{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T20:22:04Z","timestamp":1791231724908,"version":"4.1.0"},"reference-count":24,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"5","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["CJASN"],"published-print":{"date-parts":[[2017,5]]},"abstract":"\n Background and objectives<\/jats:title>\n CKD is an important risk factor for cardiovascular disease (CVD) and death. We investigated whether select urine kidney injury biomarkers were associated with higher risk of heart failure (HF), CVD, and death in persons with CKD enrolled in the Chronic Renal Insufficiency Cohort (CRIC) Study.<\/jats:p>\n <\/jats:sec>\n \n Design, setting, participants, & measurements<\/jats:title>\n \n Urine kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin, liver fatty acid-binding protein, and\n N<\/jats:italic>\n -acetyl\n -\u03b2-<\/jats:italic>\n d<\/jats:sc>\n -glucosaminidase were measured in urine of a subset of CRIC participants (\n n<\/jats:italic>\n =2466). We used Cox proportional hazards regression to examine associations between these biomarkers indexed to urinary creatinine (Cr) and (\n 1<\/jats:italic>\n ) HF, (\n 2<\/jats:italic>\n ) a composite of atherosclerotic CVD events (myocardial infarction, ischemic stroke, or peripheral artery disease), and (\n 3<\/jats:italic>\n ) all-cause death.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n At baseline, mean age of study participants was 59.5\u00b110.8 years, 46% were women, and 34% had a self-reported history of any CVD. Median follow-up was 6.5 (interquartile range, 5.6\u20136.8) years. A total of 333 HF events, 282 atherosclerotic CVD events, and 440 deaths were observed during a median follow-up of 6.5 (interquartile range, 5.6\u20136.8) years. Those in the highest two quintiles of KIM-1\/Cr levels had a higher risk of HF relative to the lowest quintile (quintile 5 versus quintile 1 adjusted hazard ratio [aHR] of 1.73 [95% confidence interval, 1.05 to 2.85]).\n N<\/jats:italic>\n -acetyl\n -\u03b2-<\/jats:italic>\n d<\/jats:sc>\n -glucosaminidase\/Cr was associated with HF in continuous analyses (aHR per log SD higher 1.18 [95% confidence interval, 1.01 to 1.38]). Only KIM-1\/Cr was independently associated with atherosclerotic CVD events (aHR per log SD higher 1.21 [95% confidence interval, 1.02 to 1.41]), whereas both KIM-1\/Cr (quintile 5 versus quintile 1 aHR of 1.56 [95% confidence interval, 1.06 to 2.31]) and neutrophil gelatinase-associated lipocalin\/Cr (quintile 5 versus quintile 1 aHR of 1.82 [95% confidence interval, 1.19 to 2.8]) were associated with all-cause death.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n Selected urine kidney injury biomarkers were independently associated with higher risk of HF, CVD events, and death in CRIC. Among the biomarkers examined, only KIM-1\/Cr was associated with each outcome. Further work is needed to determine the utility of these biomarkers to improve risk prediction for these adverse outcomes.<\/jats:p>\n <\/jats:sec>","DOI":"10.2215\/cjn.08560816","type":"journal-article","created":{"date-parts":[[2017,3,2]],"date-time":"2017-03-02T20:55:14Z","timestamp":1488488114000},"page":"761-771","source":"Crossref","is-referenced-by-count":67,"title":["Urine Kidney Injury Biomarkers and Risks of Cardiovascular Disease Events and All-Cause Death: The CRIC Study"],"prefix":"10.2215","volume":"12","author":[{"given":"Meyeon","family":"Park","sequence":"first","affiliation":[{"name":"Division of Nephrology, University of California, San Francisco, San Francisco, California;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chi-yuan","family":"Hsu","sequence":"additional","affiliation":[{"name":"Division of Nephrology, University of California, San Francisco, San Francisco, California;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alan S.","family":"Go","sequence":"additional","affiliation":[{"name":"Division of Research, Kaiser Permanente Northern California, Oakland, California;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harold I.","family":"Feldman","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Biostatistics, University of Pennsylvania, Philadelphia, Pennsylvania;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dawei","family":"Xie","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Biostatistics, University of Pennsylvania, Philadelphia, Pennsylvania;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoming","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Biostatistics, University of Pennsylvania, Philadelphia, Pennsylvania;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Theodore","family":"Mifflin","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Biostatistics, University of Pennsylvania, Philadelphia, Pennsylvania;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sushrut S.","family":"Waikar","sequence":"additional","affiliation":[{"name":"Division of Renal Medicine, Brigham and Women's Hospital, Boston, Massachusetts;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Venkata S.","family":"Sabbisetti","sequence":"additional","affiliation":[{"name":"Division of Renal Medicine, Brigham and Women's Hospital, Boston, Massachusetts;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph V.","family":"Bonventre","sequence":"additional","affiliation":[{"name":"Division of Renal Medicine, Brigham and Women's Hospital, Boston, Massachusetts;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Josef","family":"Coresh","sequence":"additional","affiliation":[{"name":"Welch Center for Prevention, Epidemiology and Clinical Research, Johns Hopkins University, Baltimore, Maryland;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert G.","family":"Nelson","sequence":"additional","affiliation":[{"name":"National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, 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"}]},{"given":"John W.","family":"Kusek","sequence":"additional","affiliation":[{"name":"National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mahboob","family":"Rahman","sequence":"additional","affiliation":[{"name":"Division of Nephrology and Hypertension, Case Western Reserve University, Cleveland, Ohio; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey R.","family":"Schelling","sequence":"additional","affiliation":[{"name":"Division of Nephrology and Hypertension, Case Western Reserve University, Cleveland, Ohio; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ramachandran S.","family":"Vasan","sequence":"additional","affiliation":[{"name":"Section of Preventive Medicine and Epidemiology, Boston University, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathleen D.","family":"Liu","sequence":"additional","affiliation":[{"name":"Division of Nephrology, University of California, San Francisco, San Francisco, California;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"on behalf of the Chronic Renal Insufficiency Cohort (CRIC) Study Investigators","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"the CKD Biomarkers Consortium","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2017,3,2]]},"reference":[{"key":"B1-20230813","doi-asserted-by":"crossref","first-page":"1296","DOI":"10.1056\/NEJMoa041031","article-title":"Chronic kidney disease and the risks of death, cardiovascular events, and hospitalization.","volume":"351","author":"Go","year":"2004","journal-title":"N Engl J Med"},{"key":"B2-20230813","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1002\/path.2175","article-title":"Tubular kidney injury molecule-1 (KIM-1) in human renal disease.","volume":"212","author":"van Timmeren","year":"2007","journal-title":"J Pathol"},{"key":"B3-20230813","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":"Peralta","year":"2012","journal-title":"Am J Kidney Dis"},{"key":"B4-20230813","doi-asserted-by":"crossref","first-page":"337","DOI":"10.2215\/CJN.03530708","article-title":"Neutrophil gelatinase-associated lipocalin (NGAL) and progression of chronic kidney disease.","volume":"4","author":"Bolignano","year":"2009","journal-title":"Clin J Am Soc Nephrol"},{"key":"B5-20230813","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1053\/j.ajkd.2014.07.025","article-title":"Urine neutrophil gelatinase-associated lipocalin and risk of cardiovascular disease and death in CKD: Results from the chronic renal insufficiency cohort (CRIC) Study.","volume":"65","author":"Liu","year":"2015","journal-title":"Am J Kidney Dis"},{"key":"B6-20230813","doi-asserted-by":"crossref","first-page":"492","DOI":"10.1186\/s13054-014-0492-2","article-title":"Three-year risk of cardiovascular disease among intensive care patients with acute kidney injury: A population-based cohort study.","volume":"18","author":"Gammelager","year":"2014","journal-title":"Crit Care"},{"key":"B7-20230813","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1111\/hiv.12113","article-title":"Urinary biomarkers of kidney injury are associated with all-cause mortality in the Women\u2019s Interagency HIV Study (WIHS).","volume":"15","author":"Peralta","year":"2014","journal-title":"HIV Med"},{"key":"B8-20230813","doi-asserted-by":"crossref","first-page":"2109","DOI":"10.1681\/ASN.2015030292","article-title":"Urine injury biomarkers and risk of adverse outcomes in recipients of prevalent kidney transplants: The folic acid for vascular outcome reduction in transplantation trial.","volume":"27","author":"Bansal","year":"2016","journal-title":"J Am Soc Nephrol"},{"key":"B9-20230813","doi-asserted-by":"crossref","first-page":"F1472","DOI":"10.1152\/ajprenal.00619.2009","article-title":"Transcriptional analysis of kidneys during repair from AKI reveals possible roles for NGAL and KIM-1 as biomarkers of AKI-to-CKD transition.","volume":"298","author":"Ko","year":"2010","journal-title":"Am J Physiol Renal Physiol"},{"key":"B11-20230813","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/j.lab.2003.08.001","article-title":"Urinary fatty acid-binding protein as a new clinical marker of the progression of chronic renal disease.","volume":"143","author":"Kamijo","year":"2004","journal-title":"J Lab Clin Med"},{"issue":"Suppl 2","key":"B12-20230813","doi-asserted-by":"crossref","first-page":"S148","DOI":"10.1097\/01.ASN.0000070149.78399.CE","article-title":"The chronic renal insufficiency cohort (CRIC) study: Design and methods.","volume":"14","author":"Feldman","year":"2003","journal-title":"J Am Soc Nephrol"},{"key":"B13-20230813","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1053\/j.ajkd.2011.05.010","article-title":"CKD in Hispanics: Baseline characteristics from the CRIC (chronic renal insufficiency cohort) and Hispanic-CRIC Studies.","volume":"58","author":"Fischer","year":"2011","journal-title":"Am J Kidney Dis"},{"key":"B14-20230813","doi-asserted-by":"crossref","first-page":"1302","DOI":"10.2215\/CJN.00070109","article-title":"Chronic renal insufficiency cohort (CRIC) study: Baseline characteristics and associations with kidney function.","volume":"4","author":"Lash","year":"2009","journal-title":"Clin J Am Soc Nephrol"},{"key":"B15-20230813","article-title":"CKD Biomarkers Consortium: Urine biomarkers of tubular injury do not improve on the clinical model predicting chronic kidney disease progression","author":"Hsu","journal-title":"Kidney Int"},{"key":"B16-20230813","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1007\/s00125-014-3389-3","article-title":"Association of urinary KIM-1, L-FABP, NAG and NGAL with incident end-stage renal disease and mortality in American Indians with type 2 diabetes mellitus.","volume":"58","author":"Fufaa","year":"2015","journal-title":"Diabetologia"},{"key":"B17-20230813","doi-asserted-by":"crossref","first-page":"1956","DOI":"10.2215\/CJN.02590315","article-title":"Urinary biomarkers and risk of ESRD in the atherosclerosis risk in communities study.","volume":"10","author":"Foster","year":"2015","journal-title":"Clin J Am Soc Nephrol"},{"key":"B18-20230813","doi-asserted-by":"crossref","first-page":"894","DOI":"10.2215\/CJN.11541114","article-title":"Cross-disciplinary biomarkers research: Lessons learned by the CKD biomarkers consortium.","volume":"10","author":"Hsu","year":"2015","journal-title":"Clin J Am Soc Nephrol"},{"key":"B19-20230813","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1159\/000327618","article-title":"Metabolic syndrome, components, and cardiovascular disease prevalence in chronic kidney disease: Findings from the chronic renal insufficiency cohort (CRIC) study.","volume":"33","author":"Townsend","year":"2011","journal-title":"Am J Nephrol"},{"key":"B20-20230813","doi-asserted-by":"crossref","first-page":"250","DOI":"10.1053\/j.ajkd.2012.04.012","article-title":"Estimating GFR among participants in the chronic renal insufficiency cohort (CRIC) Study.","volume":"60","author":"Anderson","year":"2012","journal-title":"Am J Kidney Dis"},{"key":"B21-20230813","doi-asserted-by":"crossref","first-page":"408","DOI":"10.1016\/j.atherosclerosis.2013.01.009","article-title":"Urinary neutrophil gelatinase-associated lipocalin (NGAL) is associated with mortality in a community-based cohort of older Swedish men.","volume":"227","author":"Helmersson-Karlqvist","year":"2013","journal-title":"Atherosclerosis"},{"key":"B22-20230813","doi-asserted-by":"crossref","first-page":"1545","DOI":"10.1681\/ASN.2013070713","article-title":"Association of urinary injury biomarkers with mortality and cardiovascular events.","volume":"25","author":"Sarnak","year":"2014","journal-title":"J Am Soc Nephrol"},{"key":"B23-20230813","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1097\/QAI.0b013e3182737706","article-title":"Urinary markers of kidney injury and kidney function decline in HIV-infected women.","volume":"61","author":"Shlipak","year":"2012","journal-title":"J Acquir Immune Defic Syndr"},{"key":"B24-20230813","doi-asserted-by":"crossref","first-page":"358","DOI":"10.5414\/CN108668","article-title":"Associations of kidney injury markers with subclinical cardiovascular disease: The multi-ethnic study of atherosclerosis.","volume":"84","author":"Park","year":"2015","journal-title":"Clin Nephrol"},{"key":"B25-20230813","doi-asserted-by":"crossref","first-page":"2177","DOI":"10.1681\/ASN.2013070758","article-title":"Blood kidney injury molecule-1 is a biomarker of acute and chronic kidney injury and predicts progression to ESRD in type I diabetes.","volume":"25","author":"Sabbisetti","year":"2014","journal-title":"J Am Soc Nephrol"}],"container-title":["Clinical Journal of the American Society of Nephrology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ovid.com\/01277230-201705000-00009","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T13:36:36Z","timestamp":1786368996000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ovid.com\/01277230-201705000-00009"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,3,2]]},"references-count":24,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2017]]}},"URL":"https:\/\/doi.org\/10.2215\/cjn.08560816","relation":{},"ISSN":["1555-9041","1555-905X"],"issn-type":[{"value":"1555-9041","type":"print"},{"value":"1555-905X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,3,2]]}}}