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We sought to develop and validate a tool to describe chronicity and severity of renal allograft disease and integrate it with the evaluation of disease activity.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      The training cohort included 3549 kidney transplant biopsies from an observational cohort of 937 recipients. We reweighted the chronic histologic lesions according to their time-dependent association with graft failure, and performed consensus\n                      <jats:italic toggle=\"yes\">k<\/jats:italic>\n                      -means clustering analysis. Total chronicity was calculated as the sum of the weighted chronic lesion scores, scaled to the unit interval.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      We identified four chronic clusters associated with graft outcome, based on the proportion of ambiguous clustering. The two clusters with the worst survival outcome were determined by interstitial fibrosis and tubular atrophy (IFTA) and by transplant glomerulopathy. The chronic clusters partially overlapped with the existing Banff IFTA classification (adjusted Rand index, 0.35) and were distributed independently of the acute lesions. Total chronicity strongly associated with graft failure (hazard ratio [HR], 8.33; 95% confidence interval [CI], 5.94 to 10.88;\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      &lt;0.001), independent of the total activity scores (HR, 5.01; 95% CI, 2.83 to 7.00;\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      &lt;0.001). These results were validated on an external cohort of 4031 biopsies from 2054 kidney transplant recipients.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>The evaluation of total chronicity provides information on kidney transplant pathology that complements the estimation of disease activity from acute lesion scores. Use of the data-driven algorithm used in this study, called RejectClass, may provide a holistic and quantitative assessment of kidney transplant injury phenotypes and severity.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1681\/asn.2022030290","type":"journal-article","created":{"date-parts":[[2022,9,7]],"date-time":"2022-09-07T15:10:19Z","timestamp":1662563419000},"page":"2026-2039","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":35,"title":["Data-Driven Chronic Allograft Phenotypes: A Novel and Validated Complement for Histologic Assessment of Kidney Transplant Biopsies"],"prefix":"10.1681","volume":"33","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1226-3153","authenticated-orcid":false,"given":"Thibaut","family":"Vaulet","sequence":"first","affiliation":[{"name":"ESAT Stadius Center for Dynamical Systems, Signal Processing, and Data Analytics, KU Leuven, Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3450-0033","authenticated-orcid":false,"given":"Gillian","family":"Divard","sequence":"additional","affiliation":[{"name":"Paris Translational Research Center for Organ Transplantation, Universit\u00e9 de Paris, INSERM, PARCC, Paris, France; Kidney Transplant Department, Necker Hospital, Assistance Publique\u2013H\u00f4pitaux de Paris, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3648-8963","authenticated-orcid":false,"given":"Olivier","family":"Thaunat","sequence":"additional","affiliation":[{"name":"CIRI, INSERM U1111, Universit\u00e9 Claude Bernard Lyon I, CNRS UMR5308, Ecole Normale Sup\u00e9rieure de Lyon, Univ. Lyon, Lyon, France"},{"name":"Department of Transplantation, Nephrology, and Clinical Immunology, Hospices Civils de Lyon, Edouard Herriot Hospital, Lyon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2313-5122","authenticated-orcid":false,"given":"Priyanka","family":"Koshy","sequence":"additional","affiliation":[{"name":"Department of Imaging and Pathology, University Hospitals Leuven, Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evelyne","family":"Lerut","sequence":"additional","affiliation":[{"name":"Department of Imaging and Pathology, University Hospitals Leuven, Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6196-4669","authenticated-orcid":false,"given":"Aleksandar","family":"Senev","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Immunology, and Transplantation, KU Leuven, Leuven, Belgium"},{"name":"Histocompatibility and Immunogenetics Laboratory, Belgian Red Cross\u2013Flanders, Mechelen, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6284-3757","authenticated-orcid":false,"given":"Olivier","family":"Aubert","sequence":"additional","affiliation":[{"name":"Paris Translational Research Center for Organ Transplantation, Universit\u00e9 de Paris, INSERM, PARCC, Paris, France; Kidney Transplant Department, Necker Hospital, Assistance Publique\u2013H\u00f4pitaux de Paris, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9796-9157","authenticated-orcid":false,"given":"Elisabet","family":"Van Loon","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Immunology, and Transplantation, KU Leuven, Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2235-9842","authenticated-orcid":false,"given":"Jasper","family":"Callemeyn","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Immunology, and Transplantation, KU Leuven, Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie-Paule","family":"Emonds","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Immunology, and Transplantation, KU Leuven, Leuven, Belgium"},{"name":"Histocompatibility and Immunogenetics Laboratory, Belgian Red Cross\u2013Flanders, Mechelen, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4728-9406","authenticated-orcid":false,"given":"Amaryllis","family":"Van Craenenbroeck","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Immunology, and Transplantation, KU Leuven, Leuven, Belgium"},{"name":"Department of Nephrology and Kidney Transplantation, University Hospitals Leuven, Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3096-6207","authenticated-orcid":false,"given":"Katrien","family":"De Vusser","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Immunology, and Transplantation, KU Leuven, Leuven, Belgium"},{"name":"Department of Nephrology and Kidney Transplantation, University Hospitals Leuven, Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1314-9675","authenticated-orcid":false,"given":"Ben","family":"Sprangers","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Immunology, and Transplantation, KU Leuven, Leuven, Belgium"},{"name":"Department of Nephrology and Kidney Transplantation, University Hospitals Leuven, Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maud","family":"Rabeyrin","sequence":"additional","affiliation":[{"name":"Department of Pathology, Hospices Civils de Lyon, Bron, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Val\u00e9rie","family":"Dubois","sequence":"additional","affiliation":[{"name":"Human Leukocyte Antigen (HLA) Laboratory, French National Blood Service (EFS), D\u00e9cines-Charpieu, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5546-9680","authenticated-orcid":false,"given":"Dirk","family":"Kuypers","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Immunology, and Transplantation, KU Leuven, Leuven, Belgium"},{"name":"Department of Nephrology and Kidney Transplantation, University Hospitals Leuven, Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maarten","family":"De Vos","sequence":"additional","affiliation":[{"name":"ESAT Stadius Center for Dynamical Systems, Signal Processing, and Data Analytics, KU Leuven, Leuven, Belgium"},{"name":"Department of Development and Regeneration, University Hospitals Leuven, KU Leuven, Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3388-7747","authenticated-orcid":false,"given":"Alexandre","family":"Loupy","sequence":"additional","affiliation":[{"name":"Paris Translational Research Center for Organ Transplantation, Universit\u00e9 de Paris, INSERM, PARCC, Paris, France; Kidney Transplant Department, Necker Hospital, Assistance Publique\u2013H\u00f4pitaux de Paris, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bart","family":"De Moor","sequence":"additional","affiliation":[{"name":"ESAT Stadius Center for Dynamical Systems, Signal Processing, and Data Analytics, KU Leuven, Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5625-0792","authenticated-orcid":false,"given":"Maarten","family":"Naesens","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Immunology, and Transplantation, KU Leuven, Leuven, Belgium"},{"name":"Department of Nephrology and Kidney Transplantation, University Hospitals Leuven, Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2022,11]]},"reference":[{"key":"B1-20250823","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1001\/jamasurg.2014.2038","article-title":"Survival benefit of solid-organ transplant in the United States","volume":"150","author":"Rana","year":"2015","journal-title":"JAMA Surg"},{"key":"B2-20250823","doi-asserted-by":"crossref","first-page":"918","DOI":"10.1093\/ndt\/gfab024","article-title":"Does kidney transplantation with a standard or expanded criteria donor improve patient survival? 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