{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T02:47:42Z","timestamp":1786589262164,"version":"build-2736575974"},"reference-count":32,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"5","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["CJASN"],"published-print":{"date-parts":[[2019,5]]},"abstract":"\n Background and objectives<\/jats:title>\n Diuretic resistance can limit successful decongestion of patients with heart failure. Because loop diuretics tightly bind albumin, low serum albumin and high urine albumin can theoretically limit diuretic delivery to the site of action. However, it is unknown if this represents a clinically relevant mechanism of diuretic resistance in human heart failure.<\/jats:p>\n <\/jats:sec>\n \n Design, setting, participants, & measurements<\/jats:title>\n \n In total, 208 outpatients with heart failure at the Yale Transitional Care Center undergoing diuretic treatment were studied. Blood and urine chemistries were collected at baseline and 1.5 hours postdiuretic administration. Urine diuretic levels were normalized to urine creatinine and adjusted for diuretic dose administered, and diuretic efficiency was calculated as sodium output per doubling of the loop diuretic dose. Findings were validated in an inpatient heart failure cohort (\n n<\/jats:italic>\n =60).\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Serum albumin levels in the outpatient cohort ranged from 2.4 to 4.9 g\/dl, with a median of 3.7 g\/dl (interquartile range, 3.5\u20134.1). Serum albumin had no association with urinary diuretic delivery (\n r<\/jats:italic>\n =\u22120.05;\n P<\/jats:italic>\n =0.52), but higher levels weakly correlated with better diuretic efficiency (\n r<\/jats:italic>\n =0.17;\n P<\/jats:italic>\n =0.02). However, serum albumin inversely correlated with systemic inflammation as assessed by plasma IL-6 (\n r<\/jats:italic>\n =\u22120.35;\n P<\/jats:italic>\n <0.001), and controlling for IL-6 eliminated the diuretic efficiency-serum albumin association (\n r<\/jats:italic>\n =0.12;\n P<\/jats:italic>\n =0.12). In the inpatient cohort, there was no association between serum albumin and urinary diuretic excretion (\n r<\/jats:italic>\n =0.15;\n P<\/jats:italic>\n =0.32) or diuretic efficiency (\n r<\/jats:italic>\n =\u22120.16;\n P<\/jats:italic>\n =0.25). In the outpatient cohort, 39% of patients had microalbuminuria, and 18% had macroalbuminuria. There was no correlation between albuminuria and diuretic efficiency after adjusting for kidney function (\n r<\/jats:italic>\n =\u22120.02;\n P<\/jats:italic>\n =0.89). Results were similar in the inpatient cohort.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n Serum albumin levels were not associated with urinary diuretic excretion, and urinary albumin levels were not associated with diuretic efficiency.<\/jats:p>\n <\/jats:sec>","DOI":"10.2215\/cjn.11600918","type":"journal-article","created":{"date-parts":[[2019,4,22]],"date-time":"2019-04-22T12:55:14Z","timestamp":1555937714000},"page":"712-718","source":"Crossref","is-referenced-by-count":32,"title":["Serum and Urine Albumin and Response to Loop Diuretics in Heart Failure"],"prefix":"10.2215","volume":"14","author":[{"given":"Antonios","family":"Charokopos","sequence":"first","affiliation":[{"name":"Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew","family":"Griffin","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Section of Cardiovascular Medicine,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Veena S.","family":"Rao","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Section of Cardiovascular Medicine,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lesley","family":"Inker","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Tufts Medical Center, Boston, Massachusetts; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Krishna","family":"Sury","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Section of Nephrology, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"Asher","sequence":"additional","affiliation":[{"name":"Department of Comparative Medicine, Yale University School of Medicine, New Haven, Connecticut;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey","family":"Turner","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Section of Nephrology, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Devin","family":"Mahoney","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Section of Cardiovascular Medicine,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zachary L.","family":"Cox","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Practice, Lipscomb University College of Pharmacy, Nashville, Tennessee"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2633-2412","authenticated-orcid":false,"given":"F. Perry","family":"Wilson","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Section of Nephrology, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey M.","family":"Testani","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Section of Cardiovascular Medicine,"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2019,4,22]]},"reference":[{"key":"B1-20230813","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":"B2-20230813","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":"B3-20230813","doi-asserted-by":"crossref","first-page":"392","DOI":"10.1016\/j.cardfail.2014.03.006","article-title":"Insufficient natriuretic response to continuous intravenous furosemide is associated with poor long-term outcomes in acute decompensated heart failure.","volume":"20","author":"Singh","year":"2014","journal-title":"J Card Fail"},{"key":"B4-20230813","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1080\/AC.70.3.3080630","article-title":"Determinants and impact of the natriuretic response to diuretic therapy in heart failure with reduced ejection fraction and volume overload.","volume":"70","author":"Verbrugge","year":"2015","journal-title":"Acta Cardiol"},{"key":"B5-20230813","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1016\/j.cardfail.2014.05.007","article-title":"Loop diuretic resistance in heart failure: Resistance etiology-based strategies to restoring diuretic efficacy.","volume":"20","author":"Cox","year":"2014","journal-title":"J Card Fail"},{"key":"B6-20230813","doi-asserted-by":"crossref","first-page":"798","DOI":"10.1681\/ASN.V133798","article-title":"New insights into diuretic use in patients with chronic renal disease.","volume":"13","author":"Wilcox","year":"2002","journal-title":"J Am Soc Nephrol"},{"key":"B7-20230813","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1038\/ki.1987.192","article-title":"Mechanism of furosemide resistance in analbuminemic rats and hypoalbuminemic patients.","volume":"32","author":"Inoue","year":"1987","journal-title":"Kidney Int"},{"key":"B8-20230813","first-page":"F475","article-title":"Facilitation by serum albumin of renal tubular secretion of organic anions.","volume":"256","author":"Besseghir","year":"1989","journal-title":"Am J Physiol"},{"key":"B9-20230813","doi-asserted-by":"crossref","first-page":"885","DOI":"10.1111\/j.1476-5381.1996.tb15755.x","article-title":"The influence of moderate hypoalbuminaemia on the renal metabolism and dynamics of furosemide in the rabbit.","volume":"119","author":"Pichette","year":"1996","journal-title":"Br J Pharmacol"},{"key":"B10-20230813","first-page":"81","article-title":"Role of plasma protein binding on renal metabolism and dynamics of furosemide in the rabbit.","volume":"27","author":"Pichette","year":"1999","journal-title":"Drug Metab Dispos"},{"key":"B11-20230813","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1016\/0024-3205(80)90238-6","article-title":"Resistance of proteinuric rats to furosemide: Urinary drug protein binding as a determinant of drug effect.","volume":"26","author":"Green","year":"1980","journal-title":"Life Sci"},{"key":"B12-20230813","first-page":"1097","article-title":"Intratubular albumin blunts the response to furosemide-A mechanism for diuretic resistance in the nephrotic syndrome.","volume":"252","author":"Kirchner","year":"1990","journal-title":"J Pharmacol Exp Ther"},{"key":"B13-20230813","doi-asserted-by":"crossref","first-page":"418","DOI":"10.1038\/ki.1991.228","article-title":"Binding inhibitors restore furosemide potency in tubule fluid containing albumin.","volume":"40","author":"Kirchner","year":"1991","journal-title":"Kidney Int"},{"key":"B14-20230813","first-page":"122","article-title":"Furosemide disposition in normal and proteinuric rats: Urinary drug-protein binding as a determinant of drug excretion.","volume":"218","author":"Green","year":"1981","journal-title":"J Pharmacol Exp Ther"},{"key":"B15-20230813","doi-asserted-by":"crossref","first-page":"334","DOI":"10.1177\/1074248412474347","article-title":"The effect of continuous infusion loop diuretics in patients with acute decompensated heart failure with hypoalbuminemia.","volume":"18","author":"Bleske","year":"2013","journal-title":"J Cardiovasc Pharmacol Ther"},{"key":"B16-20230813","doi-asserted-by":"crossref","first-page":"884","DOI":"10.1016\/j.cardfail.2016.01.015","article-title":"Clinical implications of serum albumin levels in acute heart failure: Insights from DOSE-AHF and ROSE-AHF.","volume":"22","author":"Grodin","year":"2016","journal-title":"J Card Fail"},{"key":"B17-20230813","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1007\/s00392-015-0896-2","article-title":"A combined clinical and biomarker approach to predict diuretic response in acute heart failure.","volume":"105","author":"ter Maaten","year":"2016","journal-title":"Clin Res Cardiol"},{"key":"B18-20230813","doi-asserted-by":"crossref","first-page":"3414","DOI":"10.1681\/ASN.2016111178","article-title":"Compensatory distal reabsorption drives diuretic resistance in human heart failure.","volume":"28","author":"Rao","year":"2017","journal-title":"J Am Soc Nephrol"},{"key":"B19-20230813","doi-asserted-by":"crossref","first-page":"1014","DOI":"10.1002\/ejhf.757","article-title":"Renal tubular resistance is the primary driver for loop diuretic resistance in acute heart failure.","volume":"19","author":"Ter Maaten","year":"2017","journal-title":"Eur J Heart Fail"},{"key":"B20-20230813","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"},{"issue":"Suppl 2","key":"B21-20230813","first-page":"6","article-title":"Detecting microalbuminuria by urinary albumin\/creatinine concentration ratio.","volume":"12","author":"Jensen","year":"1997","journal-title":"Nephrol Dial Transplant"},{"key":"B22-20230813","doi-asserted-by":"crossref","first-page":"1004","DOI":"10.1016\/S0272-6386(99)70442-7","article-title":"Proteinuria, albuminuria, risk, assessment, detection, elimination (PARADE): A position paper of the national kidney foundation.","volume":"33","author":"Keane","year":"1999","journal-title":"Am J Kidney Dis"},{"key":"B23-20230813","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":"B24-20230813","doi-asserted-by":"crossref","DOI":"10.1161\/CIRCHEARTFAILURE.116.003180","article-title":"Hypochloremia and diuretic resistance in heart failure: Mechanistic insights.","volume":"9","author":"Hanberg","year":"2016","journal-title":"Circ Heart Fail"},{"key":"B25-20230813","doi-asserted-by":"crossref","first-page":"601","DOI":"10.1016\/0009-9236(95)90222-8","article-title":"Bioavailability, pharmacokinetics, and pharmacodynamics of torsemide and furosemide in patients with congestive heart failure.","volume":"57","author":"Vargo","year":"1995","journal-title":"Clin Pharmacol Ther"},{"key":"B26-20230813","doi-asserted-by":"crossref","first-page":"426","DOI":"10.2165\/00003495-198428050-00003","article-title":"Bumetanide. A review of its pharmacodynamic and pharmacokinetic properties and therapeutic use.","volume":"28","author":"Ward","year":"1984","journal-title":"Drugs"},{"key":"B27-20230813","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1161\/CIRCHEARTFAILURE.112.000152","article-title":"Early evolution and correlates of urine albumin excretion in patients presenting with acutely decompensated heart failure.","volume":"6","author":"Koyama","year":"2013","journal-title":"Circ Heart Fail"},{"key":"B28-20230813","doi-asserted-by":"crossref","first-page":"543","DOI":"10.1016\/S0140-6736(09)61378-7","article-title":"Albuminuria in chronic heart failure: Prevalence and prognostic importance.","volume":"374","author":"Jackson","year":"2009","journal-title":"Lancet"},{"key":"B29-20230813","doi-asserted-by":"crossref","first-page":"933","DOI":"10.1002\/ejhf.963","article-title":"Inflammation and cardio-renal interactions in heart failure: A potential role for interleukin-6.","volume":"20","author":"Hanberg","year":"2018","journal-title":"Eur J Heart Fail"},{"key":"B30-20230813","doi-asserted-by":"crossref","first-page":"1100","DOI":"10.1681\/ASN.V1161100","article-title":"Urinary protein binding does not affect response to furosemide in patients with nephrotic syndrome.","volume":"11","author":"Agarwal","year":"2000","journal-title":"J Am Soc Nephrol"},{"key":"B31-20230813","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1159\/000457099","article-title":"Albumin binding of bumetanide.","volume":"9","author":"Robertson","year":"1986","journal-title":"Dev Pharmacol Ther"},{"key":"B32-20230813","doi-asserted-by":"crossref","first-page":"24556","DOI":"10.1074\/jbc.272.39.24556","article-title":"Ion and bumetanide binding by the Na-K-Cl cotransporter. Importance of transmembrane domains.","volume":"272","author":"Isenring","year":"1997","journal-title":"J Biol Chem"}],"container-title":["Clinical Journal of the American Society of Nephrology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ovid.com\/01277230-201905000-00012","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T13:42:21Z","timestamp":1786369341000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ovid.com\/01277230-201905000-00012"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,4,22]]},"references-count":32,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2019]]}},"URL":"https:\/\/doi.org\/10.2215\/cjn.11600918","relation":{},"ISSN":["1555-9041","1555-905X"],"issn-type":[{"value":"1555-9041","type":"print"},{"value":"1555-905X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,4,22]]}}}