{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T16:08:36Z","timestamp":1793203716621,"version":"4.5.0"},"reference-count":48,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"15","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2025,8,5]]},"abstract":"<jats:sec xml:lang=\"en\">\n            <jats:title>Background<\/jats:title>\n            <jats:p xml:lang=\"en\">Chronic kidney disease (CKD) is an independent cardiovascular risk factor. Patients with CKD develop uremic cardiomyopathy characterized by activation of the sympathetic nervous system, left ventricular hypertrophy, and accumulation of uremic toxins such as indoxyl sulfate (IS). The aim of this study was to assess the effects of renal denervation (RDN) on uremic cardiomyopathy in a rat model of CKD.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Methods<\/jats:title>\n            <jats:p xml:lang=\"en\">Sprague\u2013Dawley rats were fed a standard chow (control group, n=6) or a 0.25% adenine\u2010enriched chow (n=16) for 16\u2009weeks to induce CKD. After 4\u2009weeks, CKD rats with CKD were subjected to bilateral RDN (AD\u2010RDN, n=8) or to sham operation (AD, n=8). Blood pressure measurements, echocardiography, and cardiac magnetic resonance imaging were deployed during the experiment. Left ventricular hypertrophy was evaluated histologically. IS was measured using ELISA. In H9C2 cardiomyoblasts, the hypertrophic effects of IS were characterized in\u00a0vitro.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Results<\/jats:title>\n            <jats:p xml:lang=\"en\">\n              In AD rats, left ventricular septal wall thickness (2.37\u00b10.036 versus 1.91\u00b10.014\u2009mm in CTRL,\n              <jats:italic toggle=\"no\">P<\/jats:italic>\n              &lt;0.0001), E\/A ratio, and cardiomyocyte size were significantly increased. Following RDN, left ventricular wall thickness (\n              <jats:italic toggle=\"no\">P<\/jats:italic>\n              &lt;0.0001 versus AD), E\/A ratio (\n              <jats:italic toggle=\"no\">P<\/jats:italic>\n              &lt;0.0001 versus AD), and myocyte hypertrophy were significantly reduced. Plasma IS was increased in AD (0.79\u00b10.07 versus 0.2\u00b10.12\u2009\u03bcg\/mg in the control group,\n              <jats:italic toggle=\"no\">P<\/jats:italic>\n              =0.0044) and reduced in AD\u2010RDN (\n              <jats:italic toggle=\"no\">P<\/jats:italic>\n              =0.0073 versus AD). Urinary IS remained unchanged after RDN, whereas hepatic concentration of IS decreased after RDN (\n              <jats:italic toggle=\"no\">P<\/jats:italic>\n              =0.023). Plasma IS correlated with left ventricular hypertrophy (r=0.779,\n              <jats:italic toggle=\"no\">P<\/jats:italic>\n              &lt;0.0001). Stimulation of H9C2 cardiomyoblasts with IS or serum from AD rats showed an increase in cell size (\n              <jats:italic toggle=\"no\">P<\/jats:italic>\n              =0.0015), whereas AD\u2010RDN serum showed no effect.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p xml:lang=\"en\">In a rat model of CKD, improved cardiac function following RDN was associated with reduced plasma concentrations of IS. To the present, IS remains a persistent clinical concern in patients with CKD due to its inefficient removal by conventional hemodialysis and its significant role in promoting both kidney and myocardial disease. Thus, RDN may ameliorate uremic cardiomyopathy by reducing IS and potentially represents a treatment option for patients with CKD and cardiovascular disease. Clinical trials are warranted to investigate the effects of RDN on cardiovascular outcomes in patients with CKD.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/jaha.124.038785","type":"journal-article","created":{"date-parts":[[2025,7,21]],"date-time":"2025-07-21T12:13:31Z","timestamp":1753100011000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":2,"title":["Renal Denervation Improves Uremic Cardiomyopathy in Rats With Chronic Kidney Disease"],"prefix":"10.1161","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-5043-8520","authenticated-orcid":false,"given":"Philipp","family":"Markwirth","sequence":"first","affiliation":[{"name":"Universit\u00e4t des Saarlandes","place":["Homburg, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5080-1960","authenticated-orcid":false,"given":"Simina\u2010Ramona","family":"Selejan","sequence":"additional","affiliation":[{"name":"Universit\u00e4t des Saarlandes","place":["Homburg, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6946-9825","authenticated-orcid":false,"given":"Mathias","family":"Hohl","sequence":"additional","affiliation":[{"name":"Universit\u00e4t des Saarlandes","place":["Homburg, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan J.","family":"Schunk","sequence":"additional","affiliation":[{"name":"Universit\u00e4t des Saarlandes","place":["Homburg, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0924-3490","authenticated-orcid":false,"given":"Andreas","family":"M\u00fcller","sequence":"additional","affiliation":[{"name":"Universit\u00e4t des Saarlandes","place":["Homburg, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4558-4041","authenticated-orcid":false,"given":"Stefan","family":"Wagenpfeil","sequence":"additional","affiliation":[{"name":"Saarland University","place":["Homburg\/Saar, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7470-7912","authenticated-orcid":false,"given":"Lea","family":"Wagmann","sequence":"additional","affiliation":[{"name":"Institute of Experimental and Clinical Pharmacology and Toxicology, Saarland University","place":["Homburg, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florian","family":"Kahles","sequence":"additional","affiliation":[{"name":"RWTH Aachen University","place":["Aachen, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-6059-1671","authenticated-orcid":false,"given":"Mert","family":"Tokcan","sequence":"additional","affiliation":[{"name":"Universit\u00e4t des Saarlandes","place":["Homburg, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Markus","family":"Therre","sequence":"additional","affiliation":[{"name":"Universit\u00e4t des Saarlandes","place":["Homburg, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5771-6278","authenticated-orcid":false,"given":"Emiel P. 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