{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T02:42:14Z","timestamp":1793328134411,"version":"4.5.0"},"reference-count":47,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"11","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JASN"],"published-print":{"date-parts":[[2017,11]]},"abstract":"<jats:p>\n                    Understanding the tubular location of diuretic resistance (DR) in heart failure (HF) is critical to developing targeted treatment strategies. Rodents chronically administered loop diuretics develop DR due to compensatory distal tubular sodium reabsorption, but whether this translates to human DR is unknown. We studied consecutive patients with HF (\n                    <jats:italic toggle=\"yes\">n<\/jats:italic>\n                    =128) receiving treatment with loop diuretics at the Yale Transitional Care Center. We measured the fractional excretion of lithium (FELi), the gold standard for\n                    <jats:italic toggle=\"yes\">in vivo<\/jats:italic>\n                    assessment of proximal tubular and loop of Henle sodium handling, to assess sodium exit after loop diuretic administration and FENa to assess the net sodium excreted into the urine. The mean\u00b1SD prediuretic FELi was 16.2%\u00b19.5%, similar to that in a control cohort without HF not receiving diuretics (\n                    <jats:italic toggle=\"yes\">n<\/jats:italic>\n                    =52; 16.6%\u00b19.2%;\n                    <jats:italic toggle=\"yes\">P<\/jats:italic>\n                    =0.82). Administration of a median of 160 (interquartile range, 40\u2013270) mg intravenous furosemide equivalents increased FELi by 12.6%\u00b110.8% (\n                    <jats:italic toggle=\"yes\">P<\/jats:italic>\n                    &lt;0.001) but increased FENa by only 4.8%\u00b13.3%. Thus, only 34% (interquartile range, 15.6%\u201375.7%) of the estimated diuretic-induced sodium release did not undergo distal reabsorption. After controlling for urine diuretic levels, the increase in FELi explained only 6.4% of the increase in FENa (\n                    <jats:italic toggle=\"yes\">P<\/jats:italic>\n                    =0.002). These data suggest that administration of high-dose loop diuretics to patients with HF yields meaningful increases in sodium exit from the proximal tubule\/loop of Henle. However, little of this sodium seems to reach the urine, consistent with findings from animal models that indicate that distal tubular compensatory sodium reabsorption is a primary driver of DR.\n                  <\/jats:p>","DOI":"10.1681\/asn.2016111178","type":"journal-article","created":{"date-parts":[[2017,7,24]],"date-time":"2017-07-24T20:20:11Z","timestamp":1500927611000},"page":"3414-3424","source":"Crossref","is-referenced-by-count":110,"title":["Compensatory Distal Reabsorption Drives Diuretic Resistance in Human Heart Failure"],"prefix":"10.1681","volume":"28","author":[{"given":"Veena S.","family":"Rao","sequence":"first","affiliation":[{"name":"Department of Internal Medicine and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noah","family":"Planavsky","sequence":"additional","affiliation":[{"name":"Department of Geology and Geophysics, Yale University, New Haven, Connecticut;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer S.","family":"Hanberg","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tariq","family":"Ahmad","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meredith A.","family":"Brisco-Bacik","sequence":"additional","affiliation":[{"name":"Department of Medicine, Cardiovascular Division, Lewis Katz School of Medicine at Temple University, Philadelphia, Pennsylvania;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francis P.","family":"Wilson","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine and"},{"name":"Program of Applied Translational Research, Yale University School of Medicine, New Haven, Connecticut;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Jacoby","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"W.H. Wilson","family":"Tang","sequence":"additional","affiliation":[{"name":"Section of Heart Failure and Cardiac Transplantation, Cleveland Clinic, Cleveland, Ohio;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David Z.I.","family":"Cherney","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Medicine, Toronto General Hospital and Toronto General Hospital Research Institute, Toronto, Ontario, Canada;"},{"name":"Department of Physiology, University of Toronto, Toronto, Ontario, Canada; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David H.","family":"Ellison","sequence":"additional","affiliation":[{"name":"Oregon Clinical and Translational Research Institute, Oregon Health and Science University, Portland, Oregon"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey M.","family":"Testani","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine and"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2017,7,24]]},"reference":[{"issue":"Suppl 1","key":"B1-20231016","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":"B2-20231016","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":"B3-20231016","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":"B4-20231016","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1016\/j.jacc.2012.09.038","article-title":"Rehospitalization for heart failure: Problems and perspectives.","volume":"61","author":"Gheorghiade","year":"2013","journal-title":"J Am Coll Cardiol"},{"key":"B5-20231016","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1007\/s11897-006-0030-x","article-title":"Diuretic resistance in heart failure.","volume":"3","author":"Iyengar","year":"2006","journal-title":"Curr Heart Fail Rep"},{"key":"B6-20231016","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1159\/000047397","article-title":"Diuretic therapy and resistance in congestive heart failure.","volume":"96","author":"Ellison","year":"2001","journal-title":"Cardiology"},{"key":"B7-20231016","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":"B8-20231016","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":"B10-20231016","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1172\/JCI113847","article-title":"Adaptation of the distal convoluted tubule of the rat. 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