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Poor long-term adherence, therapeutic inertia, polypharmacy, and persistent implementation gaps have generated interest in device-based therapies that provide durable BP reduction, independent of daily medication use. Renal denervation (RDN) has emerged as the most extensively studied catheter-based intervention targeting the sympathetic pathways that contribute to BP regulation. This review summarizes the physiological basis for RDN, including the role of efferent and afferent renal sympathetic pathways in the development and maintenance of hypertension. We review the evolution of RDN technology from first-generation radiofrequency (RF) systems to multielectrode RF, ultrasound-based, and alcohol-mediated platforms, with attention to procedural refinements and lesion patterns over time. We then examine the clinical evidence across major trials, from early open-label studies to modern sham-controlled programs, which now consistently demonstrate modest but clinically meaningful reductions in ABP and OBP with an acceptable safety profile in selected patients. Beyond BP lowering, RDN may have broader biologic effects on cardiac remodeling, neurohormonal activation, inflammation, arrhythmias, metabolic dysfunction, and cardiorenal pathways, although these data remain preliminary, without any evidence from outcome studies. Important knowledge gaps persist, particularly the absence of cardiovascular outcomes trials, variability in treatment response, and the need for improved phenotyping to identify likely responders. As technology, patient selection, and mechanistic understanding continue to advance, RDN may become an increasingly important adjunct in the management of uncontrolled hypertension.<\/jats:p>","DOI":"10.1093\/ajh\/hpag112","type":"journal-article","created":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T11:11:23Z","timestamp":1789384283000},"source":"Crossref","is-referenced-by-count":0,"title":["Renal denervation for hypertension management: past, current evidence, and future directions"],"prefix":"10.1093","author":[{"given":"Shahzad","family":"Hassan","sequence":"first","affiliation":[{"name":"American Heart Association Certified Hypertension Center, Division of Cardiovascular Medicine, University of Miami Healthy System , Miami, FL,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iliana Hurtado","family":"Rendon","sequence":"additional","affiliation":[{"name":"American Heart Association Certified Hypertension Center, Division of Cardiovascular Medicine, University of Miami Healthy System , Miami, FL,","place":["United States"]},{"name":"Miller School of Medicine, University of Miami , Miami, FL,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nikolaos","family":"Spilias","sequence":"additional","affiliation":[{"name":"American Heart Association Certified Hypertension Center, Division of Cardiovascular Medicine, University of Miami Healthy System , Miami, FL,","place":["United States"]},{"name":"Miller School of Medicine, University of Miami , Miami, FL,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Bredel","sequence":"additional","affiliation":[{"name":"College of Arts and Sciences, University of Miami , Miami, FL,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiannis","family":"Chatzizisis","sequence":"additional","affiliation":[{"name":"American Heart Association Certified Hypertension Center, Division of Cardiovascular Medicine, University of Miami Healthy System , Miami, FL,","place":["United States"]},{"name":"Miller School of Medicine, University of Miami , Miami, FL,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Delgado-Lelievre","sequence":"additional","affiliation":[{"name":"American Heart Association Certified Hypertension Center, Division of Cardiovascular Medicine, University of Miami Healthy System , Miami, FL,","place":["United States"]},{"name":"Miller School of Medicine, University of Miami , Miami, FL,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,9,15]]},"reference":[{"key":"2026100106370664800_hpag112-B1","doi-asserted-by":"publisher","first-page":"937","DOI":"10.1016\/S0140-6736(04)17018-9","article-title":"Effect of potentially modifiable risk factors associated with myocardial infarction in 52 countries (the INTERHEART study): case-control study","volume":"364","author":"Yusuf","year":"2004","journal-title":"Lancet"},{"key":"2026100106370664800_hpag112-B2","doi-asserted-by":"publisher","first-page":"795","DOI":"10.1016\/S0140-6736(19)32008-2","article-title":"Modifiable risk factors, cardiovascular disease, and mortality in 155 722 individuals from 21 high-income, middle-income, and low-income countries (PURE): a prospective cohort study","volume":"395","author":"Yusuf","year":"2020","journal-title":"Lancet"},{"key":"2026100106370664800_hpag112-B3","doi-asserted-by":"publisher","first-page":"1923","DOI":"10.1016\/S0140-6736(18)32225-6","article-title":"Global, regional, and national comparative risk assessment of 84 behavioural, environmental and occupational, and metabolic risks or clusters of risks for 195 countries and territories, 1990\u20132017: a systematic analysis for the Global Burden of Disease Study 2017","volume":"392","author":"Stanaway","year":"2018","journal-title":"The Lancet"},{"key":"2026100106370664800_hpag112-B4","doi-asserted-by":"publisher","first-page":"223","DOI":"10.1038\/s41581-019-0244-2","article-title":"The global epidemiology of hypertension","volume":"16","author":"Mills","year":"2020","journal-title":"Nat Rev Nephrol"},{"key":"2026100106370664800_hpag112-B5","author":"Global report on hypertension: the race against a silent killer","year":"2025"},{"key":"2026100106370664800_hpag112-B6","doi-asserted-by":"publisher","first-page":"1273","DOI":"10.1056\/NEJMoa2206916","article-title":"The Global Cardiovascular Risk Consortium. 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