Treating resistant hypertension: role of renal denervation Daniel Urban, Sebastian Ewen, Christian Ukena, Dominik Linz, Michael Böhm, Felix Mahfoud Department of Internal Medicine III, Cardiology, Angiology and Intensive Care Medicine, University Hospital of Saarland, Homburg, Saarland, Germany Abstract: Arterial hypertension is the most prevalent risk factor associated with increased cardiovascular morbidity and mortality. Although pharmacological treatment is generally well tolerated, 5%–20% of patients with hypertension are resistant to medical therapy, which is defined as blood pressure above goal (>140/90 mmHg in general; >130–139/80–85 mmHg in patients with diabetes mellitus; >130/80 mmHg in patients with chronic kidney disease) despite treatment with ≥3 antihypertensive drugs of different classes, including a diuretic, at optimal doses. These patients are at significantly higher risk for cardiovascular events, in particular stroke, myocardial infarction, and heart failure, as compared with patients with nonresistant hypertension. The etiology of resistant hypertension is multifactorial and a number of risk factors have been identified. In addition, resistant hypertension might be due to secondary causes such as primary aldosteronism, chronic kidney disease, renal artery stenosis, or obstructive sleep apnea. To identify patients with resistant hypertension, the following must be excluded: pseudo-resistance, which might be due to nonadherence to medical treatment; white-coat effect; and inaccurate measurement technique. Activation of the sympathetic nervous system contributes to the development and maintenance of hypertension by increasing renal renin release, decreasing renal blood flow, and enhancing tubular sodium retention. Catheter-based renal denervation (RDN) is a novel technique specifically targeting renal sympathetic nerves. Clinical trials have demonstrated that RDN significantly reduces blood pressure in patients with resistant hypertension. Experimental studies and small clinical studies indicate that RDN might also have beneficial effects in other diseases and comorbidities, characterized by increased sympathetic activity, such as left ventricular hypertrophy, heart failure, metabolic syndrome and hyperinsulinemia, atrial fibrillation, obstructive sleep apnea, and chronic kidney disease. Further controlled studies are required to investigate the role of RDN beyond blood pressure control. Keywords: resistant hypertension, secondary hypertension, sympathetic nervous system, renal denervation, symplicity