{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T11:48:18Z","timestamp":1786362498437,"version":"build-2736575974"},"reference-count":40,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"24","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2025,12,16]]},"abstract":"\n Background<\/jats:title>\n \n Loop diuretics require functioning kidney tubules to increase the excretion of sodium into urine thereby relieving congestion in patients with acute heart failure (\n AHF<\/jats:styled-content>\n ). Whether biomarkers of kidney tubular health are associated with the natriuretic response of loop diuretics in\n AHF<\/jats:styled-content>\n is unknown.\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n Spot urine sodium and 14 urine biomarkers of tubular health were measured after intravenous loop diuretic administration on the day of enrollment in 418 patients with\n AHF<\/jats:styled-content>\n from\n AKINESIS<\/jats:styled-content>\n (Acute Kidney Injury Neutrophil Gelatinase\u2013Associated Lipocalin [NGAL] Evaluation of Symptomatic Heart Failure Study). The association of each biomarker with urine sodium concentration was assessed with multivariable linear regression.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n The mean age was 71\u00b112\u2009years, 64% were men, average estimated glomerular filtration rate was 56\u00b124\u2009\n mL<\/jats:styled-content>\n \/min per 1.73\u2009m\n 2<\/jats:sup>\n , and urine sodium was 94\u00b148\u2009\n mEq<\/jats:styled-content>\n \/L. Higher urine concentrations of \u03b1\u20101\u2010microglobulin (\u22125.0\u2009\n mEq<\/jats:styled-content>\n \/L [95%\n CI,<\/jats:styled-content>\n \u22128.3 to \u22121.6\u2009\n mEq<\/jats:styled-content>\n \/L]), insulin\u2010like growth factor\u2013binding protein\u20107 (\n IGFBP<\/jats:styled-content>\n \u20107\u2009\n mEq<\/jats:styled-content>\n \/L; \u22124.1 [95%\n CI,<\/jats:styled-content>\n \u22128.1 to 0.0\u2009\n mEq<\/jats:styled-content>\n \/L]), tissue inhibitor of metalloproteinases 2 (\n TIMP<\/jats:styled-content>\n \u20102; \u22123.6\u2009\n mEq<\/jats:styled-content>\n \/L [95%\n CI,<\/jats:styled-content>\n \u22126.5 to \u22120.7\u2009\n mEq<\/jats:styled-content>\n \/L]),\n IGFBP<\/jats:styled-content>\n \u20107*\n TIMP<\/jats:styled-content>\n \u20102 product (\u22125.1\u2009\n mEq<\/jats:styled-content>\n \/L [95%\n CI,<\/jats:styled-content>\n \u22126.6 to \u22123.7\u2009\n mEq<\/jats:styled-content>\n \/L]), interleukin 18 (\u22128.2\u2009\n mEq<\/jats:styled-content>\n \/L [95%\n CI,<\/jats:styled-content>\n \u221213.2 to \u22123.1\u2009\n mEq<\/jats:styled-content>\n \/L]), kidney injury molecule 1 (\u22122.4\u2009\n mEq<\/jats:styled-content>\n \/L [95%\n CI,<\/jats:styled-content>\n \u22124.4 to \u22120.3\u2009\n mEq<\/jats:styled-content>\n \/L]), and chemokine ligand 14 (\u22122.3\u2009\n mEq<\/jats:styled-content>\n \/L [95%\n CI,<\/jats:styled-content>\n \u22124.0 to \u22120.5\u2009\n mEq<\/jats:styled-content>\n \/L]) were associated with lower urine sodium concentration after adjustment for confounders including estimated glomerular filtration rate and urine albumin.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n \n Urine biomarkers of tubular health are associated with lower natriuretic response to loop diuretics in patients with\n AHF<\/jats:styled-content>\n . Kidney tubule health may be an underappreciated contributor to diuretic responsiveness in\n AHF<\/jats:styled-content>\n .\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1161\/jaha.125.044812","type":"journal-article","created":{"date-parts":[[2025,12,11]],"date-time":"2025-12-11T11:06:25Z","timestamp":1765451185000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":1,"title":["Urine Tubular Biomarkers Are Associated With Natriuresis in Patients With Acute Heart Failure"],"prefix":"10.1161","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6122-1152","authenticated-orcid":false,"given":"Nicholas","family":"Wettersten","sequence":"first","affiliation":[{"name":"San Diego Veterans Affairs Medical Center","place":["San Diego, USA"]},{"name":"University of California, San Diego","place":["La Jolla, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1270-1181","authenticated-orcid":false,"given":"Stephen","family":"Duff","sequence":"additional","affiliation":[{"name":"University College Dublin","place":["Dublin, Ireland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9053-1099","authenticated-orcid":false,"given":"Yu","family":"Horiuchi","sequence":"additional","affiliation":[{"name":"Mitsui Memorial Hospital","place":["Tokyo, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1611-7935","authenticated-orcid":false,"given":"Dirk J.","family":"van Veldhuisen","sequence":"additional","affiliation":[{"name":"University Medical Center Groningen, University of Groningen","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4040-7799","authenticated-orcid":false,"given":"Sagar","family":"Raturi","sequence":"additional","affiliation":[{"name":"University of Groningen","place":["The Netherlands"]}],"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":"Veterans Affairs San Francisco Healthcare System","place":["San Francisco, USA"]}],"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":"University of California","place":["San Francisco, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alan","family":"Maisel","sequence":"additional","affiliation":[{"name":"University of California, San Diego","place":["La Jolla, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8516-1839","authenticated-orcid":false,"given":"Patrick T.","family":"Murray","sequence":"additional","affiliation":[{"name":"University College Dublin","place":["Dublin, Ireland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8084-9869","authenticated-orcid":false,"given":"Joachim","family":"Ix","sequence":"additional","affiliation":[{"name":"University of California San Diego","place":["San Diego, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurjhf\/hfq045"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1002\/ejhf.890"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.carpath.2011.11.007"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1159\/000164149"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1002\/ejhf.1492"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11897-019-0424-1"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cardfail.2014.03.006"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1093\/ehjqcco\/qcac007"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehs444"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1002\/ejhf.1428"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1002\/ejhf.2053"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1002\/ejhf.757"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1681\/asn.2016111178"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1053\/j.ajkd.2021.03.026"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2016.06.055"},{"key":"e_1_3_2_17_2","first-page":"1","article-title":"Kidney Disease: Improving Global Outcomes (KDIGO) Acute Kidney Injury Work Group. 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