{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T20:30:02Z","timestamp":1786480202515,"version":"build-2736575974"},"reference-count":25,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"12","funder":[{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["1U01DK096189"],"award-info":[{"award-number":["1U01DK096189"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["U01DK099923"],"award-info":[{"award-number":["U01DK099923"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["U01DK099914"],"award-info":[{"award-number":["U01DK099914"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["U01DK099919."],"award-info":[{"award-number":["U01DK099919."]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["R21DK100772"],"award-info":[{"award-number":["R21DK100772"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006108","name":"National Center for Advancing Translational Sciences","doi-asserted-by":"publisher","award":["UL1TR001102"],"award-info":[{"award-number":["UL1TR001102"]}],"id":[{"id":"10.13039\/100006108","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["K23DK102511"],"award-info":[{"award-number":["K23DK102511"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R03DK122240"],"award-info":[{"award-number":["R03DK122240"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Kidney360"],"published-print":{"date-parts":[[2020,12]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Combination therapy with isosorbide dinitrate (ISD) and hydralazine (HY) reduces heart failure mortality. The safety and tolerability in individuals requiring maintenance hemodialysis (HD) is unknown.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Single-center, randomized, placebo-controlled, double-blind pilot trial to explore safety and tolerability of ISD\/HY in maintenance HD. Participants were randomized to placebo or combination ISD\/HY. Dose was escalated over 3 weeks from ISD 10 mg\/HY 10 mg to ISD 40 mg\/HY 75 mg three times per day with the maximum tolerated dose maintained for the subsequent 21 weeks. Primary endpoints included adverse events, adverse events precluding further treatment with study medication, serious hypotension (\n                      <jats:italic toggle=\"yes\">i.e<\/jats:italic>\n                      ., requiring hospitalization or emergency room visit), and recurrent intra-dialytic hypotension. Efficacy signals included change in mitral annular E\u2019 velocity by tissue Doppler echocardiography and change in left ventricular coronary flow reserve on positron emission tomography.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      A total of 17 individuals were randomized to ISD\/HY (\n                      <jats:italic toggle=\"yes\">N<\/jats:italic>\n                      =7) or placebo (\n                      <jats:italic toggle=\"yes\">N<\/jats:italic>\n                      =10). All participants assigned to ISD\/HY completed dose escalation to 40\/75 mg, but dose reductions were required in two participants. No participants discontinued therapy. There were no serious hypotension events. Recurrent intradialytic hypotension was less frequent with ISD\/HY (0.47 events\/patient-year) than placebo (1.83 events\/patient-year,\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      =0.04). In contrast, nausea (ISD\/HY, 1.90 events\/patient-year; placebo, 0.50 events\/patient-year,\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      =0.03) was significantly more frequent, and headache and diarrhea were numerically but not significantly more frequent with ISD\/HY. Adverse events were more frequent with ISD\/HY (11.4 events\/patient-year) than placebo (6.31 events\/patient-year). We did not detect between-group differences in the change in E\u2019 (\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      =0.34); ISD\/HY showed a mean increase of 0.6 cm\/s (SD 1.1), and placebo showed a mean decrease of 0.04 cm\/s (SD 0.9). Changes in coronary flow reserve were minimal, \u22120.3 (0.2) with ISD\/HY and \u22120.03 (0.5) in the placebo group,\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      =0.19.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>ISD\/HY appears to be well tolerated in patients being treated with maintenance HD, but headache and gastrointestinal side effects occur more frequently with ISD\/HY compared with placebo.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.34067\/kid.0004342020","type":"journal-article","created":{"date-parts":[[2020,10,15]],"date-time":"2020-10-15T17:35:12Z","timestamp":1602783312000},"page":"1380-1389","source":"Crossref","is-referenced-by-count":6,"title":["Combination Hydralazine and Isosorbide Dinitrate in Dialysis-Dependent ESRD (HIDE): A Randomized, Placebo-Controlled, Pilot Trial"],"prefix":"10.34067","volume":"1","clinical-trial-number":[{"clinical-trial-number":"nct02228408","registry":"10.18810\/clinical-trials-gov"}],"author":[{"given":"David M.","family":"Charytan","sequence":"first","affiliation":[{"name":"Division of Nephrology, Department of Medicine, New York University Grossman School of Medicine, New York, New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jesse Y.","family":"Hsu","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, Epidemiology and Informatics, and Center for Clinical Epidemiology and Biostatistics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Finnian R.","family":"Mc Causland","sequence":"additional","affiliation":[{"name":"Renal Division, Department of Medicine, Harvard Medical School and Brigham and Women\u2019s Hospital, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sushrut S.","family":"Waikar","sequence":"additional","affiliation":[{"name":"Renal Section, Department of Medicine, Boston University Medical Center, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T. Alp","family":"Ikizler","sequence":"additional","affiliation":[{"name":"Division of Nephrology and Hypertension, Department of Medicine, and Vanderbilt Center for Kidney Disease, Vanderbilt University Medical Center, Nashville, Tennessee"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dominic S.","family":"Raj","sequence":"additional","affiliation":[{"name":"Division of Renal Diseases and Hypertension, George Washington University School of Medicine, Washington, DC"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. Richard","family":"Landis","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, Epidemiology and Informatics, and Center for Clinical Epidemiology and Biostatistics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rajnish","family":"Mehrotra","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Medicine, Kidney Research Institute, University of Washington, Seattle, Washington"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Williams","sequence":"additional","affiliation":[{"name":"Renal Division, Beth Israel Deaconess Medical Center, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcelo","family":"DiCarli","sequence":"additional","affiliation":[{"name":"Departments of Radiology and Medicine, Brigham and Women\u2019s Hospital, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hicham","family":"Skali","sequence":"additional","affiliation":[{"name":"Cardiovascular Division, Department of Medicine, Harvard Medical School and Brigham and Women\u2019s Hospital, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul L.","family":"Kimmel","sequence":"additional","affiliation":[{"name":"National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alan S.","family":"Kliger","sequence":"additional","affiliation":[{"name":"Department of Medicine, Yale School of Medicine, New Haven, Connecticut"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura M.","family":"Dember","sequence":"additional","affiliation":[{"name":"Renal, Electrolyte and Hypertension Division, and Center for Clinical Epidemiology and Biostatistics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"for the Hemodialysis Novel Therapies Consortium","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"Hemodialysis Novel Therapies Consortium","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan","family":"Himmelfarb","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amanda H","family":"Anderson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adriana M","family":"Hung","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shailendra","family":"Sharma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel E.","family":"Weiner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2020,12,31]]},"reference":[{"key":"B2-20230821","doi-asserted-by":"crossref","first-page":"F1","DOI":"10.1152\/ajprenal.00424.2007","article-title":"Nitric oxide deficiency in chronic kidney disease","volume":"294","author":"Baylis","year":"2008","journal-title":"Am J Physiol Renal Physiol"},{"key":"B3-20230821","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1111\/j.1523-1755.2005.00086.x","article-title":"Clinical and pathologic characteristics of dilated cardiomyopathy in hemodialysis patients","volume":"67","author":"Aoki","year":"2005","journal-title":"Kidney Int"},{"key":"B4-20230821","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/j.ijcard.2014.06.062","article-title":"Increased concentration of circulating angiogenesis and nitric oxide inhibitors induces endothelial to mesenchymal transition and myocardial fibrosis in patients with chronic kidney disease","volume":"176","author":"Charytan","year":"2014","journal-title":"Int J Cardiol"},{"key":"B5-20230821","doi-asserted-by":"crossref","first-page":"1018","DOI":"10.1681\/ASN.V961018","article-title":"Myocyte\/capillary mismatch in the heart of uremic patients","volume":"9","author":"Amann","year":"1998","journal-title":"J Am Soc Nephrol"},{"key":"B6-20230821","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1161\/CIRCIMAGING.108.838367","article-title":"Influence of myocardial fibrosis on left ventricular diastolic function: Noninvasive assessment by cardiac magnetic resonance and echo","volume":"2","author":"Moreo","year":"2009","journal-title":"Circ Cardiovasc Imaging"},{"issue":"4","key":"B7-20230821","doi-asserted-by":"crossref","first-page":"308","DOI":"10.1111\/j.1525-139X.2008.00454.x","article-title":"Hypertrophy and fibrosis in the cardiomyopathy of uremia--beyond coronary heart disease","volume":"21","author":"Gross","year":"2008","journal-title":"Semin Dial"},{"key":"B8-20230821","doi-asserted-by":"crossref","first-page":"950","DOI":"10.1161\/01.CIR.0000026395.19594.43","article-title":"Microvascular structural correlates of myocardial contrast echocardiography in patients with coronary artery disease and left ventricular dysfunction: Implications for the assessment of myocardial hibernation","volume":"106","author":"Shimoni","year":"2002","journal-title":"Circulation"},{"key":"B9-20230821","first-page":"H2363","article-title":"Role of capillaries in determining CBF reserve: New insights using myocardial contrast echocardiography","volume":"277","author":"Jayaweera","year":"1999","journal-title":"Am J Physiol"},{"key":"B10-20230821","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1016\/j.kint.2017.07.025","article-title":"Coronary flow reserve is predictive of the risk of cardiovascular death regardless of chronic kidney disease stage","volume":"93","author":"Charytan","year":"2018","journal-title":"Kidney Int"},{"key":"B11-20230821","doi-asserted-by":"crossref","first-page":"1465","DOI":"10.1172\/JCI118935","article-title":"Hydralazine prevents nitroglycerin tolerance by inhibiting activation of a membrane-bound NADH oxidase. A new action for an old drug","volume":"98","author":"M\u00fcnzel","year":"1996","journal-title":"J Clin Invest"},{"key":"B12-20230821","doi-asserted-by":"crossref","first-page":"1865","DOI":"10.1016\/j.bbrc.2005.10.106","article-title":"Hydralazine is a powerful inhibitor of peroxynitrite formation as a possible explanation for its beneficial effects on prognosis in patients with congestive heart failure","volume":"338","author":"Daiber","year":"2005","journal-title":"Biochem Biophys Res Commun"},{"key":"B13-20230821","doi-asserted-by":"crossref","first-page":"1547","DOI":"10.1056\/NEJM198606123142404","article-title":"Effect of vasodilator therapy on mortality in chronic congestive heart failure. Results of a Veterans Administration Cooperative Study","volume":"314","author":"Cohn","year":"1986","journal-title":"N Engl J Med"},{"key":"B14-20230821","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1016\/j.cardfail.2007.03.001","article-title":"Isosorbide dinitrate and hydralazine in a fixed-dose combination produces further regression of left ventricular remodeling in a well-treated black population with heart failure: Results from A-HeFT","volume":"13","author":"Cohn","year":"2007","journal-title":"J Card Fail"},{"key":"B15-20230821","doi-asserted-by":"crossref","first-page":"2049","DOI":"10.1056\/NEJMoa042934","article-title":"Combination of isosorbide dinitrate and hydralazine in blacks with heart failure","volume":"351","author":"Taylor","year":"2004","journal-title":"N Engl J Med"},{"key":"B16-20230821","doi-asserted-by":"crossref","first-page":"2350","DOI":"10.1253\/circj.CJ-11-0015","article-title":"E\/e\u2032 ratio is a strong prognostic predictor of mortality in patients with non-valvular atrial fibrillation with preserved left ventricular systolic function","volume":"75","author":"Park","year":"2011","journal-title":"Circ J"},{"key":"B17-20230821","doi-asserted-by":"crossref","first-page":"1025","DOI":"10.1016\/j.jcmg.2012.06.007","article-title":"Coronary vascular dysfunction and prognosis in patients with chronic kidney disease","volume":"5","author":"Murthy","year":"2012","journal-title":"JACC Cardiovasc Imaging"},{"key":"B18-20230821","doi-asserted-by":"crossref","first-page":"891","DOI":"10.1016\/S0735-1097(00)00786-5","article-title":"Relation of tissue Doppler derived myocardial velocities to myocardial structure and beta-adrenergic receptor density in humans","volume":"36","author":"Shan","year":"2000","journal-title":"J Am Coll Cardiol"},{"key":"B19-20230821","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1161\/CIRCULATIONAHA.108.847772","article-title":"Impact of myocardial fibrosis in patients with symptomatic severe aortic stenosis","volume":"120","author":"Weidemann","year":"2009","journal-title":"Circulation"},{"key":"B20-20230821","doi-asserted-by":"crossref","first-page":"694","DOI":"10.1067\/mnc.2001.119690","article-title":"The role of capillaries in determining coronary blood flow reserve: Implications for stress-induced reversible perfusion defects","volume":"8","author":"Kaul","year":"2001","journal-title":"J Nucl Cardiol"},{"key":"B21-20230821","doi-asserted-by":"crossref","first-page":"1391","DOI":"10.1016\/j.jacc.2008.05.064","article-title":"Depressed coronary flow reserve is associated with decreased myocardial capillary density in patients with heart failure due to idiopathic dilated cardiomyopathy","volume":"52","author":"Tsagalou","year":"2008","journal-title":"J Am Coll Cardiol"},{"key":"B22-20230821","doi-asserted-by":"crossref","first-page":"737","DOI":"10.1111\/j.1365-2362.1995.tb01952.x","article-title":"Human endothelial cells bioactivate organic nitrates to nitric oxide: Implications for the reinforcement of endothelial defence mechanisms","volume":"25","author":"Feelisch","year":"1995","journal-title":"Eur J Clin Invest"},{"key":"B23-20230821","doi-asserted-by":"crossref","first-page":"236","DOI":"10.5301\/JN.2011.6252","article-title":"Improvement of hypertension and LVH in maintenance hemodialysis patients treated with sustained-release isosorbide mononitrate","volume":"24","author":"Li","year":"2011","journal-title":"J Nephrol"},{"key":"B24-20230821","doi-asserted-by":"crossref","first-page":"1069","DOI":"10.3390\/ijms14011069","article-title":"Organic nitrates favor regression of left ventricular hypertrophy in hypertensive patients on chronic peritoneal dialysis","volume":"14","author":"Li","year":"2013","journal-title":"Int J Mol Sci"},{"key":"B25-20230821","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1016\/j.kint.2016.07.042","article-title":"Low-dose hydralazine prevents fibrosis in a murine model of acute kidney injury-to-chronic kidney disease progression","volume":"91","author":"Tampe","year":"2017","journal-title":"Kidney Int"},{"key":"B26-20230821","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/j.ebiom.2014.11.005","article-title":"Induction of tet3-dependent epigenetic remodeling by low-dose hydralazine attenuates progression of chronic kidney disease","volume":"2","author":"Tampe","year":"2015","journal-title":"EBioMedicine"}],"container-title":["Kidney360"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ovid.com\/10.34067\/KID.0004342020","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T19:57:21Z","timestamp":1786478241000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ovid.com\/10.34067\/KID.0004342020"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,12]]},"references-count":25,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2020]]}},"URL":"https:\/\/doi.org\/10.34067\/kid.0004342020","relation":{},"ISSN":["2641-7650"],"issn-type":[{"value":"2641-7650","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,12]]}}}