian, B., Kawamura, T., Lai, F., Leung, C., Li, L., Li, P., Liu, Z., Massat, A., Mackinnon, B., Mezzano, S., Schena, F., Tomino, Y., Walker, P., Wang, H., Weening, J., Yoshikawa, N., Zeng, C. H., Shi, S., Nogi, C., Suzuki, H., Koike, K., Hirano, K., Kawamura, T., Yokoo, T., Hanai, M., Fukami, K., Takahashi, K., Yuzawa, Y., Niwa, M., Yasuda, Y., Maruyama, S., Ichikawa, D., Suzuki, T., Shirai, S., Fukuda, A., Fujimoto, S., Trimarchi, H., Appel, G., Babayev, R., Batal, I., Bomback, A., Canetta, P., Chan, B., D'Agati, V. D., Dogra, S., Fernandez, H., Gaggero, G., Gharavi, A., Hines, W., Kiryluk, K., Kudose, S., Lin, F., Kolupaeva, V., Marasa, M., Markowitz, G., Navarro-Torres, M., Rasouly, H. M., Mohan, S., Mongera, N., Nestor, J., Radhakrishnan, J., Rao, M., Sabatello, M., Sanna-Cherchi, S., Santoriello, D., Sekulic, M., Stokes, M. B., Uy, N., Vena, N., Wooden, B., Foroncewicz, B., Wiewiórska-Krata, N., Moszczuk, B., Mucha, K., Perkowska-Ptasińska, A., Ryszkowska, E., Lugani, F., Vellone, V., Aviles, D., Srivastava, T., Katz, A., Ahn, S.-Y., Devarajan, P., Erkan, E., Stone, H., Mason, S., Gomez-Mendez, L., Greenbaum, L., Wang, C.-S., Yin, H. (., Goebel, J., Weaver, D., Krissberg, J., Lane, J., Pan, C., Cody, E., Martinek-Bundt, S., Carmean, D., Dreher, M., Kallash, M., Mahan, J., Sharpe, S., Smoyer, W., Biederman, L., Al-Uzri, A., Iragorri, S., Khalid, M., Belsha, C., Onugha, E., Braun, M., Gomez, A. C., Vasylyeva, T., Feig, D., Hannah, M., Chishti, A., Klein, J., Katsoufis, C., Seeherunvong, W., Rheault, M., Wong, C., Abid, Q., Barcia, J., Swiatecka-Urban, A., Bartosh, S., Stotter, B., Gaut, J., Laurin, L.-P., Royal, V., Latour, M., Patey, N. (., Achanti, A., Budisavljevic, M., Pasham, V., Ghossein, C., Peleg, Y., Almaani, S., Ayoub, I., Parikh, S., Rovin, B., Satoskar, A., Chang, A., Fatima, H., Novak, J., Renfrow, M., Rizk, D., Chen, D., Derebail, V., Falk, R., Gibson, K., Glenn, D., Hogan, S., Jain, K., Jennette, J. C., Moreno, V., Mottl, A., Poulton, C., Reynolds, M., Saha, M. K., Wyatt, N. E., Fogo, A., Sanghani, N., Kidd, J., Muthusamy, S., Scobell, R., Denburg, M., Kogon, A., Meyers, K., Pradhan, M., Matar, R. B., O'Toole, J., Sedor, J., Sethna, C., Vento, S., Atta, M., Bagnasco, S., Neu, A., Sperati, J., Adler, S., Dai, T., Dukkipati, R., Kaskel, F., Brathwaite, K., Reidy, K., Malaga-Dieguez, L., Tuttle, K., Lafayette, R., Fahmeedah, K., Talley, E., Hladunewich, M., Parekh, R., Avila-Casado, C., Cattran, D., Reich, H., Kutky, M., Drexler, Y., Fornoni, A., Hodgin, J., Oliverio, A., Hogan, J., Holzman, L., Palmer, M., Coppock, G., Mortiz, M., Kumar, J., Alpers, C., Jefferson, J. A., Sambandam, K., Roehm, B., Nast, C., Hou, J., Barisoni, L., Gadegbeku, C., Smith, A., Gillespie, B., Robinson, B., Kretzler, M., Modi, Z., Mariani, L., Guay-Woodford, L. M., Taal, M. W., Cockwell, P., Fraser, S. D. S., Kalra, P. A., Saleem, M., Wheeler, D. C., Coppo, R., Barbour, S., Barratt, J., Roberts, I. S. D., Floege, J., Tesar, V., Bülow, R. D., Hölscher, D. L., Zhang, H., Wong, M. G., Barisoni, L., Haas, M., Yanagita, M., Kaneko, K., Koshida, T., & Lundberg, S.
Affiliations
  • Universitätsklinikum Aachen (DE)
  • Mayo Clinic (US)
  • Charles University (CZ)
  • National Health Service (GB)
Corresponding author
Boor, Peter
ORCID
Venue
eBioMedicine
Publisher
Elsevier BV
Published
2026-08
Volume
130
Pages
106396
ISSN
2352-3964 (ISSN-L)
DOI
10.1016/j.ebiom.2026.106396
PMC
PMC13377490
OpenAlex
W7168248708
Cited by
2
References
50
Citations by year
2026: 2
FWCI
8.00
Type
journal article
Language
en
Open access
Licence
Locations
  • EBioMedicine (publishedVersion, cc-by)
  • medRxiv (acceptedVersion)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Repository@Nottingham (University of Nottingham) (acceptedVersion, other-oa)
  • UNICA IRIS Institutional Research Information System (University of Cagliari) (submittedVersion, cc-by)
  • Institutional Research Information System University of Turin (University of Turin) (submittedVersion, other-oa)
  • Repository@Nottingham (University of Nottingham) (submittedVersion, cc-by)
  • Radboud Repository (Radboud University) (submittedVersion)
  • IRIS Research product catalog (Sapienza University of Rome) (submittedVersion)
  • RWTH Publications (RWTH Aachen) (submittedVersion)
  • RWTH Publications (RWTH Aachen) (submittedVersion, other-oa)
  • CINECA IRIS Institutional Research Information System (University of Bari Aldo Moro) (submittedVersion)
  • RWTH Publications (RWTH Aachen)
Funders
  • Bundesministerium für Forschung Technologie und Raumfahrt Informationstechnikzentrum Bund
  • German Research Foundation
  • RWTH Aachen University Faculty of Medicine
  • European Research Council
Topics
  • Health Sciences › Medicine › Nephrology › Renal Diseases and Glomerulopathies
  • Health Sciences › Medicine › Nephrology › Chronic Kidney Disease and Diabetes
  • Health Sciences › Medicine › Transplantation › Renal Transplantation Outcomes and Treatments
Keywords
IgA nephropathy, systemic corticosteroids, personalized treatment, causal machine learning, treatment effect heterogeneity, pathomics, renal biopsy histology, interstitial inflammation, tubulitis, glomerular filtration rate decline, renal failure, precision therapy, treatment response prediction

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