{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T14:50:23Z","timestamp":1786373423526,"version":"build-2736575974"},"reference-count":35,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"5","funder":[{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"crossref","award":["5U01DK102730"],"award-info":[{"award-number":["5U01DK102730"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"crossref","award":["5 TL1 DK 139565-2"],"award-info":[{"award-number":["5 TL1 DK 139565-2"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["CJASN"],"published-print":{"date-parts":[[2025,5]]},"abstract":"<jats:sec>\n                    <jats:title>Key Points<\/jats:title>\n                    <jats:p>\n                      <jats:list list-type=\"bullet\">\n                        <jats:list-item>\n                          <jats:p>We identified three kidney health dimensions using 17 urine and plasma biomarkers across two cohorts of persons with diabetes and CKD.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Worse scores for tubule injury, tubule function, and systemic inflammation\/filtration were associated with a higher risk of CKD progression and death.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>A multibiomarker approach could help capture tubulointerstitial health in persons with diabetes and CKD.<\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Individual kidney tubule biomarkers are associated with risks of CKD progression and mortality in persons with diabetes. Integrating multiple kidney biomarkers using a latent variable method of exploratory factor analysis could define distinct dimensions of kidney health and their associations with adverse outcomes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We conducted a factor analysis of 17 candidate urine and plasma biomarkers in 1256 participants with diabetes and eGFR &lt;60 ml\/min per 1.73 m\n                      <jats:sup>2<\/jats:sup>\n                      from the Chronic Renal Insufficiency Cohort (CRIC;\n                      <jats:italic toggle=\"yes\">N<\/jats:italic>\n                      =701) and the REasons for Geographic And Racial Differences in Stroke (REGARDS;\n                      <jats:italic toggle=\"yes\">N<\/jats:italic>\n                      =555) studies. We used Cox proportional hazards models to evaluate the associations of identified factors with CKD progression and mortality, adjusting for baseline clinical risk factors, eGFR, and albuminuria.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Three factor scores comprising ten biomarkers were identified:\n                      <jats:italic toggle=\"yes\">systemic inflammation and filtration<\/jats:italic>\n                      (plasma TNF receptor-1 and TNF receptor-2, plasma soluble urokinase plasminogen activator receptor, and plasma symmetric dimethylarginine),\n                      <jats:italic toggle=\"yes\">tubular function<\/jats:italic>\n                      (urine EGF, urine asymmetric dimethylarginine, and urine symmetric dimethylarginine), and\n                      <jats:italic toggle=\"yes\">tubular damage<\/jats:italic>\n                      (urine\n                      <jats:italic toggle=\"yes\">\u03b1<\/jats:italic>\n                      -1 microglobulin, urine kidney injury molecule-1, and urine monocyte chemoattractant protein-1). In CRIC, there were 244 incident ESKD events, 102 with \u226540% eGFR decline from baseline, and 259 deaths; in REGARDS, there were 121 incident ESKD events and 462 deaths. In CRIC, lower\n                      <jats:italic toggle=\"yes\">tubular function<\/jats:italic>\n                      (hazard ratio per 1-SD, 0.36; 95% confidence interval, 0.25 to 0.52) and higher\n                      <jats:italic toggle=\"yes\">tubular damage<\/jats:italic>\n                      (1.45; 1.18 to 1.78) scores were independently associated with higher CKD progression risk. Associations in REGARDS were weaker but directionally consistent (\n                      <jats:italic toggle=\"yes\">tubular function<\/jats:italic>\n                      score [0.81; 0.47 to 1.39] and\n                      <jats:italic toggle=\"yes\">tubular damage<\/jats:italic>\n                      score [1.12; 0.73 to 1.72]). Higher\n                      <jats:italic toggle=\"yes\">tubular damage<\/jats:italic>\n                      (1.47; 1.15 to 1.87) scores were associated with higher mortality risk in CRIC, but not REGARDS (1.15; 0.96 to 1.38). Higher\n                      <jats:italic toggle=\"yes\">systemic inflammation and filtration<\/jats:italic>\n                      factor scores were associated with higher mortality risk in both cohorts (CRIC: 1.35; 1.07 to 1.71; REGARDS: 1.41; 1.20 to 1.65).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Three distinct kidney health dimensions were identified, and each associated with CKD progression and\/or all-cause mortality in persons with diabetes and CKD.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.2215\/cjn.0000000676","type":"journal-article","created":{"date-parts":[[2025,3,14]],"date-time":"2025-03-14T12:00:46Z","timestamp":1741953646000},"page":"665-675","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":5,"title":["Defining Kidney Health Dimensions and Their Associations with Adverse Outcomes in Persons with Diabetes and CKD"],"prefix":"10.2215","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3228-483X","authenticated-orcid":false,"given":"Vanessa-Giselle","family":"Peschard","sequence":"first","affiliation":[{"name":"Division of Nephrology, Department of Medicine, University of California, San Francisco, San Francisco, California"},{"name":"Kidney Health Research Collaborative, San Francisco Veterans Affairs Health Care System, University of California, San Francisco, San Francisco, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca","family":"Scherzer","sequence":"additional","affiliation":[{"name":"Kidney Health Research Collaborative, San Francisco Veterans Affairs Health Care System, University of California, San Francisco, San Francisco, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8902-9576","authenticated-orcid":false,"given":"Michelle M.","family":"Estrella","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Medicine, University of California, San Francisco, San Francisco, California"},{"name":"Kidney Health Research Collaborative, San Francisco Veterans Affairs Health Care System, University of California, San Francisco, San Francisco, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1860-6302","authenticated-orcid":false,"given":"Mark J.","family":"Sarnak","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Medicine, Tufts Medical Center, Boston, Washington"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3465-4208","authenticated-orcid":false,"given":"Simon B.","family":"Ascher","sequence":"additional","affiliation":[{"name":"Kidney Health Research Collaborative, San Francisco Veterans Affairs Health Care System, University of California, San Francisco, San Francisco, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6580-4080","authenticated-orcid":false,"given":"James","family":"Lash","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Medicine, University of Illinois Chicago, Chicago, Illinois"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7144-386X","authenticated-orcid":false,"given":"Joseph V.","family":"Bonventre","sequence":"additional","affiliation":[{"name":"Division of Renal Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Washington"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5874-1109","authenticated-orcid":false,"given":"Jason H.","family":"Greenberg","sequence":"additional","affiliation":[{"name":"Section of Nephrology, Department of Pediatrics, Yale University School of Medicine, New Haven, Connecticut"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6593-3571","authenticated-orcid":false,"given":"Orlando M.","family":"Gutierrez","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, University of Alabama at Birmingham, Birmingham, Alabama"},{"name":"Division of Nephrology, Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3503-2208","authenticated-orcid":false,"given":"Jeffrey R.","family":"Schelling","sequence":"additional","affiliation":[{"name":"Department of Physiology and Biophysics and Medicine, Case Western Reserve University, Cleveland, Ohio"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7723-7469","authenticated-orcid":false,"given":"Ronit","family":"Katz","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, University of Washington School of Public Health, Seattle, Washington"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2282-4778","authenticated-orcid":false,"given":"Katharine L.","family":"Cheung","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Medicine, Larner College of Medicine, The University of Vermont, Burlington, Vermont"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5429-3852","authenticated-orcid":false,"given":"Emily B.","family":"Levitan","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, University of Alabama at Birmingham, Birmingham, Alabama"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2557-5161","authenticated-orcid":false,"given":"Sarah J.","family":"Schrauben","sequence":"additional","affiliation":[{"name":"Center for Clinical Epidemiology and Biostatistics, Department of Biostatistics, Epidemiology, and Informatics, Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7871-6143","authenticated-orcid":false,"given":"Mary","family":"Cushman","sequence":"additional","affiliation":[{"name":"Department of Medicine, Larner College of Medicine at the University of Vermont, Burlington, Vermont"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7457-0618","authenticated-orcid":false,"given":"Titilayo O.","family":"Ilori","sequence":"additional","affiliation":[{"name":"Nephrology Division, Boston University School of Medicine, Boston Medical Center, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9051-7385","authenticated-orcid":false,"given":"Chirag R.","family":"Parikh","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul L.","family":"Kimmel","sequence":"additional","affiliation":[{"name":"National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4699-5395","authenticated-orcid":false,"given":"Panduranga S.","family":"Rao","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Medicine, University of Michigan, Ann Arbor, Michigan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4320-7151","authenticated-orcid":false,"given":"Jonathan J.","family":"Taliercio","sequence":"additional","affiliation":[{"name":"Department of Kidney Medicine; Medical Subspecialty Institute, Cleveland Clinic, Cleveland, Ohio"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9538-9682","authenticated-orcid":false,"given":"James","family":"Sondheimer","sequence":"additional","affiliation":[{"name":"Division of Nephrology and Hypertension, Department of Medicine, Wayne State University School of Medicine, Detroit, 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