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We tested tubular biomarker associations with DKD development in type 1 diabetes (T1D).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESEARCH DESIGN AND METHODS<\/jats:title>\n                    <jats:p>We performed a case-cohort study examining associations of tubular biomarkers, measured across seven time points spanning \u223c30 years, with incident macroalbuminuria (\u201cseverely elevated albuminuria,\u201d urinary albumin excretion rate [AER] \u2265300 mg\/day) and sustained low estimated glomerular filtration rate (eGFR) (persistent eGFR &amp;lt;60 mL\/min\/1.73 m2) in the Diabetes Control and Complications Trial (DCCT)\/Epidemiology of Diabetes Interventions and Complications (EDIC) study. Biomarkers included KIM-1 and sTNFR1 in serum\/plasma, MCP-1 and EGF in urine, and a composite tubular secretion score reflecting secreted solute clearance. We assessed biomarkers using single values, as mean values from consecutive time points, and as change over consecutive time points, each as time-updated exposures.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>At baseline, mean diabetes duration was 5.9 years, with mean HbA1c 8.9%, eGFR 125 mL\/min\/1.73 m2, and AER 16 mg\/day. There were 4.8 and 3.5 cases per 1,000 person-years of macroalbuminuria and low eGFR, respectively. Assessed according to single biomarker values, KIM-1 was associated with risk of subsequent macroalbuminuria and low eGFR (hazard ratio [HR] per 20% higher biomarker 1.11 [95% CI 1.06, 1.16] and 1.12 [1.04, 1.21], respectively) and sTNFR1 was associated with subsequent macroalbuminuria (1.14 [1.03, 1.25]). Mean KIM-1 and EGF\u2013to\u2013MCP-1 ratio were associated with subsequent low eGFR. In slope analyses, increases in KIM-1 and sTNFR1 were associated with subsequent macroalbuminuria (per 20% biomarker increase, HR 1.81 [1.40, 2.34] and 1.95 [1.18, 3.21]) and low eGFR (2.26 [1.65, 3.09] and 2.94 [1.39, 6.23]).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSIONS<\/jats:title>\n                    <jats:p>Serial KIM-1 and sTNFR1 are associated with incident macroalbuminuria and sustained low eGFR in T1D.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.2337\/dc23-2196","type":"journal-article","created":{"date-parts":[[2024,3,14]],"date-time":"2024-03-14T17:07:35Z","timestamp":1710436055000},"page":"1539-1547","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":18,"title":["Associations of Kidney Tubular Biomarkers With Incident Macroalbuminuria and Sustained Low eGFR in DCCT\/EDIC"],"prefix":"10.2337","volume":"47","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9162-7428","authenticated-orcid":false,"given":"Christine P.","family":"Limonte","sequence":"first","affiliation":[{"name":"1Division of Nephrology, Department of Medicine, University of Washington, Seattle, WA"},{"name":"2Kidney Research Institute, University of Washington, Seattle, WA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyu","family":"Gao","sequence":"additional","affiliation":[{"name":"3Biostatistics Center, The George Washington University, Rockville, MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ionut","family":"Bebu","sequence":"additional","affiliation":[{"name":"3Biostatistics Center, The George Washington University, Rockville, MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jesse C.","family":"Seegmiller","sequence":"additional","affiliation":[{"name":"4Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy B.","family":"Karger","sequence":"additional","affiliation":[{"name":"4Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gayle M.","family":"Lorenzi","sequence":"additional","affiliation":[{"name":"5Department of Medicine, University of California, San Diego, La Jolla, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8492-3587","authenticated-orcid":false,"given":"Mark","family":"Molitch","sequence":"additional","affiliation":[{"name":"6Northwestern University, Chicago, IL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harsha","family":"Karanchi","sequence":"additional","affiliation":[{"name":"7Department of Medicine, Medical University of South Carolina, Charleston, SC"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruce A.","family":"Perkins","sequence":"additional","affiliation":[{"name":"8Division of Endocrinology, Department of Medicine, University of Toronto, Toronto, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ian H.","family":"de Boer","sequence":"additional","affiliation":[{"name":"1Division of Nephrology, Department of Medicine, University of Washington, Seattle, WA"},{"name":"2Kidney Research Institute, University of Washington, Seattle, WA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"DCCT","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"EDIC Research Group","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1167","published-online":{"date-parts":[[2024,3,14]]},"reference":[{"key":"2024082720361171900_B1","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"},{"key":"2024082720361171900_B2","doi-asserted-by":"crossref","first-page":"389","DOI":"10.2337\/dci17-0047","article-title":"Are all patients with type 1 diabetes destined for dialysis if they live long enough? 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