{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T16:28:17Z","timestamp":1791044897498,"version":"4.1.0"},"reference-count":32,"publisher":"Public Library of Science (PLoS)","issue":"6","license":[{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["R01-DK128803"],"award-info":[{"award-number":["R01-DK128803"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["U01-NS041588"],"award-info":[{"award-number":["U01-NS041588"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["U01-NS041588"],"award-info":[{"award-number":["U01-NS041588"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000009","name":"Foundation for the National Institutes of Health","doi-asserted-by":"publisher","award":["U01-NS041588"],"award-info":[{"award-number":["U01-NS041588"]}],"id":[{"id":"10.13039\/100000009","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["U01-NS041588"],"award-info":[{"award-number":["U01-NS041588"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["R01-HL80477"],"award-info":[{"award-number":["R01-HL80477"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["R01-HL165452"],"award-info":[{"award-number":["R01-HL165452"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["R37-DK39733"],"award-info":[{"award-number":["R37-DK39733"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["R01-DK072381"],"award-info":[{"award-number":["R01-DK072381"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["U01-DK085660"],"award-info":[{"award-number":["U01-DK085660"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:sec id=\"sec001\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Approximately one in five patients undergoing coronary artery bypass graft (CABG) surgery will develop post-operative acute kidney injury (AKI). We sought to determine whether biomarkers of kidney tubule dysfunction and injury are associated with long-term risk of acute kidney injury (AKI) after coronary artery bypass graft (CABG) surgery.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec002\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We performed a cohort study using data from the REasons for Geographic And Racial Differences in Stroke (REGARDS), a national, population-based, longitudinal cohort study of 30,239 U.S. adults aged \u226545 years. Of 760 REGARDS participants who underwent CABG surgery after their REGARDS baseline visit, we excluded those with a history of dialysis or kidney transplant, missing laboratory data or with illegible or erroneous records, leaving 394 in the analysis. Exposures included urinary biomarkers of kidney tubule dysfunction (urine alpha-1 microglobulin [A1M], uromodulin [UMOD] and epidermal growth factor [EGF]) and injury (kidney injury molecule-1 [KIM-1]), measured at an average of 5.5 years before CABG surgery. The primary outcome was AKI development following CABG surgery, defined as an increase in serum creatinine \u22650.3\u2009mg\/dL from 48 hours prior to CABG surgery to end of hospitalization.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec003\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Of 394 participants, 176 (45%) experienced post-CABG surgery AKI. Higher baseline urine A1M was associated with higher odds of AKI (adjusted OR 1.34 per 2-fold higher A1M, 95% Confidence Interval (CI): 1.00\u20131.80). Higher urine UMOD was associated with lower odds of AKI (adjusted OR 0.77 per 2-fold higher UMOD, 95% CI 0.62\u20130.95). Higher EGF showed a tendency towards lower odds of AKI (adjusted OR 0.79 per 2-fold higher EGF, 95% CI 0.59\u20131.05). KIM-1 was not associated with AKI (adjusted OR 0.92 per 2-fold higher KIM-1, 95% CI 0.77\u20131.10).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec004\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Select biomarkers of kidney tubule dysfunction, but not injury, are associated with future risk of AKI after CABG surgery. Biomarkers measured years before surgery may predict post-CABG surgery AKI.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1371\/journal.pone.0331996","type":"journal-article","created":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T17:55:03Z","timestamp":1780336503000},"page":"e0331996","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":1,"title":["Markers of kidney tubule dysfunction and injury and long-term risk of acute kidney injury following coronary artery bypass graft surgery"],"prefix":"10.1371","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-0692-9967","authenticated-orcid":true,"given":"Lauren","family":"Shingler","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashutosh","family":"Tamhane","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-3737-3041","authenticated-orcid":true,"given":"Ching-Min","family":"Chu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer A.","family":"Frey","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily B.","family":"Levitan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suzanne E.","family":"Judd","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander L.","family":"Bullen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edward D.","family":"Siew","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph V.","family":"Bonventre","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael G.","family":"Shlipak","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Byron","family":"Jaeger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2542-6502","authenticated-orcid":true,"given":"Jesse C.","family":"Seegmiller","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"Keister","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Orlando M.","family":"Gutierrez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joachim H.","family":"Ix","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4738-0093","authenticated-orcid":true,"given":"Henry E.","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2026,6,1]]},"reference":[{"issue":"3","key":"pone.0331996.ref001","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1038\/ki.2013.153","article-title":"Raising awareness of acute kidney injury: a global perspective of a silent killer","volume":"84","author":"AJP Lewington","year":"2013","journal-title":"Kidney Int"},{"issue":"6","key":"pone.0331996.ref002","doi-asserted-by":"crossref","first-page":"961","DOI":"10.1053\/j.ajkd.2008.11.034","article-title":"Long-term risk of mortality and other adverse outcomes after acute kidney injury: a systematic review and meta-analysis","volume":"53","author":"SG Coca","year":"2009","journal-title":"Am J Kidney Dis"},{"issue":"6","key":"pone.0331996.ref003","doi-asserted-by":"crossref","first-page":"880","DOI":"10.1097\/ALN.0000000000004734","article-title":"Acute kidney injury after cardiac surgery: prediction, prevention, and management","volume":"139","author":"SR Cheruku","year":"2023","journal-title":"Anesthesiology"},{"issue":"22","key":"pone.0331996.ref004","doi-asserted-by":"crossref","first-page":"5285","DOI":"10.3390\/jcm10225285","article-title":"Cardiac surgery associated AKI prevention strategies and medical treatment for CSA-AKI","volume":"10","author":"M Ostermann","year":"2021","journal-title":"J Clin Med"},{"issue":"1","key":"pone.0331996.ref005","doi-asserted-by":"crossref","first-page":"598","DOI":"10.1186\/s13019-024-03103-0","article-title":"Factors associated with acute kidney injury after on-pump coronary artery bypass grafting","volume":"19","author":"S Maruniak","year":"2024","journal-title":"J Cardiothorac Surg"},{"issue":"5","key":"pone.0331996.ref006","doi-asserted-by":"crossref","first-page":"719","DOI":"10.1053\/j.ajkd.2021.03.026","article-title":"The promise of tubule biomarkers in kidney disease: a review","volume":"78","author":"JH Ix","year":"2021","journal-title":"American J Kidney Diseases: The Official Journal of the National Kidney Foundation"},{"issue":"1","key":"pone.0331996.ref007","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S0272-6386(12)80312-X","article-title":"Tubulointerstitial changes as a major determinant in the progression of renal damage","volume":"20","author":"KA Nath","year":"1992","journal-title":"Am J Kidney Dis"},{"issue":"9","key":"pone.0331996.ref008","doi-asserted-by":"crossref","first-page":"561","DOI":"10.7326\/0003-4819-152-9-201005040-00006","article-title":"The association between age and nephrosclerosis on renal biopsy among healthy adults","volume":"152","author":"AD Rule","year":"2010","journal-title":"Ann Intern Med"},{"issue":"4","key":"pone.0331996.ref009","doi-asserted-by":"crossref","first-page":"1046","DOI":"10.3390\/biomedicines11041046","article-title":"Novel biomarkers for early detection of acute kidney injury and prediction of long-term kidney function decline after partial nephrectomy","volume":"11","author":"M Allinovi","year":"2023","journal-title":"Biomedicines"},{"issue":"8","key":"pone.0331996.ref010","doi-asserted-by":"crossref","first-page":"673","DOI":"10.1159\/000518240","article-title":"Urine alpha-1-microglobulin levels and acute kidney injury, mortality, and cardiovascular events following cardiac surgery","volume":"52","author":"JG Amatruda","year":"2021","journal-title":"Am J Nephrol"},{"issue":"1","key":"pone.0331996.ref011","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1038\/s41392-020-0106-1","article-title":"Potential targeted therapy and diagnosis based on novel insight into growth factors, receptors, and downstream effectors in acute kidney injury and acute kidney injury-chronic kidney disease progression","volume":"5","author":"L Gao","year":"2020","journal-title":"Signal Transduct Target Ther"},{"issue":"3","key":"pone.0331996.ref012","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1159\/000086678","article-title":"The reasons for geographic and racial differences in stroke study: objectives and design","volume":"25","author":"VJ Howard","year":"2005","journal-title":"Neuroepidemiology"},{"issue":"3","key":"pone.0331996.ref013","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1159\/000441505","article-title":"Prehospitalization risk factors for acute kidney injury during hospitalization for serious infections in the REGARDS cohort","volume":"5","author":"HE Wang","year":"2015","journal-title":"Nephron Extra"},{"key":"pone.0331996.ref014","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1186\/2193-1801-3-207","article-title":"Association of inflammatory and endothelial cell activation biomarkers with acute kidney injury after sepsis","volume":"3","author":"TC Powell","year":"2014","journal-title":"Springerplus"},{"issue":"20","key":"pone.0331996.ref015","doi-asserted-by":"crossref","first-page":"2543","DOI":"10.1161\/01.CIR.0000100560.46946.EA","article-title":"Case definitions for acute coronary heart disease in epidemiology and clinical research studies: a statement from the AHA Council on Epidemiology and Prevention; AHA Statistics Committee; World Heart Federation Council on Epidemiology and Prevention; the European Society of Cardiology Working Group on Epidemiology and Prevention; Centers for Disease Control and Prevention; and the National Heart, Lung, and Blood Institute","volume":"108","author":"RV Luepker","year":"2003","journal-title":"Circulation"},{"issue":"1","key":"pone.0331996.ref016","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1038\/ki.2014.328","article-title":"The definition of acute kidney injury and its use in practice","volume":"87","author":"ME Thomas","year":"2015","journal-title":"Kidney Int"},{"issue":"19","key":"pone.0331996.ref017","doi-asserted-by":"crossref","first-page":"1737","DOI":"10.1056\/NEJMoa2102953","article-title":"New creatinine- and cystatin C-based equations to estimate GFR without race","volume":"385","author":"LA Inker","year":"2021","journal-title":"The New England J Med"},{"issue":"3","key":"pone.0331996.ref018","article-title":"Biomarkers of kidney tubule health, CKD progression, and acute kidney injury in SPRINT (Systolic Blood Pressure Intervention Trial) participants","volume":"78","author":"AL Bullen","year":"2021","journal-title":"Am J Kidney Dis The Official J National Kidney Found"},{"issue":"2","key":"pone.0331996.ref019","doi-asserted-by":"crossref","first-page":"470","DOI":"10.1016\/j.kint.2019.03.024","article-title":"The SPRINT trial suggests that markers of tubule cell function in the urine associate with risk of subsequent acute kidney injury while injury markers elevate after the injury","volume":"96","author":"AL Bullen","year":"2019","journal-title":"Kidney Int"},{"issue":"3","key":"pone.0331996.ref020","doi-asserted-by":"crossref","first-page":"349","DOI":"10.2215\/CJN.02780319","article-title":"Urine markers of kidney tubule cell injury and kidney function decline in SPRINT trial participants with CKD","volume":"15","author":"R Malhotra","year":"2020","journal-title":"Clin J Am Soc Nephrol"},{"issue":"1","key":"pone.0331996.ref021","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1053\/j.ajkd.2018.07.015","article-title":"Effects of intensive blood pressure lowering on kidney tubule injury in CKD: a longitudinal subgroup analysis in SPRINT","volume":"73","author":"R Malhotra","year":"2019","journal-title":"American J Kidney Dis: The Official J National Kidney Found"},{"issue":"10","key":"pone.0331996.ref022","doi-asserted-by":"crossref","first-page":"956","DOI":"10.1001\/jama.2022.1751","article-title":"Predictive accuracy of a perioperative laboratory test-based prediction model for moderate to severe acute kidney injury after cardiac surgery","volume":"327","author":"S Demirjian","year":"2022","journal-title":"JAMA"},{"issue":"1","key":"pone.0331996.ref023","doi-asserted-by":"crossref","first-page":"338","DOI":"10.1186\/s13019-022-02066-4","article-title":"Pre-operative kidney biomarkers and risks for death, cardiovascular and chronic kidney disease events after cardiac surgery: the TRIBE-AKI study","volume":"17","author":"G Vasquez-Rios","year":"2022","journal-title":"J Cardiothorac Surg"},{"issue":"6","key":"pone.0331996.ref024","doi-asserted-by":"crossref","first-page":"904","DOI":"10.1053\/j.ajkd.2012.05.014","article-title":"Associations of urinary levels of kidney injury molecule 1 (KIM-1) and neutrophil gelatinase-associated lipocalin (NGAL) with kidney function decline in the Multi-Ethnic Study of Atherosclerosis (MESA)","volume":"60","author":"CA Peralta","year":"2012","journal-title":"Am J Kidney Dis"},{"issue":"1","key":"pone.0331996.ref025","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1186\/s13054-016-1352-z","article-title":"Acute kidney injury following cardiac surgery: current understanding and future directions","volume":"20","author":"JB O\u2019Neal","year":"2016","journal-title":"Crit Care"},{"issue":"2","key":"pone.0331996.ref026","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1213\/ANE.0000000000005458","article-title":"Prevention of cardiac surgery-associated acute kidney injury by implementing the KDIGO guidelines in high-risk patients identified by biomarkers: the PrevAKI-multicenter randomized controlled trial","volume":"133","author":"A Zarbock","year":"2021","journal-title":"Anesth Analg"},{"issue":"11","key":"pone.0331996.ref027","doi-asserted-by":"crossref","first-page":"1551","DOI":"10.1007\/s00134-016-4670-3","article-title":"Prevention of cardiac surgery-associated AKI by implementing the KDIGO guidelines in high risk patients identified by biomarkers: the PrevAKI randomized controlled trial","volume":"43","author":"M Meersch","year":"2017","journal-title":"Intensive Care Med"},{"issue":"12","key":"pone.0331996.ref028","doi-asserted-by":"crossref","first-page":"1712","DOI":"10.1023\/A:1018903014204","article-title":"Aqueous stability of human epidermal growth factor 1-48","volume":"11","author":"RI Senderoff","year":"1994","journal-title":"Pharmaceutical Research"},{"issue":"12","key":"pone.0331996.ref029","doi-asserted-by":"crossref","first-page":"806","DOI":"10.1038\/s41581-024-00881-7","article-title":"Advances in uromodulin biology and potential clinical applications","volume":"20","author":"A Nanamatsu","year":"2024","journal-title":"Nat Rev Nephrol"},{"issue":"7","key":"pone.0331996.ref030","doi-asserted-by":"crossref","first-page":"1136","DOI":"10.1093\/clinchem\/48.7.1136","article-title":"Alpha1-microglobulin is stable in human urine ex vivo","volume":"48","author":"MM Payn","year":"2002","journal-title":"Clin Chem"},{"issue":"1","key":"pone.0331996.ref031","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1053\/j.ajkd.2015.04.040","article-title":"Long-term stability of urinary biomarkers of acute kidney injury in children","volume":"67","author":"MP Schuh","year":"2016","journal-title":"Am J Kidney Dis"},{"issue":"10","key":"pone.0331996.ref032","doi-asserted-by":"crossref","DOI":"10.1515\/cclm-2019-0152","article-title":"Stability of tubular damage markers epidermal growth factor and heparin-binding EGF-like growth factor in urine","volume":"57","author":"LR Harskamp","year":"2019","journal-title":"Clin Chem Lab Med"}],"container-title":["PLOS One"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0331996","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T17:55:10Z","timestamp":1780336510000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0331996"}},"subtitle":[],"editor":[{"given":"Ramada Rateb","family":"Khasawneh","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2026,6,1]]},"references-count":32,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2026,6,1]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0331996","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,1]]}}}