{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T17:59:23Z","timestamp":1771523963073,"version":"3.50.1"},"reference-count":19,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2020,10,21]],"date-time":"2020-10-21T00:00:00Z","timestamp":1603238400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000274","name":"British Heart Foundation","doi-asserted-by":"publisher","award":["CS\/16\/1\/31878"],"award-info":[{"award-number":["CS\/16\/1\/31878"]}],"id":[{"id":"10.13039\/501100000274","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,2,18]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>BACKGROUND<\/jats:title>\n                  <jats:p>Genome-wide association studies have identified single nucleotide polymorphisms (SNPs) near the uromodulin gene (UMOD) affecting uromodulin excretion and blood pressure (BP). Uromodulin is almost exclusively expressed in the thick ascending limb (TAL) of the loop of Henle and its effect on BP appears to be mediated via the TAL sodium transporter, NKCC2. Loop-diuretics block NKCC2 but are not commonly used in hypertension management. Volume overload is one of the primary drivers for uncontrolled hypertension, so targeting loop-diuretics to individuals who are more likely to respond to this drug class, using the UMOD genotype, could be an efficient precision medicine strategy.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>METHODS<\/jats:title>\n                  <jats:p>The BHF UMOD Trial is a genotype-blinded, multicenter trial comparing BP response to torasemide between individuals possessing the AA genotype of the SNP rs13333226 and those possessing the G allele. 240 participants (\u226518 years) with uncontrolled BP, on \u22651 antihypertensive agent for \u22653 months, will receive treatment with Torasemide, 5 mg daily for 16 weeks. Uncontrolled BP is average home systolic BP (SBP) &amp;gt;135 mmHg and\/or diastolic BP &amp;gt;85 mmHg. The primary outcome is the change in 24-hour ambulatory SBP area under the curve between baseline and end of treatment. Sample size was calculated to detect a 4 mmHg difference between groups at 90% power. Approval by West of Scotland Research Ethics Committee 5 (16\/WS\/0160).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>RESULTS<\/jats:title>\n                  <jats:p>The study should conclude August 2021.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>CONCLUSIONS<\/jats:title>\n                  <jats:p>If our hypothesis is confirmed, a genotype-based treatment strategy for loop diuretics would help reduce the burden of uncontrolled hypertension.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>CLINICAL TRIALS REGISTRATION<\/jats:title>\n                  <jats:p>https:\/\/clinicaltrials.gov\/ct2\/show\/NCT03354897.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/ajh\/hpaa166","type":"journal-article","created":{"date-parts":[[2020,10,8]],"date-time":"2020-10-08T19:16:02Z","timestamp":1602184562000},"page":"92-99","source":"Crossref","is-referenced-by-count":15,"title":["Rationale and Design of the Genotype-Blinded Trial of Torasemide for the Treatment of Hypertension (BHF UMOD)"],"prefix":"10.1093","volume":"34","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6596-647X","authenticated-orcid":false,"given":"Linsay","family":"McCallum","sequence":"first","affiliation":[{"name":"Institute of Cardiovascular and Medical Sciences, BHF Glasgow Cardiovascular Research Centre, University of Glasgow, Glasgow, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katriona","family":"Brooksbank","sequence":"additional","affiliation":[{"name":"Institute of Cardiovascular and Medical Sciences, BHF Glasgow Cardiovascular Research Centre, University of Glasgow, Glasgow, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7262-7000","authenticated-orcid":false,"given":"Alex","family":"McConnachie","sequence":"additional","affiliation":[{"name":"Robertson Centre for Biostatistics, Institute of Health and Wellbeing, University of Glasgow, Glasgow, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alisha","family":"Aman","sequence":"additional","affiliation":[{"name":"Institute of Cardiovascular and Medical Sciences, BHF Glasgow Cardiovascular Research Centre, University of Glasgow, Glasgow, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stefanie","family":"Lip","sequence":"additional","affiliation":[{"name":"Institute of Cardiovascular and Medical Sciences, BHF Glasgow Cardiovascular Research Centre, University of Glasgow, Glasgow, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jesse","family":"Dawson","sequence":"additional","affiliation":[{"name":"Institute of Cardiovascular and Medical Sciences, BHF Glasgow Cardiovascular Research Centre, University of Glasgow, Glasgow, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Iain M","family":"MacIntyre","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology Unit and Research Centre, University of Edinburgh\/BHF Centre of Research Excellence, Edinburgh, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas M","family":"MacDonald","sequence":"additional","affiliation":[{"name":"MEMO Research, University of Dundee, Ninewells Hospital and Medical School, Dundee, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David J","family":"Webb","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology Unit and Research Centre, University of Edinburgh\/BHF Centre of Research Excellence, Edinburgh, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3869-5808","authenticated-orcid":false,"given":"Sandosh","family":"Padmanabhan","sequence":"additional","affiliation":[{"name":"Institute of Cardiovascular and Medical Sciences, BHF Glasgow Cardiovascular Research Centre, University of Glasgow, Glasgow, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2020,10,21]]},"reference":[{"key":"2021021815190053200_CIT0001","doi-asserted-by":"crossref","first-page":"914","DOI":"10.1056\/NEJM199304013281303","article-title":"Single-drug therapy for hypertension in men. 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