{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T08:12:35Z","timestamp":1791360755786,"version":"4.3.1"},"reference-count":62,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"3","funder":[{"DOI":"10.13039\/100017540","name":"NHLBI Division of Intramural Research","doi-asserted-by":"crossref","award":["National Institutes of Health (NIH) R01DK130997, R01DK130870, R01HL128973, R01HL139629, R01HL148354"],"award-info":[{"award-number":["National Institutes of Health (NIH) R01DK130997, R01DK130870, R01HL128973, R01HL139629, R01HL148354"]}],"id":[{"id":"10.13039\/100017540","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["JASN"],"published-print":{"date-parts":[[2026,3]]},"abstract":"<jats:sec>\n                    <jats:title>Key Points<\/jats:title>\n                    <jats:p>\n                      <jats:list list-type=\"bullet\">\n                        <jats:list-item>\n                          <jats:p>Adjuvant thiazide improved diuretic response more than loop dose increase in patients with acute heart failure and diuretic resistance.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>The underlying diuretic resistance mechanism did not identify preferential response to either diuretic escalation strategy.<\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>The optimal therapy for loop diuretic resistance may differ if caused by resistance at the site of action in the loop of Henle (diuretic resistance at the loop of Henle [DR-Loop]) versus compensatory distal reabsorption (diuretic resistance due to distal sodium reabsorption [DR-Distal]). This study primarily aimed to compare diuretic strategies and explore whether targeting the underlying diuretic resistance mechanism could optimize diuretic response.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Patients hospitalized with heart failure and diuretic resistance (6-hour cumulative natriuresis &lt;100 mmol after intravenous [IV] loop diuretic) were randomized 1:1 to (\n                      <jats:italic toggle=\"yes\">1<\/jats:italic>\n                      ) 2.5\u00d7 IV loop dose intensification or (\n                      <jats:italic toggle=\"yes\">2<\/jats:italic>\n                      ) IV chlorothiazide addition to the same loop diuretic. The primary trial outcome was the increase in 6-hour natriuresis between strategies. Exploratory analyses of diuretic resistance mechanism were performed. Diuretic resistance mechanisms were categorized using the fractional excretion of lithium (FE\n                      <jats:sub>Li<\/jats:sub>\n                      ), a metric evaluating sodium exit from the loop of Henle. DR-Loop was defined as a loop diuretic\u2013induced increase in FE\n                      <jats:sub>Li<\/jats:sub>\n                      below the median and DR-Distal as an increase in FE\n                      <jats:sub>Li<\/jats:sub>\n                      above the median at the screening visit.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Patients (mean age 68\u00b112 years, 40% women) were randomized to loop dose intensification (\n                      <jats:italic toggle=\"yes\">n<\/jats:italic>\n                      =51) or adjuvant thiazide (\n                      <jats:italic toggle=\"yes\">n<\/jats:italic>\n                      =52). The primary outcome of increase in 6-hour natriuresis improved significantly with both strategies. However, chlorothiazide addition produced a significantly larger improvement in 6-hour natriuresis (107 mmol increase [95% confidence interval (CI), 81 to 132]) compared with loop augmentation (49 mmol increase [95% CI, 31 to 66]; treatment effect 58 mmol [95% CI, 27 to 89];\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      &lt; 0.001). Paradoxically, loop intensification augmented natriuresis less in patients with DR-Loop compared with DR-Distal (27\u00b139 versus 75\u00b177 mmol, respectively,\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      = 0.004), and adjuvant thiazide did not increase natriuresis more in patients with DR-Distal versus DR-Loop (92\u00b171 versus 105\u00b186 mmol, respectively,\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      = 0.54).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Strategies of loop dose intensification and adjuvant thiazide both improved diuretic response, with a significantly larger augmentation of natriuresis with adjuvant thiazide. The underlying diuretic resistance mechanism did not identify a preferential response to either therapy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Clinical Trial registry name and registration number:<\/jats:title>\n                    <jats:p>ClinicalTrials.gov, Diagnosing and Targeting Mechanisms of Diuretic Resistance in Heart Failure NCT02546583.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1681\/asn.0000000887","type":"journal-article","created":{"date-parts":[[2025,9,12]],"date-time":"2025-09-12T16:00:30Z","timestamp":1757692830000},"page":"533-544","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":6,"title":["Loop Diuretic Dose Intensification versus Adjuvant Thiazide for Diuretic Resistance in Acute Heart Failure"],"prefix":"10.1681","volume":"37","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1623-3445","authenticated-orcid":false,"given":"Veena S.","family":"Rao","sequence":"first","affiliation":[{"name":"Section of Cardiovascular Medicine, Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4919-0146","authenticated-orcid":false,"given":"Zachary L.","family":"Cox","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Practice, Lipscomb University College of Pharmacy, Nashville, Tennessee"},{"name":"Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8800-7298","authenticated-orcid":false,"given":"Juan B.","family":"Ivey-Miranda","sequence":"additional","affiliation":[{"name":"Section of Cardiovascular Medicine, Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut"},{"name":"Hospital de Cardiologia, Instituto Mexicano del Seguro Social, Mexico City, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julieta","family":"Moreno-Villagomez","sequence":"additional","affiliation":[{"name":"Section of Cardiovascular Medicine, Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut"},{"name":"Facultad de Estudios Superiores Iztacala, Universidad Nacional Autonoma de Mexico, Mexico City, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7422-3480","authenticated-orcid":false,"given":"Daniela","family":"Ramos-Mastache","sequence":"additional","affiliation":[{"name":"Facultad de Estudios Superiores Iztacala, Universidad Nacional Autonoma de Mexico, Mexico City, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2510-4266","authenticated-orcid":false,"given":"Christopher","family":"Maulion","sequence":"additional","affiliation":[{"name":"Section of Cardiovascular Medicine, Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lavanya","family":"Bellumkonda","sequence":"additional","affiliation":[{"name":"Section of Cardiovascular Medicine, Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5733-949X","authenticated-orcid":false,"given":"Jeffrey","family":"Turner","sequence":"additional","affiliation":[{"name":"Section of Nephrology, Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut"}],"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":"Section of Cardiovascular Medicine, Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut"},{"name":"Clinical and Translational Research Accelerator, Yale University School of Medicine, New Haven, Connecticut"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9559-204X","authenticated-orcid":false,"given":"Michael G.","family":"Shilpak","sequence":"additional","affiliation":[{"name":"Kidney Health Research Collaborative, Department of Medicine, University of California San Francisco, San Francisco, California"}],"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":"Kidney Health Research Collaborative, Department of Medicine, University of California San Francisco, San Francisco, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0719-8705","authenticated-orcid":false,"given":"Paul","family":"Welling","sequence":"additional","affiliation":[{"name":"Departments of Medicine and Physiology, John Hopkins School of Medicine, Baltimore, Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0943-1037","authenticated-orcid":false,"given":"Christopher S.","family":"Wilcox","sequence":"additional","affiliation":[{"name":"Division of Nephrology and Hypertension Center, Georgetown University, Washington, DC"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2915-265X","authenticated-orcid":false,"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":"Biff","family":"Forbush","sequence":"additional","affiliation":[{"name":"Department of Cellular and Molecular Physiology, Yale University School of Medicine, New Haven, Connecticut"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey M.","family":"Testani","sequence":"additional","affiliation":[{"name":"Section of Cardiovascular Medicine, Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2025,9,12]]},"reference":[{"issue":"2","key":"B1-20260428","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."},{"issue":"19","key":"B2-20260428","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."},{"issue":"11","key":"B3-20260428","doi-asserted-by":"crossref","first-page":"943","DOI":"10.1016\/j.jchf.2020.05.013","article-title":"In-Hospital therapy for heart failure with reduced ejection fraction in the United States","volume":"8","author":"Greene","year":"2020","journal-title":"JACC Heart Fail."},{"issue":"1","key":"B4-20260428","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1007\/s10741-019-09851-9","article-title":"Loop diuretic resistance complicating acute heart failure","volume":"25","author":"Cox","year":"2020","journal-title":"Heart Fail Rev."},{"issue":"10","key":"B5-20260428","doi-asserted-by":"crossref","first-page":"1178","DOI":"10.1016\/j.jacc.2019.12.059","article-title":"Diuretic therapy for patients with heart failure: JACC state-of-the-art review","volume":"75","author":"Felker","year":"2020","journal-title":"J Am Coll Cardiol."},{"issue":"1","key":"B6-20260428","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1067\/mhj.2002.123144","article-title":"Diuretic resistance predicts mortality in patients with advanced heart failure","volume":"144","author":"Neuberg","year":"2002","journal-title":"Am Heart J."},{"issue":"5","key":"B7-20260428","doi-asserted-by":"crossref","first-page":"622","DOI":"10.1111\/j.0306-5251.2003.02054.x","article-title":"Furosemide responsiveness, non-adherence and resistance during the chronic treatment of heart failure: a longitudinal study","volume":"57","author":"MacFadyen","year":"2004","journal-title":"Br J Clin Pharmacol."},{"key":"B8-20260428","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1016\/j.ijcard.2016.09.005","article-title":"Different diuretic dose and response in acute decompensated heart failure: clinical characteristics and prognostic significance","volume":"224","author":"Palazzuoli","year":"2016","journal-title":"Int J Cardiol."},{"issue":"2","key":"B9-20260428","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."},{"issue":"7","key":"B10-20260428","doi-asserted-by":"crossref","first-page":"428","DOI":"10.1016\/j.cardfail.2018.02.002","article-title":"Determinants of diuretic responsiveness and associated outcomes during acute heart failure hospitalization: an analysis from the NHLBI heart failure network clinical trials","volume":"24","author":"Kiernan","year":"2018","journal-title":"J Card Fail."},{"issue":"5","key":"B11-20260428","doi-asserted-by":"crossref","first-page":"729","DOI":"10.1002\/ejhf.2053","article-title":"Renal profiling based on estimated glomerular filtration rate and spot urine sodium identifies high-risk acute heart failure patients","volume":"23","author":"Biegus","year":"2021","journal-title":"Eur J Heart Fail."},{"issue":"10","key":"B12-20260428","doi-asserted-by":"crossref","first-page":"1978","DOI":"10.1002\/ejhf.2662","article-title":"Assessing intrinsic renal sodium avidity in acute heart failure: implications in predicting and guiding decongestion","volume":"24","author":"Martens","year":"2022","journal-title":"Eur J Heart Fail."},{"issue":"11","key":"B13-20260428","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."},{"issue":"8","key":"B14-20260428","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."},{"issue":"2","key":"B15-20260428","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1002\/ejhf.1369","article-title":"The use of diuretics in heart failure with congestion - a position statement from the Heart Failure Association of the European Society of Cardiology","volume":"21","author":"Mullens","year":"2019","journal-title":"Eur J Heart Fail."},{"issue":"5","key":"B16-20260428","first-page":"e1","article-title":"2022 AHA\/ACC\/HFSA guideline for the management of heart failure: a report of the American College of Cardiology\/American Heart Association Joint Committee on clinical practice guidelines","volume":"28","year":"2022","journal-title":"J Am Coll Cardiol."},{"issue":"36","key":"B17-20260428","doi-asserted-by":"crossref","first-page":"3599","DOI":"10.1093\/eurheartj\/ehab368","article-title":"2021 ESC guidelines for the diagnosis and treatment of acute and chronic heart failure","volume":"42","author":"McDonagh","year":"2021","journal-title":"Eur Heart J."},{"issue":"13","key":"B18-20260428","doi-asserted-by":"crossref","first-page":"1241","DOI":"10.1016\/j.jacc.2024.06.002","article-title":"2024 ACC expert consensus decision pathway on clinical assessment, management, and trajectory of patients hospitalized with heart failure focused update: a report of the American College of Cardiology Solution Set Oversight Committee","volume":"84","author":"Hollenberg","year":"2024","journal-title":"J Am Coll Cardiol."},{"issue":"5","key":"B19-20260428","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1093\/eurheartj\/ehac689","article-title":"Combining loop with thiazide diuretics for decompensated heart failure: the CLOROTIC trial","volume":"44","author":"Trull\u00e0s","year":"2023","journal-title":"Eur Heart J."},{"issue":"19","key":"B20-20260428","doi-asserted-by":"crossref","first-page":"1527","DOI":"10.1016\/j.jacc.2010.06.034","article-title":"Combination of loop diuretics with thiazide-type diuretics in heart failure","volume":"56","author":"Jentzer","year":"2010","journal-title":"J Am Coll Cardiol."},{"issue":"6","key":"B21-20260428","doi-asserted-by":"crossref","first-page":"4458","DOI":"10.1002\/ehf2.12949","article-title":"Mechanisms of diuretic resistance study: design and rationale","volume":"7","author":"Cox","year":"2020","journal-title":"ESC Heart Fail."},{"issue":"2","key":"B22-20260428","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1681\/ASN.0000000000000269","article-title":"Empagliflozin in heart failure: regional nephron sodium handling effects","volume":"35","author":"Rao","year":"2024","journal-title":"J Am Soc Nephrol."},{"issue":"4","key":"B23-20260428","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1159\/000183252","article-title":"Lithium clearance: a new method for determining proximal and distal tubular reabsorption of sodium and water","volume":"37","author":"Thomsen","year":"1984","journal-title":"Nephron."},{"issue":"2","key":"B24-20260428","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1159\/000190264","article-title":"The validity of lithium clearance as an index of sodium and water delivery from the proximal tubules","volume":"77","author":"Thomsen","year":"1997","journal-title":"Nephron."},{"issue":"2","key":"B25-20260428","doi-asserted-by":"crossref","first-page":"753","DOI":"10.1016\/S0022-3565(25)22159-0","article-title":"Lithium clearance as an indicator of proximal tubular sodium handling during furosemide diuresis","volume":"246","author":"Christensen","year":"1988","journal-title":"J Pharmacol Exp Ther."},{"issue":"1","key":"B26-20260428","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1038\/ki.1989.153","article-title":"Evaluation of lithium clearance as a marker of proximal tubule sodium handling","volume":"36","author":"Koomans","year":"1989","journal-title":"Kidney Int."},{"issue":"6","key":"B27-20260428","doi-asserted-by":"crossref","first-page":"695","DOI":"10.1016\/j.jacc.2020.12.022","article-title":"Natriuretic equation to predict loop diuretic response in patients with heart failure","volume":"77","author":"Rao","year":"2021","journal-title":"J Am Coll Cardiol."},{"issue":"1","key":"B28-20260428","doi-asserted-by":"crossref","first-page":"e002370","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."},{"issue":"1","key":"B29-20260428","doi-asserted-by":"crossref","first-page":"668","DOI":"10.1002\/ehf2.14801","article-title":"External validation of the natriuretic response prediction equation to discriminate diuretic response in heart failure","volume":"12","author":"Ram\u00edrez-S\u00e1nchez","year":"2025","journal-title":"ESC Heart Fail."},{"issue":"5","key":"B30-20260428","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1042\/cs0760539","article-title":"Acute effects of thiazides, with and without carbonic anhydrase inhibiting activity, on lithium and free water clearance in man","volume":"76","author":"Boer","year":"1989","journal-title":"Clin Sci (Lond)."},{"issue":"6","key":"B31-20260428","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1056\/NEJM199808063390607","article-title":"Diuretic therapy","volume":"339","author":"Brater","year":"1998","journal-title":"New Engl J Med."},{"issue":"10","key":"B32-20260428","doi-asserted-by":"crossref","first-page":"2049","DOI":"10.1161\/HYPERTENSIONAHA.124.23122","article-title":"UMOD genotype-blinded trial of ambulatory blood pressure response to torasemide","volume":"81","author":"McCallum","year":"2024","journal-title":"Hypertension."},{"issue":"12","key":"B33-20260428","doi-asserted-by":"crossref","first-page":"1655","DOI":"10.1038\/nm.3384","article-title":"Common noncoding UMOD gene variants induce salt-sensitive hypertension and kidney damage by increasing uromodulin expression","volume":"19","author":"Trudu","year":"2013","journal-title":"Nat Med."},{"issue":"6","key":"B34-20260428","doi-asserted-by":"crossref","first-page":"F1062","DOI":"10.1152\/ajprenal.00233.2017","article-title":"Tamm-Horsfall protein\/uromodulin deficiency elicits tubular compensatory responses leading to hypertension and hyperuricemia","volume":"314","author":"Liu","year":"2018","journal-title":"Am J Physiol Renal Physiol."},{"issue":"4","key":"B35-20260428","doi-asserted-by":"crossref","first-page":"F859","DOI":"10.1152\/ajprenal.00106.2008","article-title":"Isoforms of renal Na-K-2Cl cotransporter NKCC2: expression and functional significance","volume":"295","author":"Castrop","year":"2008","journal-title":"Am J Physiol Renal Physiol."},{"issue":"5","key":"B36-20260428","doi-asserted-by":"crossref","first-page":"1540","DOI":"10.1038\/s44318-025-00368-6","article-title":"Structural basis for human NKCC1 inhibition by loop diuretic drugs","volume":"44","author":"Zhao","year":"2025","journal-title":"EMBO J."},{"issue":"9","key":"B37-20260428","doi-asserted-by":"crossref","first-page":"F991","DOI":"10.1152\/ajprenal.00432.2014","article-title":"Physiology and pathophysiology of the renal Na-K-2Cl cotransporter (NKCC2)","volume":"307","author":"Castrop","year":"2014","journal-title":"Am J Physiol Renal Physiol."},{"issue":"29","key":"B38-20260428","doi-asserted-by":"crossref","first-page":"26946","DOI":"10.1074\/jbc.M303435200","article-title":"Short-term stimulation of the renal Na-K-Cl cotransporter (NKCC2) by vasopressin involves phosphorylation and membrane translocation of the protein","volume":"278","author":"Gim\u00e9nez","year":"2003","journal-title":"J Biol Chem."},{"issue":"20","key":"B39-20260428","doi-asserted-by":"crossref","first-page":"1964","DOI":"10.1056\/NEJMra1703100","article-title":"Diuretic treatment in heart failure","volume":"377","author":"Ellison","year":"2017","journal-title":"New Engl J Med."},{"issue":"7","key":"B40-20260428","doi-asserted-by":"crossref","first-page":"1335","DOI":"10.1681\/ASN.V1271335","article-title":"Loop diuretic infusion increases thiazide-sensitive Na(+)\/Cl(-)-cotransporter abundance: role of aldosterone","volume":"12","author":"Abdallah","year":"2001","journal-title":"J Am Soc Nephrol."},{"issue":"12","key":"B41-20260428","doi-asserted-by":"crossref","first-page":"2147","DOI":"10.2215\/CJN.05920613","article-title":"Distal convoluted tubule","volume":"9","author":"Subramanya","year":"2014","journal-title":"Clin J Am Soc Nephrol."},{"issue":"1","key":"B42-20260428","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1172\/JCI113847","article-title":"Adaptation of the distal convoluted tubule of the rat. Structural and functional effects of dietary salt intake and chronic diuretic infusion","volume":"83","author":"Ellison","year":"1989","journal-title":"J Clin Invest."},{"issue":"4","key":"B43-20260428","doi-asserted-by":"crossref","first-page":"F457","DOI":"10.1152\/ajprenal.00339.2013","article-title":"Acute inhibition of NCC does not activate distal electrogenic Na+ reabsorption or kaliuresis","volume":"306","author":"Hunter","year":"2014","journal-title":"Am J Physiol Renal Physiol."},{"issue":"2","key":"B44-20260428","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1007\/s11906-006-0013-z","article-title":"Sodium transporters in the distal nephron and disease implications","volume":"8","author":"Ecelbarger","year":"2006","journal-title":"Curr Hypertens Rep."},{"issue":"3 Pt 2","key":"B45-20260428","first-page":"F546","article-title":"Thiazide-sensitive sodium chloride cotransport in early distal tubule","volume":"253","author":"Ellison","year":"1987","journal-title":"Am J Physiol."},{"issue":"5","key":"B46-20260428","doi-asserted-by":"crossref","first-page":"1627","DOI":"10.1172\/JCI40145","article-title":"The Na+-dependent chloride-bicarbonate exchanger SLC4A8 mediates an electroneutral Na+ reabsorption process in the renal cortical collecting ducts of mice","volume":"120","author":"Leviel","year":"2010","journal-title":"J Clin Invest."},{"issue":"8","key":"B47-20260428","doi-asserted-by":"crossref","first-page":"1257","DOI":"10.1093\/ndt\/gfu307","article-title":"The multiple roles of pendrin in the kidney","volume":"30","author":"Soleimani","year":"2015","journal-title":"Nephrol Dial Transplant."},{"issue":"11","key":"B48-20260428","doi-asserted-by":"crossref","first-page":"e79327","DOI":"10.1371\/journal.pone.0079327","article-title":"Potentiation of the effect of thiazide derivatives by carbonic anhydrase inhibitors: molecular mechanisms and potential clinical implications","volume":"8","author":"Zahedi","year":"2013","journal-title":"PLoS One."},{"issue":"33","key":"B49-20260428","doi-asserted-by":"crossref","first-page":"13368","DOI":"10.1073\/pnas.1202671109","article-title":"Double knockout of pendrin and Na-Cl cotransporter (NCC) causes severe salt wasting, volume depletion, and renal failure","volume":"109","author":"Soleimani","year":"2012","journal-title":"Proc Natl Acad Sci U S A."},{"issue":"3","key":"B50-20260428","doi-asserted-by":"crossref","first-page":"e0150918","DOI":"10.1371\/journal.pone.0150918","article-title":"The role of epithelial sodium channel ENaC and the apical Cl-\/HCO3- exchanger pendrin in compensatory salt reabsorption in the setting of Na-Cl cotransporter (NCC) inactivation","volume":"11","author":"Patel-Chamberlin","year":"2016","journal-title":"PLoS One."},{"issue":"4","key":"B51-20260428","doi-asserted-by":"crossref","first-page":"F427","DOI":"10.1152\/ajprenal.00022.2013","article-title":"Cortical distal nephron Cl(-) transport in volume homeostasis and blood pressure regulation","volume":"305","author":"Wall","year":"2013","journal-title":"Am J Physiol Renal Physiol."},{"issue":"4","key":"B52-20260428","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1038\/ng1297-411","article-title":"Pendred syndrome is caused by mutations in a putative sulphate transporter gene (PDS)","volume":"17","author":"Everett","year":"1997","journal-title":"Nat Genet."},{"issue":"11","key":"B53-20260428","doi-asserted-by":"crossref","first-page":"1928","DOI":"10.1681\/ASN.2009121257","article-title":"Pendrin modulates ENaC function by changing luminal HCO3","volume":"21","author":"Pech","year":"2010","journal-title":"J Am Soc Nephrol."},{"issue":"12","key":"B54-20260428","doi-asserted-by":"crossref","first-page":"3499","DOI":"10.1681\/ASN.2016070720","article-title":"Pendrin-A new target for diuretic therapy?","volume":"27","author":"Wagner","year":"2016","journal-title":"J Am Soc Nephrol."},{"issue":"1","key":"B55-20260428","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1681\/ASN.2015070734","article-title":"Double knockout of the Na+-driven Cl-\/HCO3- exchanger and Na+\/Cl- cotransporter induces hypokalemia and volume depletion","volume":"28","author":"Sinning","year":"2017","journal-title":"J Am Soc Nephrol."},{"issue":"12","key":"B56-20260428","doi-asserted-by":"crossref","first-page":"3706","DOI":"10.1681\/ASN.2015121312","article-title":"Small-molecule inhibitors of pendrin potentiate the diuretic action of furosemide","volume":"27","author":"Cil","year":"2016","journal-title":"J Am Soc Nephrol."},{"issue":"3","key":"B57-20260428","doi-asserted-by":"crossref","first-page":"420","DOI":"10.1002\/cpt.754","article-title":"Emerging targets of diuretic therapy","volume":"102","author":"Cheng","year":"2017","journal-title":"Clin Pharmacol Ther."},{"issue":"2","key":"B58-20260428","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1016\/j.beem.2017.04.011","article-title":"Pendred syndrome","volume":"31","author":"W\u00e9meau","year":"2017","journal-title":"Best Pract Res Clin Endocrinol Metab."},{"issue":"6","key":"B59-20260428","doi-asserted-by":"crossref","first-page":"302","DOI":"10.1097\/00000441-200112000-00002","article-title":"Liddle syndrome: genetics and mechanisms of Na+ channel defects","volume":"322","author":"Warnock","year":"2001","journal-title":"Am J Med Sci."},{"issue":"1","key":"B60-20260428","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1007\/s11255-017-1653-4","article-title":"Gitelman syndrome: an analysis of the underlying pathophysiologic mechanisms of acid-base and electrolyte abnormalities","volume":"50","author":"Filippatos","year":"2018","journal-title":"Int Urol Nephrol."},{"issue":"3","key":"B62-20260428","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1159\/000335114","article-title":"Impact of bicarbonate, ammonium chloride, and acetazolamide on hepatic and renal SLC26A4 expression","volume":"28","author":"Alesutan","year":"2011","journal-title":"Cell Physiol Biochem."},{"issue":"22","key":"B63-20260428","doi-asserted-by":"crossref","first-page":"2153","DOI":"10.1056\/NEJMra0907219","article-title":"Use of diuretics in patients with hypertension","volume":"361","author":"Ernst","year":"2009","journal-title":"New Engl J Med."}],"container-title":["Journal of the American Society of Nephrology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ovid.com\/10.1681\/ASN.0000000887","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T19:42:14Z","timestamp":1786131734000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ovid.com\/10.1681\/ASN.0000000887"}},"subtitle":["Mechanistic Randomized Controlled Trial"],"short-title":[],"issued":{"date-parts":[[2025,9,12]]},"references-count":62,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2026]]}},"URL":"https:\/\/doi.org\/10.1681\/asn.0000000887","relation":{},"ISSN":["1046-6673","1533-3450"],"issn-type":[{"value":"1046-6673","type":"print"},{"value":"1533-3450","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,9,12]]},"assertion":[{"value":"2025-08-02","name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-09-08","name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}}]}}