{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T22:05:29Z","timestamp":1789596329640,"version":"build-2803163510"},"reference-count":33,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"3","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2015,3,10]]},"abstract":"<jats:sec xml:lang=\"en\">\n            <jats:title>Background<\/jats:title>\n            <jats:p xml:lang=\"en\">Endothelin 1 (ET\u20101) contributes to chronic kidney disease (CKD) development and progression, and endothelin receptor antagonists are being investigated as a novel therapy for CKD. The proET\u20101 peptides, endothelin\u2010like domain peptide (ELDP) and C\u2010terminal pro\u2010ET\u20101 (CT\u2010proET\u20101), are both potential biomarkers of CKD and response to therapy with endothelin antagonists.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Methods and Results<\/jats:title>\n            <jats:p xml:lang=\"en\">\n              We assessed plasma and urine ELDP and plasma CT\u2010proET\u20101 in CKD patients with minimal comorbidity. Next, in a randomized double\u2010blind crossover study of 27 subjects with proteinuric CKD, we examined the effects of 6\u00a0weeks of treatment with placebo, sitaxentan (endothelin A antagonist), and nifedipine on these peptides alongside the primary end points of proteinuria, blood pressure, and arterial stiffness. Plasma ELDP and CT\u2010proET\u20101 increased with CKD stage (both\n              <jats:italic>P<\/jats:italic>\n              &lt;0.0001), correlating inversely with estimated glomerular filtration rate (both\n              <jats:italic>P<\/jats:italic>\n              &lt;0.0001). Following intervention, placebo and nifedipine did not affect plasma and urine ELDP or plasma CT\u2010proET\u20101. Sitaxentan increased both plasma ELDP and CT\u2010proET\u20101 (baseline versus week 6\u00b1SEM: ELDP, 11.8\u00b10.5 versus 13.4\u00b10.6\u00a0fmol\/mL; CT\u2010proET\u20101, 20.5\u00b11.2 versus 23.3\u00b11.5\u00a0fmol\/mL; both\n              <jats:italic>P<\/jats:italic>\n              &lt;0.0001). Plasma ET\u20101 was unaffected by any treatment. Following sitaxentan, plasma ELDP and CT\u2010proET\u20101 correlated negatively with 24\u2010hour urinary sodium excretion.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p xml:lang=\"en\">\n              ELDP and CT\u2010proET\u20101 increase in CKD and thus are potentially useful biomarkers of renal injury. Increases in response to endothelin A antagonism may reflect\n              <jats:italic>EDN1<\/jats:italic>\n              upregulation, which may partly explain fluid retention with these agents.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Clinical Trial Registration<\/jats:title>\n            <jats:p xml:lang=\"en\">\n              URL:\n              <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"http:\/\/www.clinicalTrials.gov\">www.clinicalTrials.gov<\/jats:ext-link>\n              Unique identifier: NCT00810732\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/jaha.114.001624","type":"journal-article","created":{"date-parts":[[2015,3,24]],"date-time":"2015-03-24T02:32:29Z","timestamp":1427164349000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":21,"title":["Plasma Pro\u2010Endothelin\u20101 Peptide Concentrations Rise in Chronic Kidney Disease and Following Selective Endothelin A Receptor Antagonism"],"prefix":"10.1161","volume":"4","author":[{"given":"Neeraj","family":"Dhaun","sequence":"first","affiliation":[{"name":"BHF Centre of Research Excellence, The Queen's Medical Research Institute, University of Edinburgh, 47 Little France Crescent, Edinburgh, UK, EH16 4TJ"},{"name":"Department of Renal Medicine, Royal Infirmary of Edinburgh, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jale","family":"Yuzugulen","sequence":"additional","affiliation":[{"name":"William Harvey Research Institute, Barts &amp; the London School of Medicine, Queen Mary University of London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert A.","family":"Kimmitt","sequence":"additional","affiliation":[{"name":"BHF Centre of Research Excellence, The Queen's Medical Research Institute, University of Edinburgh, 47 Little France Crescent, Edinburgh, UK, EH16 4TJ"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth G.","family":"Wood","sequence":"additional","affiliation":[{"name":"William Harvey Research Institute, Barts &amp; the London School of Medicine, Queen Mary University of London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pajaree","family":"Chariyavilaskul","sequence":"additional","affiliation":[{"name":"BHF Centre of Research Excellence, The Queen's Medical Research Institute, University of Edinburgh, 47 Little France Crescent, Edinburgh, UK, EH16 4TJ"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iain M.","family":"MacIntyre","sequence":"additional","affiliation":[{"name":"BHF Centre of Research Excellence, The Queen's Medical Research Institute, University of Edinburgh, 47 Little France Crescent, Edinburgh, UK, EH16 4TJ"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jane","family":"Goddard","sequence":"additional","affiliation":[{"name":"Department of Renal Medicine, Royal Infirmary of Edinburgh, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David J.","family":"Webb","sequence":"additional","affiliation":[{"name":"BHF Centre of Research Excellence, The Queen's Medical Research Institute, University of Edinburgh, 47 Little France Crescent, Edinburgh, UK, EH16 4TJ"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roger","family":"Corder","sequence":"additional","affiliation":[{"name":"William Harvey Research Institute, Barts &amp; the London School of Medicine, Queen Mary University of London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(05)17789-7"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0272-6386(98)70145-3"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.0000095676.90936.80"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1097\/01.ASN.0000129114.92265.32"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2005121256"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00060.2009"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1111\/bcp.12064"},{"key":"e_1_3_2_9_2","first-page":"F331","article-title":"Increased renal endothelin production in rats with reduced renal mass","volume":"260","author":"Benigni A","year":"1991","unstructured":"Benigni A, Perico N, Gaspari F, Zoja C, Bellizzi M, Gabanelli M, Remuzzi G. 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K\/doqi clinical practice guidelines for chronic kidney disease: evaluation, classification, and stratification. Am J Kidney Dis. 2002;39:S1\u2013S266.","journal-title":"Am J Kidney Dis"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1159\/000180580"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1159\/000102997"},{"key":"e_1_3_2_21_2","first-page":"147","article-title":"Evaluation of endothelin\u2010converting enzyme inhibitors using cultured cells","volume":"206","author":"Corder R","year":"2002","unstructured":"Corder R. Evaluation of endothelin\u2010converting enzyme inhibitors using cultured cells. 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