{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T03:40:46Z","timestamp":1792726846767,"version":"4.5.0"},"reference-count":57,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T00:00:00Z","timestamp":1792627200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T00:00:00Z","timestamp":1792627200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["dom-pubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Diabetes Obesity Metabolism"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Autonomic dysfunction increases the risk of cardio\u2010kidney\u2010metabolic (CKM) syndrome including metabolic dysfunction\u2010associated steatotic liver disease (MASLD), type 2 diabetes (T2D), cardiovascular disease (CVD) and chronic kidney disease (CKD). Renal denervation reduces renal sympathetic nerve activity and lowers blood pressure independent of long\u2010term pharmacotherapy, with potential downstream effects on metabolic and hepatic pathways. We aimed to evaluate the impact of renal denervation, compared with intensive antihypertensive therapy, on cardiometabolic disease risk.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We conducted a target trial emulation using the TriNetX global federated health research network. Eligible participants were adults with hypertension (ICD\u201010 code I10) who were treated with either\n                      <jats:italic>renal denervation therapy and pharmacological treatment<\/jats:italic>\n                      (identified via ICD\u201010 or Current Procedural Terminology codes), acting as the treatment group, or an\n                      <jats:italic>intensive pharmacological antihypertensive regime<\/jats:italic>\n                      (four of a beta blocker, calcium channel blocker, angiotensin\u2010converting enzyme inhibitor, angiotensin II receptor blocker, alpha blocker or diuretic), acting as the control group. Propensity score matching (1:1) balanced the treatment and control groups, accounting for confounding variables. The\n                      <jats:italic>primary outcome<\/jats:italic>\n                      was of MASLD\/metabolic dysfunction\u2010associated steatohepatitis (MASH), while secondary outcomes included T2D, CKD and a composite of major adverse cardiovascular events (MACE): sudden cardiac death, ischaemic heart disease (IHD), cerebrovascular accident (CVA), peripheral vascular disease (PVD) and heart failure (HF). Cox regression generated hazard ratios (HRs) and 95% confidence intervals (CIs).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>After matching, 1735 patients remained in each group, with well\u2010balanced baseline characteristics (mean age 42 vs. 41\u2009years; standardised mean difference [SMD] 0.05; 52.6% vs. 54.3% male; SMD 0.03). After PSM, renal denervation was associated with a lower risk of MASLD (HR 0.38 [0.29, 0.51]), T2D (HR 0.21 [0.13, 0.33]), CKD (HR 0.26 [0.20, 0.35]), MACE (HR 0.46 [0.34, 0.62]), IHD (HR 0.56 [0.39, 0.80]), CVA (HR 0.33 [0.20, 0.52]) and HF (HR 0.39 [0.25, 0.62]).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Control of the sympathetic nervous system with renal denervation therapy in patients with resistant hypertension is associated with a lower risk of incident CKM syndrome including MASLD, T2D, CVD and CKD, supporting the role of autonomic dysfunction in the progression of cardiometabolic disease.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/dom.71421","type":"journal-article","created":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T03:26:58Z","timestamp":1792726018000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Reduced Risk of\n                    <scp>MASLD<\/scp>\n                    and Cardiometabolic Disease Following Renal Denervation Therapy in Patients With Resistant Hypertension"],"prefix":"10.1111","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8066-9470","authenticated-orcid":false,"given":"Alex E.","family":"Henney","sequence":"first","affiliation":[{"name":"Department of Cardiovascular and Metabolic Medicine University of Liverpool  Liverpool UK"},{"name":"Metabolism and Nutrition Research Group Liverpool University Hospitals NHS Foundation Trust  Liverpool Merseyside UK"},{"name":"Liverpool Centre for Cardiovascular Sciences at University of Liverpool Liverpool John Moores University, and Liverpool University Hospitals NHS Foundation Trust  Liverpool Merseyside UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9991-7369","authenticated-orcid":false,"given":"Matthew","family":"Anson","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular and Metabolic Medicine University of Liverpool  Liverpool UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David R.","family":"Riley","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular and Metabolic Medicine University of Liverpool  Liverpool UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurent","family":"Fauchier","sequence":"additional","affiliation":[{"name":"Service de Cardiologie, Centre Hospitalier Universitaire Trousseau et Facult\u00e9 de M\u00e9decine Universit\u00e9 Fran\u00e7ois Rabelais  Tours France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joel P.","family":"Giblett","sequence":"additional","affiliation":[{"name":"Liverpool Centre for Cardiovascular Sciences at University of Liverpool Liverpool John Moores University, and Liverpool University Hospitals NHS Foundation Trust  Liverpool Merseyside UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7566-1626","authenticated-orcid":false,"given":"Gregory Y. H.","family":"Lip","sequence":"additional","affiliation":[{"name":"Liverpool Centre for Cardiovascular Sciences at University of Liverpool Liverpool John Moores University, and Liverpool University Hospitals NHS Foundation Trust  Liverpool Merseyside UK"},{"name":"Department of Clinical Medicine Aalborg University  Aalborg Denmark"},{"name":"Department of Cardiology Lipidology and Internal Medicine With Intensive Coronary Care Unit, Medical University of Bialystok  Bialystok Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7188-8903","authenticated-orcid":false,"given":"Rayaz A.","family":"Malik","sequence":"additional","affiliation":[{"name":"Division of Research, Weill Cornell Medicine  Doha Qatar"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel J.","family":"Cuthbertson","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular and Metabolic Medicine University of Liverpool  Liverpool UK"},{"name":"Metabolism and Nutrition Research Group Liverpool University Hospitals NHS Foundation Trust  Liverpool Merseyside UK"},{"name":"Liverpool Centre for Cardiovascular Sciences at University of Liverpool Liverpool John Moores University, and Liverpool University Hospitals NHS Foundation Trust  Liverpool Merseyside UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Uazman","family":"Alam","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular and Metabolic Medicine University of Liverpool  Liverpool UK"},{"name":"Metabolism and Nutrition Research Group Liverpool University Hospitals NHS Foundation Trust  Liverpool Merseyside UK"},{"name":"Liverpool Centre for Cardiovascular Sciences at University of Liverpool Liverpool John Moores University, and Liverpool University Hospitals NHS Foundation Trust  Liverpool Merseyside UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,10,22]]},"reference":[{"issue":"10258","key":"e_1_2_10_2_1","doi-asserted-by":"crossref","first-page":"1223","DOI":"10.1016\/S0140-6736(20)30752-2","article-title":"Global Burden of 87 Risk Factors in 204 Countries and Territories, 1990\u20102019: A Systematic Analysis for the Global Burden of Disease Study 2019","volume":"396","year":"2020","journal-title":"Lancet"},{"issue":"20","key":"e_1_2_10_3_1","doi-asserted-by":"crossref","first-page":"1606","DOI":"10.1161\/CIR.0000000000001184","article-title":"Cardiovascular\u2010Kidney\u2010Metabolic Health: A Presidential Advisory From the American Heart Association","volume":"148","author":"Ndumele C. 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Y.","year":"2021","journal-title":"Journal of Diabetes Investigation"},{"issue":"16","key":"e_1_2_10_10_1","first-page":"8458","article-title":"Autonomic Dysfunction in Kidney Diseases","volume":"24","author":"Lai S.","year":"2020","journal-title":"European Review for Medical and Pharmacological Sciences"},{"issue":"1","key":"e_1_2_10_11_1","doi-asserted-by":"crossref","first-page":"28076","DOI":"10.1038\/s41598-025-13758-x","article-title":"Association Between Autonomic Dysfunction and Arterial Stiffness in Hypertensive Patients","volume":"15","author":"Wang J.","year":"2025","journal-title":"Scientific Reports"},{"issue":"17","key":"e_1_2_10_12_1","doi-asserted-by":"crossref","first-page":"4565","DOI":"10.1113\/JP277994","article-title":"Liver Sympathetic Denervation Reverses Obesity\u2010Induced Hepatic Steatosis","volume":"597","author":"Hurr C.","year":"2019","journal-title":"Journal of Physiology"},{"issue":"10234","key":"e_1_2_10_13_1","doi-asserted-by":"crossref","first-page":"1444","DOI":"10.1016\/S0140-6736(20)30554-7","article-title":"Efficacy of Catheter\u2010Based Renal Denervation in the Absence of Antihypertensive Medications (SPYRAL HTN\u2010OFF MED Pivotal): A Multicentre, Randomised, Sham\u2010Controlled Trial","volume":"395","author":"B\u00f6hm M.","year":"2020","journal-title":"Lancet"},{"issue":"10137","key":"e_1_2_10_14_1","doi-asserted-by":"crossref","first-page":"2346","DOI":"10.1016\/S0140-6736(18)30951-6","article-title":"Effect of Renal Denervation on Blood Pressure in the Presence of Antihypertensive Drugs: 6\u2010Month Efficacy and Safety Results From the SPYRAL HTN\u2010ON MED Proof\u2010of\u2010Concept Randomised Trial","volume":"391","author":"Kandzari D. E.","year":"2018","journal-title":"Lancet"},{"issue":"10137","key":"e_1_2_10_15_1","doi-asserted-by":"crossref","first-page":"2335","DOI":"10.1016\/S0140-6736(18)31082-1","article-title":"Endovascular Ultrasound Renal Denervation to Treat Hypertension (RADIANCE\u2010HTN SOLO): A Multicentre, International, Single\u2010Blind, Randomised, Sham\u2010Controlled Trial","volume":"391","author":"Azizi M.","year":"2018","journal-title":"Lancet"},{"issue":"10293","key":"e_1_2_10_16_1","doi-asserted-by":"crossref","first-page":"2476","DOI":"10.1016\/S0140-6736(21)00788-1","article-title":"Ultrasound Renal Denervation for Hypertension Resistant to a Triple Medication Pill (RADIANCE\u2010HTN TRIO): A Randomised, Multicentre, Single\u2010Blind, Sham\u2010Controlled Trial","volume":"397","author":"Azizi M.","year":"2021","journal-title":"Lancet"},{"issue":"12","key":"e_1_2_10_17_1","doi-asserted-by":"crossref","first-page":"1874","DOI":"10.1097\/HJH.0000000000003480","article-title":"2023 ESH Guidelines for the Management of Arterial Hypertension the Task Force for the Management of Arterial Hypertension of the European Society of Hypertension: Endorsed by the International Society of Hypertension (ISH) and the European Renal Association (ERA)","volume":"41","author":"Mancia G.","year":"2023","journal-title":"Journal of Hypertension"},{"issue":"10","key":"e_1_2_10_18_1","doi-asserted-by":"crossref","first-page":"e135","DOI":"10.1161\/HYP.0000000000000240","article-title":"Renal Denervation for the Treatment of Hypertension: A Scientific Statement From the American Heart Association","volume":"81","author":"Cluett J. L.","year":"2024","journal-title":"Hypertension"},{"key":"e_1_2_10_19_1","doi-asserted-by":"crossref","first-page":"974","DOI":"10.1136\/heartjnl-2025-327110","article-title":"Renal Denervation for Hypertension Management in the UK: A Delphi Expert Consensus","volume":"112","author":"Haworth P. A. J.","year":"2025","journal-title":"Heart"},{"key":"e_1_2_10_20_1","doi-asserted-by":"crossref","DOI":"10.3389\/fphys.2012.00010","article-title":"Effects of Renal Denervation on Sympathetic Activation, Blood Pressure, and Glucose Metabolism in Patients With Resistant Hypertension","volume":"3","author":"Schlaich M. 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L.","year":"2014","journal-title":"New England Journal of Medicine"},{"issue":"7624","key":"e_1_2_10_24_1","doi-asserted-by":"crossref","first-page":"806","DOI":"10.1136\/bmj.39335.541782.AD","article-title":"Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) Statement: Guidelines for Reporting Observational Studies","volume":"335","author":"Elm E.","year":"2007","journal-title":"BMJ"},{"issue":"4","key":"e_1_2_10_25_1","doi-asserted-by":"crossref","first-page":"268","DOI":"10.7326\/M16-2607","article-title":"Sensitivity Analysis in Observational Research: Introducing the E\u2010Value","volume":"167","author":"VanderWeele T. 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D.","year":"2010","journal-title":"Lancet"},{"issue":"9671","key":"e_1_2_10_27_1","doi-asserted-by":"crossref","first-page":"1275","DOI":"10.1016\/S0140-6736(09)60566-3","article-title":"Catheter\u2010Based Renal Sympathetic Denervation for Resistant Hypertension: A Multicentre Safety and Proof\u2010Of\u2010Principle Cohort Study","volume":"373","author":"Krum H.","year":"2009","journal-title":"Lancet"},{"issue":"9917","key":"e_1_2_10_28_1","doi-asserted-by":"crossref","first-page":"622","DOI":"10.1016\/S0140-6736(13)62192-3","article-title":"Percutaneous Renal Denervation in Patients With Treatment\u2010Resistant Hypertension: Final 3\u2010Year Report of the Symplicity HTN\u20101 Study","volume":"383","author":"Krum H.","year":"2014","journal-title":"Lancet"},{"issue":"10333","key":"e_1_2_10_29_1","doi-asserted-by":"crossref","first-page":"1401","DOI":"10.1016\/S0140-6736(22)00455-X","article-title":"Long\u2010Term Efficacy and Safety of Renal Denervation in the Presence of Antihypertensive Drugs (SPYRAL HTN\u2010ON MED): A Randomised, Sham\u2010Controlled Trial","volume":"399","author":"Mahfoud F.","year":"2022","journal-title":"Lancet"},{"issue":"10108","key":"e_1_2_10_30_1","doi-asserted-by":"crossref","first-page":"2160","DOI":"10.1016\/S0140-6736(17)32281-X","article-title":"Catheter\u2010Based Renal Denervation in Patients With Uncontrolled Hypertension in the Absence of Antihypertensive Medications (SPYRAL HTN\u2010OFF MED): A Randomised, Sham\u2010Controlled, Proof\u2010Of\u2010Concept Trial","volume":"390","author":"Townsend R. R.","year":"2017","journal-title":"Lancet"},{"issue":"8","key":"e_1_2_10_31_1","doi-asserted-by":"crossref","first-page":"651","DOI":"10.1001\/jama.2023.0713","article-title":"Endovascular Ultrasound Renal Denervation to Treat Hypertension: The RADIANCE II Randomized Clinical Trial","volume":"329","author":"Azizi M.","year":"2023","journal-title":"Journal of the American Medical Association"},{"issue":"18","key":"e_1_2_10_32_1","doi-asserted-by":"crossref","first-page":"1940","DOI":"10.1161\/CIRCULATIONAHA.110.991869","article-title":"Effect of Renal Sympathetic Denervation on Glucose Metabolism in Patients With Resistant Hypertension: A Pilot Study","volume":"123","author":"Mahfoud F.","year":"2011","journal-title":"Circulation"},{"key":"e_1_2_10_33_1","doi-asserted-by":"crossref","DOI":"10.1155\/2017\/6915310","article-title":"Effects of Renal Denervation on Insulin Sensitivity and Inflammatory Markers in Nondiabetic Patients With Treatment\u2010Resistant Hypertension","volume":"2017","author":"Kampmann U.","year":"2017","journal-title":"Journal of Diabetes Research"},{"key":"e_1_2_10_34_1","doi-asserted-by":"crossref","DOI":"10.3389\/fphys.2017.00369","article-title":"The Effect of Renal Denervation on Plasma Adipokine Profile in Patients With Treatment Resistant Hypertension","volume":"8","author":"Eikelis N.","year":"2017","journal-title":"Frontiers in Physiology"},{"issue":"7","key":"e_1_2_10_35_1","doi-asserted-by":"crossref","DOI":"10.1093\/ckj\/sfaf184","article-title":"Effect of Renal Denervation on Glucose Metabolism in Hypertensive Patients With and Without Chronic Kidney Disease","volume":"18","author":"Bytyqi V.","year":"2025","journal-title":"Clinical Kidney Journal"},{"issue":"4","key":"e_1_2_10_36_1","doi-asserted-by":"crossref","first-page":"1503","DOI":"10.1016\/j.clnu.2021.02.027","article-title":"Metabolic Effects Two Years After Renal Denervation in Insulin Resistant Hypertensive Patients. The re\u2010Shape CV\u2010Risk Study","volume":"40","author":"Miroslawska A. K.","year":"2021","journal-title":"Clinical Nutrition"},{"issue":"4","key":"e_1_2_10_37_1","doi-asserted-by":"crossref","first-page":"751","DOI":"10.1161\/HYPERTENSIONAHA.114.04798","article-title":"Denervation of the Renal Arteries in Metabolic Syndrome","volume":"65","author":"Verloop W. L.","year":"2015","journal-title":"Hypertension"},{"issue":"8","key":"e_1_2_10_38_1","doi-asserted-by":"crossref","first-page":"2164","DOI":"10.2337\/db16-0205","article-title":"Renal Denervation for Resistant Hypertension Fails to Improve Insulin Resistance as Assessed by Hyperinsulinemic\u2010Euglycemic Step Clamp","volume":"65","author":"Miroslawska A. 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