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Diseases","doi-asserted-by":"crossref","award":["U01DK106965"],"award-info":[{"award-number":["U01DK106965"]}],"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":[[2025,7]]},"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>Higher urine levels of kidney injury molecule-1 and monocyte chemoattractant protein-1 were associated with higher risk of CKD progression.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Higher urine levels of EGF were associated with lower risk of CKD progression.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Urine kidney injury molecule-1, monocyte chemoattractant protein-1, and EGF may noninvasively assess tubule and interstitial health in diabetes and identify those at higher risk of CKD progression.<\/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>Urine biomarkers of kidney tubular health and inflammation may provide a noninvasive way to identify individuals with diabetes at higher risk for CKD progression given that the extent of tubulointerstitial pathology is related to progression of diabetic kidney disease.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We performed a case-cohort study among 898 participants in the Chronic Renal Insufficiency Cohort with diabetes and eGFR &lt;60 ml\/min per 1.73 m\n                      <jats:sup>2<\/jats:sup>\n                      . Of these individuals, the subcohort (\n                      <jats:italic toggle=\"yes\">N<\/jats:italic>\n                      =599) was randomly selected from participants with urine samples available 1 year or less after enrollment to assay for urine proteins. Cases were participants who developed CKD progression (incident ESKD, or eGFR decline of 40% or greater from baseline). The median follow-up was 7.35 years. We studied urinary biomarkers of tubulointerstitial inflammation (monocyte chemoattractant protein-1 [MCP-1]), proximal tubular injury (kidney injury molecule-1 [KIM-1]), tubular resorptive capacity (\n                      <jats:italic toggle=\"yes\">\u03b1<\/jats:italic>\n                      1-microglobulin), and tubular synthetic capacity (EGF and uromodulin). Weighted Cox regression models related urine biomarkers, standardized to urine creatinine (Cr), with CKD progression and were adjusted for CKD risk factors, including eGFR, and urine albumin-to-creatinine ratio.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>In fully adjusted models, higher urine KIM-1\/Cr was associated with higher risk of CKD progression (hazard ratio [HR], 1.16 per two-fold higher; 95% confidence interval [CI], 1.05 to 1.29) and the highest quartiles of urine KIM-1\/Cr and urine MCP-1\/Cr, compared with the lowest quartile, were associated with higher risk of CKD progression (HR, 1.71; 95% CI, 1.15 to 2.55, and HR, 1.65; 95% CI, 1.10 to 2.47, respectively). Higher urine levels of EGF\/Cr were associated with lower risk of CKD progression (HR, 0.81 per two-fold higher; 95% CI, 0.71 to 0.93), and the highest quartile of urine EGF\/Cr, compared with lowest, associated with less CKD progression (HR, 0.57; 95% CI, 0.40 to 0.81).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Urine MCP-1, KIM-1, and EGF may provide noninvasive ways to assess tubule and interstitial disease in diabetes and identify those at higher risk of CKD progression.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.2215\/cjn.0000000711","type":"journal-article","created":{"date-parts":[[2025,6,10]],"date-time":"2025-06-10T12:00:31Z","timestamp":1749556831000},"page":"958-967","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":15,"title":["Urine Biomarkers for Diabetic Kidney Disease Progression in Participants of the Chronic Renal Insufficiency Cohort Study"],"prefix":"10.2215","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2557-5161","authenticated-orcid":false,"given":"Sarah J.","family":"Schrauben","sequence":"first","affiliation":[{"name":"Department of Medicine and Biostatistics, Epidemiology and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8669-4530","authenticated-orcid":false,"given":"Xiaoming","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, Epidemiology and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dawei","family":"Xie","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, Epidemiology and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven","family":"Coca","sequence":"additional","affiliation":[{"name":"Section of Nephrology, Department of Internal Medicine, Icahn School of Medicine at Mount Sinai, New York, New York"}],"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, Clinical and Translational Research Accelerator, Yale University School of Medicine, New Haven, Connecticut"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8084-9869","authenticated-orcid":false,"given":"Joachim H.","family":"Ix","sequence":"additional","affiliation":[{"name":"Division of Nephrology-Hypertension, Department of Medicine, University of California San Diego, San Diego, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9559-204X","authenticated-orcid":false,"given":"Michael G.","family":"Shlipak","sequence":"additional","affiliation":[{"name":"Kidney Health Research Collaborative, San Francisco VA Healthcare System, University of California San Francisco, San Francisco, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8182-1238","authenticated-orcid":false,"given":"Chi-yuan","family":"Hsu","sequence":"additional","affiliation":[{"name":"Division of Nephrology, San Francisco School of Medicine, University of California San Francisco, San Francisco, California"},{"name":"Division of Research, Kaiser Permanente Northern California, Oakland, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4320-7151","authenticated-orcid":false,"given":"Jonathan 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J.","family":"Sarnak","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Tufts Medical Center, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9059-9998","authenticated-orcid":false,"given":"Mirela A.","family":"Dobre","sequence":"additional","affiliation":[{"name":"Division of Nephrology and Hypertension, University Hospitals Cleveland Medical Center, Case Western Reserve University, Cleveland, Ohio"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1325-315X","authenticated-orcid":false,"given":"Debbie","family":"Cohen","sequence":"additional","affiliation":[{"name":"Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania"}],"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":"Departments of Physiology and Biophysics and Medicine, Case Western Reserve University School of Medicine, Cleveland, Ohio"}],"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, University of Michigan, Ann Arbor, Michigan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7103-656X","authenticated-orcid":false,"given":"Mark L.","family":"Unruh","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of New Mexico School of Medicine, Albuquerque, New Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8670-3644","authenticated-orcid":false,"given":"Ana C.","family":"Ricardo","sequence":"additional","affiliation":[{"name":"Division of Nephrology, University of Illinois at Chicago, Chicago, Illinois"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sushrut","family":"Waikar","sequence":"additional","affiliation":[{"name":"Boston University Chobanian and Avedisian School of Medicine, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul L.","family":"Kimmel","sequence":"additional","affiliation":[{"name":"Department of Medicine, George Washington University, Washington, DC"}],"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 and Engineering in Medicine Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"On behalf of the CKD Biomarkers Consortium and the CRIC investigators","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2025,6,4]]},"reference":[{"issue":"12","key":"B2-20250919","doi-asserted-by":"crossref","first-page":"2032","DOI":"10.2215\/CJN.11491116","article-title":"Diabetic kidney disease: challenges, progress, and possibilities","volume":"12","author":"Alicic","year":"2017","journal-title":"Clin J Am Soc Nephrol."},{"issue":"2","key":"B3-20250919","doi-asserted-by":"crossref","first-page":"181","DOI":"10.4093\/dmj.2021.0329","article-title":"Pathophysiologic mechanisms and potential biomarkers in diabetic kidney disease","volume":"46","author":"Jung","year":"2022","journal-title":"Diabetes Metab 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