{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,6]],"date-time":"2026-09-06T10:39:14Z","timestamp":1788691154298,"version":"build-2803163510"},"reference-count":28,"publisher":"Oxford University Press (OUP)","issue":"8","license":[{"start":{"date-parts":[[2017,1,19]],"date-time":"2017-01-19T00:00:00Z","timestamp":1484784000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"name":"CTSA award","award":["NIH UL1TR000128"],"award-info":[{"award-number":["NIH UL1TR000128"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2017,8,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Loop diuretic resistance is a common barrier to effective decongestion in acute heart failure (AHF), and is associated with poor outcome. Specific mechanisms underlying diuretic resistance are currently unknown in contemporary AHF patients. We therefore aimed to determine the relative importance of defects in diuretic delivery vs. renal tubular response in determining diuretic response (DR) in AHF.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and results<\/jats:title>\n                    <jats:p>Fifty AHF patients treated with intravenous bumetanide underwent a 6-h timed urine collection for sodium and bumetanide clearance. Whole-kidney DR was defined as sodium excreted per doubling of administered loop diuretic and represents the sum of defects in drug delivery and renal tubular response. Tubular DR, defined as sodium excreted per doubling of renally cleared (urinary) loop diuretic, captures resistance specifically in the renal tubule. Median administered bumetanide dose was 3.0 (2.0\u20134.0) mg with 52 (33\u201377)% of the drug excreted into the urine. Significant between-patient variability was present as the administered dose only explained 39% of variability in the quantity of bumetanide in urine. Cumulatively, factors related to drug delivery such as renal bumetanide clearance, administered dose, and urea clearance explained 28% of the variance in whole-kidney DR. However, resistance at the level of the renal tubule (tubular DR) explained 71% of the variability in whole-kidney DR.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Defects at the level of the renal tubule are substantially more important than reduced diuretic delivery in determining diuretic resistance in patients with AHF.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ejhf.757","type":"journal-article","created":{"date-parts":[[2017,1,20]],"date-time":"2017-01-20T02:09:35Z","timestamp":1484878175000},"page":"1014-1022","source":"Crossref","is-referenced-by-count":104,"title":["Renal Tubular Resistance is the Primary Driver for Loop Diuretic Resistance in Acute Heart Failure"],"prefix":"10.1093","volume":"19","author":[{"given":"Jozine M.","family":"ter Maaten","sequence":"first","affiliation":[{"name":"Program of Applied Translational Research, Yale University , New Haven, CT ,","place":["USA"]},{"name":"Department of Cardiology, University Medical Centre Groningen, University of Groningen , Groningen ,","place":["the Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Veena S.","family":"Rao","sequence":"additional","affiliation":[{"name":"Program of Applied Translational Research, Yale University , New Haven, CT ,","place":["USA"]},{"name":"Department of Pharmacy Services, Yale\u2013New Haven Hospital , New Haven, CT ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer S.","family":"Hanberg","sequence":"additional","affiliation":[{"name":"Program of Applied Translational Research, Yale University , New Haven, CT ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F.","family":"Perry Wilson","sequence":"additional","affiliation":[{"name":"Program of Applied Translational Research, Yale University , New Haven, CT ,","place":["USA"]},{"name":"Department of Internal Medicine, Yale University , New Haven, CT ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lavanya","family":"Bellumkonda","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Yale University , New Haven, CT ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mahlet","family":"Assefa","sequence":"additional","affiliation":[{"name":"Program of Applied Translational Research, Yale University , New Haven, CT ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.","family":"Sam Broughton","sequence":"additional","affiliation":[{"name":"Program of Applied Translational Research, Yale University , New Haven, CT ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie","family":"D'Ambrosi","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Services, Yale\u2013New Haven Hospital , New Haven, CT ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"W.H.","family":"Wilson Tang","sequence":"additional","affiliation":[{"name":"Section of Heart Failure and Cardiac Transplantation, Cleveland Clinic , Cleveland, OH ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin","family":"Damman","sequence":"additional","affiliation":[{"name":"Department of Cardiology, University Medical Centre Groningen, University of Groningen , Groningen ,","place":["the Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adriaan A.","family":"Voors","sequence":"additional","affiliation":[{"name":"Department of Cardiology, University Medical Centre Groningen, University of Groningen , Groningen ,","place":["the Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David H.","family":"Ellison","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Nephrology and Hypertension, Oregon Health and Science University , Portland, OR ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey M.","family":"Testani","sequence":"additional","affiliation":[{"name":"Program of Applied Translational Research, Yale University , New Haven, CT ,","place":["USA"]},{"name":"Department of Internal Medicine, Yale University , New Haven, CT ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2017,1,19]]},"reference":[{"key":"2026011721192360500_ejhf757-bib-0001","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1016\/j.cardfail.2010.08.010","article-title":"Hospitalization epidemic in patients with heart failure: risk factors, risk prediction, knowledge gaps, and future directions","volume":"17","author":"Giamouzis","year":"2011","journal-title":"J Card Fail"},{"key":"2026011721192360500_ejhf757-bib-0002","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1007\/s10741-005-6127-6","article-title":"Overview of acutely decompensated congestive heart failure (ADHF): a report from the ADHERE registry","volume":"9","author":"Fonarow","year":"2004","journal-title":"Heart Fail Rev"},{"key":"2026011721192360500_ejhf757-bib-0003","doi-asserted-by":"crossref","first-page":"566","DOI":"10.1161\/CIRCOUTCOMES.109.853556","article-title":"Cost-consequences of ultrafiltration for acute heart failure: a decision model analysis","volume":"2","author":"Bradley","year":"2009","journal-title":"Circ Cardiovasc Qual Outcomes"},{"key":"2026011721192360500_ejhf757-bib-0004","doi-asserted-by":"crossref","first-page":"e147","DOI":"10.1016\/j.jacc.2013.05.019","article-title":"2013 ACCF\/AHA guideline for the management of heart failure: a report of the American College of Cardiology Foundation\/American Heart Association Task Force on Practice Guidelines","volume":"62","author":"Yancy","year":"2013","journal-title":"J Am Coll Cardiol"},{"key":"2026011721192360500_ejhf757-bib-0005","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1093\/eurjhf\/hfq045","article-title":"Assessing and grading congestion in acute heart failure: a scientific statement from the acute heart failure committee of the heart failure association of the European Society of Cardiology and endorsed by the European Society of Intensive Care Medicine","volume":"12","author":"Gheorghiade","year":"2010","journal-title":"Eur J Heart Fail"},{"key":"2026011721192360500_ejhf757-bib-0006","doi-asserted-by":"crossref","first-page":"S3","DOI":"10.1016\/j.amjmed.2006.09.011","article-title":"Congestion in acute heart failure syndromes: an essential target of evaluation and treatment","volume":"119","author":"Gheorghiade","year":"2006","journal-title":"Am J Med"},{"key":"2026011721192360500_ejhf757-bib-0007","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1016\/j.jacc.2008.10.041","article-title":"Acute heart failure syndromes","volume":"53","author":"Gheorghiade","year":"2009","journal-title":"J Am Coll Cardiol"},{"key":"2026011721192360500_ejhf757-bib-0008","doi-asserted-by":"crossref","first-page":"891","DOI":"10.1002\/ejhf.592","article-title":"2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: The Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC). Developed with the special contribution of the Heart Failure Association (HFA) of the ESC","volume":"18","author":"Ponikowski","year":"2016","journal-title":"Eur J Heart Fail"},{"key":"2026011721192360500_ejhf757-bib-0009","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1038\/nrcardio.2014.215","article-title":"Diuretic response in acute heart failure-pathophysiology, evaluation, and therapy","volume":"12","author":"Ter Maaten","year":"2015","journal-title":"Nat Rev Cardiol"},{"key":"2026011721192360500_ejhf757-bib-0010","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1161\/CIRCHEARTFAILURE.113.000895","article-title":"Loop diuretic efficiency: a metric of diuretic responsiveness with prognostic importance in acute decompensated heart failure","volume":"7","author":"Testani","year":"2014","journal-title":"Circ Heart Fail"},{"key":"2026011721192360500_ejhf757-bib-0011","doi-asserted-by":"crossref","first-page":"1284","DOI":"10.1093\/eurheartj\/ehu065","article-title":"Diuretic response in acute heart failure: clinical characteristics and prognostic significance","volume":"35","author":"Valente","year":"2014","journal-title":"Eur Heart J"},{"key":"2026011721192360500_ejhf757-bib-0012","doi-asserted-by":"crossref","first-page":"1230","DOI":"10.1002\/ejhf.170","article-title":"Diuretic response in patients with acute decompensated heart failure: characteristics and clinical outcome\u2014an analysis from RELAX-AHF","volume":"16","author":"Voors","year":"2014","journal-title":"Eur J Heart Fail"},{"key":"2026011721192360500_ejhf757-bib-0013","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1016\/j.ahj.2015.05.003","article-title":"Diuretic response in acute heart failure - an analysis from ASCEND-HF","volume":"170","author":"ter Maaten","year":"2015","journal-title":"Am Heart J"},{"key":"2026011721192360500_ejhf757-bib-0014","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1038\/clpt.1983.154","article-title":"Bumetanide and furosemide","volume":"34","author":"Brater","year":"1983","journal-title":"Clin Pharmacol Ther"},{"key":"2026011721192360500_ejhf757-bib-0015","doi-asserted-by":"crossref","first-page":"784","DOI":"10.1038\/clpt.1980.111","article-title":"Renal tubular secretion and effects of furosemide","volume":"27","author":"Odlind","year":"1980","journal-title":"Clin Pharmacol Ther"},{"key":"2026011721192360500_ejhf757-bib-0016","doi-asserted-by":"crossref","first-page":"682","DOI":"10.1038\/ki.1989.246","article-title":"Mechanism of impaired natriuretic response to furosemide during prolonged therapy","volume":"36","author":"Loon","year":"1989","journal-title":"Kidney Int"},{"key":"2026011721192360500_ejhf757-bib-0017","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1038\/clpt.1988.186","article-title":"Kinetics, dynamics, and bioavailability of bumetanide in healthy subjects and patients with congestive heart failure","volume":"44","author":"Cook","year":"1988","journal-title":"Clin Pharmacol Ther"},{"key":"2026011721192360500_ejhf757-bib-0018","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1038\/ki.1984.153","article-title":"Bumetanide and furosemide in heart failure","volume":"26","author":"Brater","year":"1984","journal-title":"Kidney Int"},{"key":"2026011721192360500_ejhf757-bib-0019","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1038\/ki.1982.149","article-title":"Absorption and disposition of furosemide in congestive heart failure","volume":"22","author":"Brater","year":"1982","journal-title":"Kidney Int"},{"key":"2026011721192360500_ejhf757-bib-0020","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1056\/NEJM199808063390607","article-title":"Diuretic therapy","volume":"339","author":"Brater","year":"1998","journal-title":"N Engl J Med"},{"key":"2026011721192360500_ejhf757-bib-0021","volume-title":"Brenner & Rector's the Kidney","author":"Brenner","year":"2008"},{"key":"2026011721192360500_ejhf757-bib-0022","doi-asserted-by":"crossref","first-page":"797","DOI":"10.1056\/NEJMoa1005419","article-title":"Diuretic strategies in patients with acute decompensated heart failure","volume":"364","author":"Felker","year":"2011","journal-title":"N Engl J Med"},{"key":"2026011721192360500_ejhf757-bib-0023","first-page":"450","article-title":"Response of the kidney to furosemide. I. Effects of salt intake and renal compensation","volume":"102","author":"Wilcox","year":"1983","journal-title":"J Lab Clin Med"},{"key":"2026011721192360500_ejhf757-bib-0024","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1038\/ki.1983.149","article-title":"Response of the kidney to furosemide. II. Effect of captopril on sodium balance","volume":"24","author":"Kelly","year":"1983","journal-title":"Kidney Int"},{"key":"2026011721192360500_ejhf757-bib-0025","doi-asserted-by":"crossref","first-page":"980","DOI":"10.1002\/jms.1436","article-title":"A high-throughput multicomponent screening method for diuretics, masking agents, central nervous system (CNS) stimulants and opiates in human urine by UPLC-MS\/MS","volume":"43","author":"Thorngren","year":"2008","journal-title":"J Mass Spectrom"},{"key":"2026011721192360500_ejhf757-bib-0026","doi-asserted-by":"crossref","first-page":"604","DOI":"10.7326\/0003-4819-150-9-200905050-00006","article-title":"A new equation to estimate glomerular filtration rate","volume":"150","author":"Levey","year":"2009","journal-title":"Ann Intern Med"},{"key":"2026011721192360500_ejhf757-bib-0027","doi-asserted-by":"crossref","DOI":"10.1161\/CIRCHEARTFAILURE.115.002370","article-title":"Rapid and highly accurate prediction of poor loop diuretic natriuretic response in patients with heart failure","volume":"9","author":"Testani","year":"2016","journal-title":"Circ Heart Fail"},{"key":"2026011721192360500_ejhf757-bib-0028","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1002\/cpt1975182165","article-title":"Effect of dosage regimen on natriuretic response to furosemide","volume":"18","author":"Wilson","year":"1975","journal-title":"Clin Pharmacol Ther"}],"container-title":["European Journal of Heart Failure"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fejhf.757","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/academic.oup.com\/eurjhf\/article-pdf\/19\/8\/1014\/66328502\/eurjhf_19_8_1014.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/eurjhf\/article-pdf\/19\/8\/1014\/66328502\/eurjhf_19_8_1014.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,18]],"date-time":"2026-01-18T02:21:15Z","timestamp":1768702875000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/eurjhf\/article\/19\/8\/1014\/8418568"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,1,19]]},"references-count":28,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2017,1,19]]},"published-print":{"date-parts":[[2017,8,1]]}},"URL":"https:\/\/doi.org\/10.1002\/ejhf.757","relation":{},"ISSN":["1388-9842","1879-0844"],"issn-type":[{"value":"1388-9842","type":"print"},{"value":"1879-0844","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2017,8]]},"published":{"date-parts":[[2017,1,19]]}}}