{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,9]],"date-time":"2026-04-09T20:18:48Z","timestamp":1775765928271,"version":"3.50.1"},"reference-count":62,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2026,3,13]],"date-time":"2026-03-13T00:00:00Z","timestamp":1773360000000},"content-version":"vor","delay-in-days":9,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Astra-Zeneca"},{"name":"Marie Sk\u0142odowska-Curie grant","award":["812699"],"award-info":[{"award-number":["812699"]}]},{"name":"RHU Fight-HF","award":["ANR-15-RHUS-0004"],"award-info":[{"award-number":["ANR-15-RHUS-0004"]}]},{"name":"RHU Fight-HF","award":["ANR-15-IDEX-04-LUE"],"award-info":[{"award-number":["ANR-15-IDEX-04-LUE"]}]},{"name":"French Government","award":["ANR-16-RHUS-0003"],"award-info":[{"award-number":["ANR-16-RHUS-0003"]}]},{"DOI":"10.13039\/501100003100","name":"F\u00e9d\u00e9ration Fran\u00e7aise de Cardiologie","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003100","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,3,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>Cardiovascular (CV) trials have yielded neutral results in haemodialysis. A better understanding of patient profiles is needed to personalize treatment strategies in order to improve CV outcomes in this setting. This study sought to identify biological phenotypes based on proteomic data using machine learning approaches in patients undergoing haemodialysis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and results<\/jats:title>\n                    <jats:p>A clustering analysis using 253 plasma protein biomarkers was performed in 382 patients (machine learning derivation analysis) from the AURORA trial, which tested the effect of rosuvastatin on CV outcomes in patients on haemodialysis. A decision tree was subsequently constructed to predict cluster membership and assess its association with CV outcomes in another subset of the trial (n = 389 patients, validation analysis). Four phenotypes were identified, namely \u2018cytokine storm signalling\u2019, \u2018toll-like receptors (TLRs) signalling\u2019, \u2018multiple pathways related to inflammation and fibrosis\u2019 phenotypes, as well as a \u2018reference phenotype\u2019 which exhibited the least biological abnormalities. In multivariable analysis of the validation study, after adjusting for key prognostic factors, the TLRs phenotype was significantly associated with CV death, all-cause mortality, and MACE (HR = 1.65 [1.13\u20132.41], 1.43 [1.03\u20131.98], and 1.48 [1.04\u20132.10], respectively).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Using unsupervised machine learning on proteomic data, we identified four mechanistic biological phenotypes involving cytokine storm and TLRs signalling, inflammation and fibrosis. These biological phenotypes may contribute to CV prognosis and pave the way for personalized therapy in haemodialysis.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/ehjdh\/ztag044","type":"journal-article","created":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T12:33:41Z","timestamp":1772973221000},"source":"Crossref","is-referenced-by-count":0,"title":["Proteomic phenotyping with machine learning for cardiovascular outcomes in haemodialysis: insights from the AURORA trial"],"prefix":"10.1093","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4781-0700","authenticated-orcid":false,"given":"Madonna","family":"Salib","sequence":"first","affiliation":[{"name":"Inserm, Centre d\u2019Investigations Cliniques-1433, and Inserm U1116, CHRU Nancy, F-CRIN INI-CRCT, Universit\u00e9 de Lorraine , 54500 Vandoeuvre-Les-Nancy 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,","place":["France"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6083-8946","authenticated-orcid":false,"given":"Winfried","family":"M\u00e4rz","sequence":"additional","affiliation":[{"name":"Medical Clinic V (Nephrology, Hypertensiology, Rheumatology, Endocrinology, and Diabetology), Medical Faculty Mannheim, University of Heidelberg , Theodor-Kutzer-Ufer 1-3, Mannheim ,","place":["Germany"]},{"name":"Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz , Graz ,","place":["Austria"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2750-006X","authenticated-orcid":false,"given":"Hubert","family":"Scharnagl","sequence":"additional","affiliation":[{"name":"Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz , Graz ,","place":["Austria"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ziad A","family":"Massy","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Ambroise Par\u00e9 University Hospital, APHP , Boulogne Billancourt, Paris ,","place":["France"]},{"name":"INSERM U-1018, Centre de recherche en \u00e9pid\u00e9miologie et sant\u00e9 des populations (CESP), Equipe 5 , Villejuif ,","place":["France"]},{"name":"Paris-Saclay University (PSU), University of Paris Ouest-Versailles-Saint-Quentin-en-Yvelines (UVSQ), and FCRIN INI-CRCT , Villejuif ,","place":["France"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Celine","family":"Leroy","sequence":"additional","affiliation":[{"name":"Inserm, Centre d\u2019Investigations Cliniques-1433, and Inserm U1116, CHRU Nancy, F-CRIN INI-CRCT, Universit\u00e9 de Lorraine , 54500 Vandoeuvre-Les-Nancy ,","place":["France"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kevin","family":"Duarte","sequence":"additional","affiliation":[{"name":"Inserm, Centre d\u2019Investigations Cliniques-1433, and Inserm U1116, CHRU Nancy, F-CRIN INI-CRCT, Universit\u00e9 de Lorraine , 54500 Vandoeuvre-Les-Nancy ,","place":["France"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5650-3155","authenticated-orcid":false,"given":"Emmanuel","family":"Bresso","sequence":"additional","affiliation":[{"name":"Inserm, Centre d\u2019Investigations Cliniques-1433, and Inserm U1116, CHRU Nancy, F-CRIN INI-CRCT, Universit\u00e9 de Lorraine , 54500 Vandoeuvre-Les-Nancy ,","place":["France"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-4520-4810","authenticated-orcid":false,"given":"Claire","family":"Lacomblez","sequence":"additional","affiliation":[{"name":"Inserm, Centre d\u2019Investigations Cliniques-1433, and Inserm U1116, CHRU Nancy, F-CRIN INI-CRCT, Universit\u00e9 de Lorraine , 54500 Vandoeuvre-Les-Nancy 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Navarra, Universidad P\u00fablica de Navarra (UPNA), IdiSNA , Pamplona ,","place":["Spain"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4470-7932","authenticated-orcid":false,"given":"Patrick","family":"Rossignol","sequence":"additional","affiliation":[{"name":"Inserm, Centre d\u2019Investigations Cliniques-1433, and Inserm U1116, CHRU Nancy, F-CRIN INI-CRCT, Universit\u00e9 de Lorraine , 54500 Vandoeuvre-Les-Nancy ,","place":["France"]},{"name":"Medical Specialties-Nephrology-Hemodialysis Departments, Princess Grace Hospital, and Private Hemodialysis Centre , Monaco ,","place":["Monaco"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7456-1570","authenticated-orcid":false,"given":"Faiez","family":"Zannad","sequence":"additional","affiliation":[{"name":"Inserm, Centre d\u2019Investigations Cliniques-1433, and Inserm U1116, CHRU Nancy, F-CRIN INI-CRCT, Universit\u00e9 de Lorraine , 54500 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