Use Of Renal Denervation Research Articles

Renal denervation in a patient with Alport syndrome and rejected renal allograft

Renal denervation is a new intervention to treat resistant hypertension. By applying radiofrequency (RF) to renal arteries, sympathetic nerves in adventitia layer of vascular wall can be denervated. Sympathetic hyperactivity is an important contributory factor in hypertension of hemodialysis patients. Hyperactive sympathetic nervous system aggravates hypertension and it can cause complications like left ventricular hypertrophy, heart failure, arrhythmias and atherogenesis. Our report illustrates the use of renal denervation using conventional RF catheter for uncontrolled hypertension in a patient with Alport syndrome and rejected renal allograft. Progressive and sustained reduction of blood pressure was obtained post-procedure and at 24 months follow-up with antihypertensives decreased from 6 to 2 per day, thereby demonstrating the safety, feasibility, and efficacy of the procedure. There are some reports available on the usefulness of this technique in hemodialysis patients; however, there are no studies of renal denervation in patients with Alport syndrome and failed allograft situation.

Increased Sympathetic Renal Innervation in Hemodialysis Patients Is the Anatomical Substrate of Sympathetic Hyperactivity in End-Stage Renal Disease.

BackgroundRenal denervation represents an emerging treatment for resistant hypertension in patients with end‐stage renal disease, but data about the anatomic substrate of this treatment are lacking. Therefore, the aim of this study was to investigate the morphological basis of sympathetic hyperactivity in the setting of hemodialysis patients to identify an anatomical substrate that could warrant the use of this new therapeutic approach.Methods and ResultsThe distribution of sympathetic nerves was evaluated in the adventitia of 38 renal arteries that were collected at autopsy or during surgery from 25 patients: 9 with end‐stage renal disease on dialysis (DIAL group) and 16 age‐matched control nondialysis patients (CTRL group). Patients in the DIAL group showed a significant increase in nerve density in the internal area of the peri‐adventitial tissue (within the first 0.5 mm of the beginning of the adventitia) compared with the CTRL group (4.01±0.30 versus 2.87±0.28×mm2, P=0.01). Regardless of dialysis, hypertensive patients with signs of severe arteriolar damage had a greater number of nerve endings in the most internal adventitia, and this number was significantly higher than in patients without hypertensive arteriolar damage (3.90±0.36 versus 2.87±0.41×mm2, P=0.04), showing a correlation with hypertensive arteriolar damage rather than with hypertensive clinical history.ConclusionsThe findings from this study provide a morphological basis underlying sympathetic hyperactivity in patients with end‐stage renal disease and might offer useful information to improve the use of renal denervation in this group of patients.

Spanish Cardiac Catheterization and Coronary Intervention Registry. 24th Official Report of the Spanish Society of Cardiology Working Group on Cardiac Catheterization and Interventional Cardiology (1990-2014)

Introduction and objectivesThe Working Group on Cardiac Catheterization and Interventional Cardiology presents its annual report on the data from the registry of the activity in Spain in 2014. MethodsData were voluntarily provided by participating centers. The information was introduced online and was analyzed by the Steering Committee of the Working Group on Cardiac Catheterization and Interventional Cardiology. ResultsData were reported by 106 hospitals. A total of 140 461 diagnostic procedures (125 484 coronary angiograms) were performed, representing a rate of 3014 diagnostic studies per million population. This year, the number of percutaneous coronary interventions increased to 67 611, giving a rate of 1447 interventions per million population. A total of 94 458 stents were implanted, including 64 057 drug-eluting stents and 2424 biodegradable intracoronary devices. Of the total number of percutaneous coronary interventions, 17 825 were in acute myocardial infarction, representing 26.4% of all coronary interventions. A radial approach was used in 74% of diagnostic procedures and in 70.4% of interventional procedures. The use of renal denervation decreased, whereas over 125 mitral leak closures were performed. Transcatheter aortic valve implantation procedures exceeded 1300 implantations per year, a 27% increase from 2013. ConclusionsThe registry for 2014 shows a slight increase in coronary disease activity despite no increase in the management of ST-segment elevation myocardial infarction. Drug-eluting intracoronary devices now comprise over 70% of all intracoronary devices. A continual increase is only seen in certain structural interventional techniques, such as transcatheter aortic valve implantation and perivalvular leak closure.

Registro Español de Hemodinámica y Cardiología Intervencionista. XXIV Informe Oficial de la Sección de Hemodinámica y Cardiología Intervencionista de la Sociedad Española de Cardiología (1990-2014)

Introduction and objectivesThe Working Group on Cardiac Catheterization and Interventional Cardiology presents its annual report on the data from the registry of the activity in Spain in 2014. MethodsData were voluntarily provided by participating centers. The information was introduced online and was analyzed by the Steering Committee of the Working Group on Cardiac Catheterization and Interventional Cardiology. ResultsData were reported by 106 hospitals. A total of 140 461 diagnostic procedures (125 484 coronary angiograms) were performed, representing a rate of 3014 diagnostic studies per million population. This year, the number of percutaneous coronary interventions increased to 67 611, giving a rate of 1447 interventions per million population. A total of 94 458 stents were implanted, including 64 057 drug-eluting stents and 2424 biodegradable intracoronary devices. Of the total number of percutaneous coronary interventions, 17 825 were in acute myocardial infarction, representing 26.4% of all coronary interventions. A radial approach was used in 74% of diagnostic procedures and in 70.4% of interventional procedures. The use of renal denervation decreased, whereas over 125 mitral leak closures were performed. Transcatheter aortic valve implantation procedures exceeded 1300 implantations per year, a 27% increase from 2013. ConclusionsThe registry for 2014 shows a slight increase in coronary disease activity despite no increase in the management of ST-segment elevation myocardial infarction. Drug-eluting intracoronary devices now comprise over 70% of all intracoronary devices. A continual increase is only seen in certain structural interventional techniques, such as transcatheter aortic valve implantation and perivalvular leak closure.Full English text available from: www.revespcardiol.org/en

Device-based approaches for renal nerve ablation for hypertension and beyond.

Animal and human studies have demonstrated that chronic activation of renal sympathetic nerves is critical in the pathogenesis and perpetuation of treatment-resistant hypertension. Bilateral renal denervation has emerged as a safe and effective, non-pharmacological treatment for resistant hypertension that involves the selective ablation of efferent and afferent renal nerves to lower blood pressure. However, the most recent and largest randomized controlled trial failed to confirm the primacy of renal denervation over a sham procedure, prompting widespread re-evaluation of the therapy's efficacy. Disrupting renal afferent sympathetic signaling to the hypothalamus with renal denervation lowers central sympathetic tone, which has the potential to confer additional clinical benefits beyond blood pressure control. Specifically, there has been substantial interest in the use of renal denervation as either a primary or adjunct therapy in pathological conditions characterized by central sympathetic overactivity such as renal disease, heart failure and metabolic-associated disorders. Recent findings from pre-clinical and proof-of-concept studies appear promising with renal denervation shown to confer cardiovascular and metabolic benefits, largely independent of changes in blood pressure. This review explores the pathological rationale for targeting sympathetic renal nerves for blood pressure control. Latest developments in renal nerve ablation modalities designed to improve procedural success are discussed along with prospective findings on the efficacy of renal denervation to lower blood pressure in treatment-resistant hypertensive patients. Preliminary evidence in support of renal denervation as a possible therapeutic option in disease states characterized by central sympathetic overactivity is also presented.

Activation of afferent renal nerves modulates RVLM-projecting PVN neurons.

Renal denervation for the treatment of hypertension has proven to be successful; however, the underlying mechanism/s are not entirely clear. To determine if preautonomic neurons in the paraventricular nucleus (PVN) respond to afferent renal nerve (ARN) stimulation, extracellular single-unit recording was used to investigate the contribution of the rostral ventrolateral medulla (RVLM)-projecting PVN (PVN-RVLM) neurons to the response elicited during stimulation of ARN. In 109 spontaneously active neurons recorded in the PVN of anesthetized rats, 25 units were antidromically activated from the RVLM. Among these PVN-RVLM neurons, 84% (21/25) were activated by ARN stimulation. The baseline discharge rate was significantly higher in these neurons than those PVN-RVLM neurons not activated by ARN stimulation (16%, 4/25). The responsiveness of these neurons to baroreflex activation induced by phenylephrine and activation of cardiac sympathetic afferent reflex (CSAR) was also examined. Almost all of the PVN neurons that responded to ARN stimulation were sensitive to baroreflex (95%) and CSAR (100%). The discharge characteristics for nonevoked neurons (not activated by RVLM antidromic stimulation) showed that 23% of these PVN neurons responded to ARN stimulation. All the PVN neurons that responded to ARN stimulation were activated by N-methyl-D-aspartate, and these responses were attenuated by the glutamate receptor blocker AP5. These experiments demonstrated that sensory information originating in the kidney is integrated at the level of preautonomic neurons within the PVN, providing a novel mechanistic insight for use of renal denervation in the modulation of sympathetic outflow in disease states such as hypertension and heart failure.

Renal denervation: unde venis et quo vadis?

Renal denervation is a minimally invasive, catheter-based option for the treatment of refractory hypertension. Indications and contraindications for renal denervation have been defined in an interdisciplinary manner. The efficacy and safety of the procedure were evaluated. Currently, indication for renal denervation is limited to patients with primary hypertension and a systolic blood pressure of ≥ 160 mm Hg (or ≥ 150 mm Hg in diabetes type 2) despite optimal medical therapy with ≥ 3 different antihypertensive drugs. In this specific patient population, an average blood pressure reduction of 32/14 mmHg was observed in non-randomized/-controlled trials after renal denervation. These results were not confirmed in the first randomized controlled trial with a non-significantly superior blood pressure reduction of 14.1 ± 23.9 mm Hg compared to controls (-11.74 ± 25.94 mm Hg, difference -2.39 mm Hg p = 0.26 for superiority with a margin of 5 mm Hg) who underwent a sham procedure. The efficacy and long-term effects of renal denervation need to be re-evaluated in light of the HTN3 study results. To date, renal denervation should not be performed outside of clinical trials. Future trials should also assess if renal denervation can be performed with sufficient safety and efficacy in patients with hypertension-associated diseases. The use of renal denervation as an alternative therapy (e. g. in patients with drug intolerance) can currently not be advocated. The indication for renal denervation should be assessed in an interdisciplinary fashion and according to current guidelines with a special focus on ruling out secondary causes for arterial hypertension. 5 - 10 % of patients with hypertension suffer from refractory hypertension, but only about 1 % of patients meet the criteria for a renal denervation. Renal denervation leads to a significant decrease in office blood pressure; however, the impact on 24-hour blood pressure measurements remains unclear. In the first randomized controlled trial on renal denervation with a control group undergoing a sham procedure, blood pressure reduction failed to reach the anticipated level of superiority over best medical treatment. Periprocedural complications are rare, but long-term safety can currently not be appraised due to the limited data available.

Pathophysiology of resistant hypertension in chronic kidney disease.

Hypertension associated with chronic kidney diseases often is resistant to drug treatment. This review deals with two main aspects of the management of CKD patients with hypertension: the role of sodium/volume and the need for dietary salt restriction, as well as appropriate use of diuretics and what currently is called sequential nephron blockade; the second aspect that is addressed extensively in this review is the role of the sympathetic nervous system and the possible clinical use of renal denervation.

The link between renal denervation and reduction of cardiovascular risks: Simplicity or not?

It has been demonstrated that abnormalities of the sympathetic nervous system strongly contribute to the development and/or maintenance of multiple disease states such as hypertension, heart failure, diabetes mellitus, sleep apnea, kidney disease and arrhythmias [1]. When we look through the window of hypertension, the renal nerves have been identified as important contributors in both development and maintenance of hypertension [2]. We read with great enthusiasm the article written by Ott and colleagues evaluating the effect of renal denervation (RDN) on elevated urinary albumin-to-creatinine ratio (UACR) in patients with resistant hypertension [3]. They have subdivided the patients according to their UACR at baseline into micro(30–300 mg/g, n = 37) and macroalbuminuria (300–2200 mg/g, n = 22) and found a significant reduction in UACR in all patients (p b 0.001) and in both subgroups (p b 0.001). They have implicated that, following RDN, the magnitude of albuminuria as well as the prevalence of microand macroalbuminuria decreased in patients with treatment-resistant hypertension and concluded that, since albuminuria is an independent renal and cardiovascular risk factor, a reduction of renal and cardiovascular risk could be achieved by RDN in these patients. The effect of catheter-based RDN on resistant hypertension in humans was assessed clinically in 2009, by the first proof-of-principle multicenter study from 45 patients with treatment-resistant hypertension [4]. The initial cohort was subsequently expanded from 45 to 153 patients, and the follow-up durationwas increased to a minimum of 2 years (Symplicity HTN-1) [5]. Both studies reported promising results favoring RDN. As it was an unblinded prospective cohort study without a control group, it was soon followed by the Symplicity HTN-2 trial to further assess RDN in a randomized fashion [6]. The Symplicity HTN-2 included 106 patients with severe resistant hypertensionwhowere randomized to RDN and conventional medical therapy versus conventional medical therapy alone. RDN was found to bemore effective thanmedical therapy alone in reducing blood pressure (BP), causing a reduction of 32 mmHg in systolic and 12 mm Hg in diastolic BP in the RDN group and no significant change in the control group. However, no changes in renal function or UACRwere identified in either group. The studywasdesigned such that patients from the control group were allowed to crossover to RDN therapy after six months, provided that the BP remained uncontrolled with a systolic BP greater than 160mmHg. Interestingly, the crossover group consisting of 35 patients experienced a significant drop in BP similar to that observed in the initial RDN group at 6 months' follow-up [7]. Recently published long-term results of the Symplicity HTN-1 study also imply that the efficacy gradually increases in 3 years' follow-up [7]. There is also evidence that patients with milder forms of hypertension may benefit from RDN [8]. Furthermore, there is emerging evidence that RDN may have a role in the treatment of heart failure, obstructive sleep apnea, insulin resistance, atrial fibrillation, hypertension associatedwith end-stage renal disease and, as shown recently, even in patients with ventricular storm where sympathetic nervous system seems to have a crucial role [9–13]. Thus, given the fact that resistant hypertension and other diseases associated with elevated sympathetic tone have significant morbidity and mortality rates, RDN therapy might be expected to have a crucial role on public health. However, the results of the Symplicity-3 trial overturned this optimistic mood about the RDN [14]. In the Symplicity HTN-3 study, RDN had no significant effect on office or 24-hour ambulatory systolic BP, findings that contradict most published studies on RDN. A recent trial even suggested inferiority of RDN as compared to adjusted drug treatment [15]. There is now growing evidence of lack of BP response following RDN in up to 50% of cases in some reports [16,17]. Clinical use of RDN had significantly increased after the encouraging results of Symplicity HTN-1 trial [5]. Afterwards, clinical studies with encouraging results appeared in the literature [18–20]. Parallel to these developments, medical device companies fancied RDN as the next big innovation and as a blockbuster therapy for millions of patients with resistant hypertension. But, what exactly happened that suddenly reversed this optimistic mood? Actually, it seems like there is no significant change; only the puzzle pieces are beginning to fall into place. Possibly because of the methodological problems involved in the initial studies, exaggerated interpretations led to heightened expectations from this exciting new treatment modality. There are three crucial points which need to be discussed.

Revealing the role of the autonomic nervous system in the development and maintenance of Goldblatt hypertension in rats

Despite extensive use of the renovascular/Goldblatt model of hypertension—2K-1C, and the use of renal denervation to treat drug resistant hypertensive patients, autonomic mechanisms that underpin the maintenance of this hypertension are important yet remain unclear. Our aim was to analyse cardiovascular autonomic function by power spectral density analysis of both arterial pressure and pulse interval measured continuously by radio telemetry for 6 weeks after renal artery clipping. Mean arterial pressure increased from 106 ± 5 to 185 ± 2 mm Hg during 5 weeks post clipping when it stabilized. A tachycardia developed during the 4th week, which plateaued between weeks 5 and 6. The gain of the cardiac vagal baroreflex decreased immediately after clipping and continued to do so until the 5th week when it plateaued (from − 2.4 ± 0.09 to − 0.8 ± 0.04 bpm/mm Hg; P < 0.05). A similar time course of changes in the high frequency power spectral density of the pulse interval was observed (decrease from 13.4 ± 0.6 to 8.3 ± 0.01 ms2; P < 0.05). There was an increase in both the very low frequency and low frequency components of systolic blood pressure that occurred 3 and 4 weeks after clipping, respectively. Thus, we show for the first time the temporal profile of autonomic mechanisms underpinning the initiation, development and maintenance of renovascular hypertension including: an immediate depression of cardiac baroreflex gain followed by a delayed cardiac sympathetic predominance; elevated sympathetic vasomotor drive occurring after the initiation of the hypertension but coinciding during its mid-development and maintenance.

Editorial paper Renal denervation – where do we stand in 2014?

Recently, resistant hypertension has received a significant amount of attention, due to its high prevalence among treated hypertensive patients as well as controversies regarding appropriate diagnostics and the development of successful treatment methods. Current results suggest that patients with resistant hypertension are at a higher risk of cardiovascular events and end-organ damage compared to patients with adequately controlled hypertension. Therefore, the introduction of novel, effective treatment methods that would overcome treatment resistance to achieve target blood pressure and reduce the overall cardiovascular risk remains nowadays one of the most important issues in hypertension management. Undoubtedly, the introduction of renal denervation in 2009 was a significant advance. Three-year follow-up data from the Simplicity HTN-1 registry and randomized Simplicity HTN-2 trial confirmed the efficacy and safety of renal denervation in the treatment of resistant hypertension. These promising results led to the introduction of the Simplicity HTN-3 trial in the United States, which so far has enrolled over 500 patients. For the first time patients have also been randomized to a ‘sham’ group. Many other studies have shown beneficial effects of this method in the reduction of end-organ complications and on the course of co-morbidities such as obstructive sleep apnoea, cardiac arrhythmias, heart failure and metabolic disorders. Additionally, a Global Simplicity Registry involving 100 centres worldwide has been established with the aim to enrol and follow up 5000 patients undergoing renal denervation. In Poland 11 centres have been eligible to introduce this method under the National Denervation Registry scheme, which is coordinated by the Institute of Cardiology in Warsaw. Research development and the increasing experience with renal denervation has been endorsed by the European Society of Hypertension and the European Society of Cardiology as shown by expert consensus statements issued in 2012 and 2013 that delineate the treatment indications of this method. A significant milestone since the introduction of renal denervation in the treatment of resistant hypertension was a short announcement recently published by Medtronic Inc. in mid- January regarding the Simplicity HTN-3 trial. The company mentioned that the study did not meet its major end-point, which was a reduction of systolic blood pressure after 6 months. Nonetheless, the company stressed that the secondary end-point has been met, namely patient safety. This short and incomprehensive announcement has caused international turmoil regarding the use of renal denervation in the treatment of resistant hypertension. However, during the Resistant Hypertension Course in Berlin, Germany (20–22 February 2014) leading experts in the field of interventional treatment of hypertension stated that studies so far have provided data proving the efficacy of renal denervation. So far, comprehensive data from the Simplicity HTN-3 trial remain unknown and further discussion on the role of renal denervation in the treatment of resistant hypertension based on this trial and other completed and ongoing studies will be possible when the results are published at the end of March 2014.

Renal sympatisk denervering ved terapiresistent hypertensjon

Renal denervation (RDN) has been introduced as a potential new treatment for patients with treatment-resistant hypertension, defined as a blood pressure above 140/90 mm Hg despite treatment with at least three antihypertensive drugs. We present an overview of this type of treatment, describe the method and discuss its possible future uses. The review is based on a discretionary selection of relevant articles from our archive, our own experience and a literature search in PubMed. The use of RDN for treatment-resistant hypertension is based on a single randomised study with a total of 104 patients, in which the intervention group experienced a fall in blood pressure of 32/12 mm Hg, while blood pressure in the control group remained unchanged. More than 16,000 patients, particularly in Germany, have been treated on this basis. In the USA, data from a larger randomised study (n = 530) that includes sham surgery are awaited before any decision is made on whether to approve the method for use. Before RDN can become recommended treatment in Norway, more evidence is required that the method lowers blood pressure, and that this reduces morbidity and mortality.

The role of renal denervation for the treatment of resistant hypertension

Hypertension affects more than one-fourth of the adult population worldwide and is a major risk factor for cardiovascular and kidney disease. Currently, the majority of patients with hypertension do not reach goal blood pressure (BP) targets, and cardiovascular risk is increased further for patients with treatment-resistant hypertension, defined as office BP above goal despite pharmacological treatment with three or more antihypertensive medications at optimal doses including a diuretic. Although missed diagnosis of secondary forms of hypertension, physician inertia and non-adherence with prescribed medication are important contributors to the phenomenon of resistant hypertension that need to be addressed, there is a need for alternative therapeutic approaches. Renal sympathetic denervation is a minimally invasive endovascular procedure that disrupts renal efferent and afferent neural connections, both of which are important regulators of BP control. Limited data from recent clinical trials indicate that this approach is safe and effectively lowers BP in patients with treatment-resistant hypertension. Accumulating data is emerging to suggest that renal sympathetic denervation may also have utility beyond treatment-resistant hypertension. This review aims to briefly summarize the existing evidence for the use of renal denervation (RDN) in patients with treatment-resistant hypertension and to explore the potential utility of RDN in other pathological states associated with sympathetic dysfunction.

Chronic kidney disease: role of sympathetic nervous system activation and potential benefits of renal denervation

The prevalence of chronic kidney disease (CKD) and end-stage renal disease continues to increase worldwide. Hypertension and diabetes are recognised as two major factors contributing to further progression of CKD. Importantly, progressive renal impairment increases cardiovascular morbidity and mortality. Despite advances in pharmacological antihypertensive and anti-diabetic approaches, the alarming number of patients developing nephropathy indicates the failure of the available treatment strategies. The relevance of sympathetic activation for the development and progression of chronic kidney disease is well established. Likewise, progressive renal failure results in exaggerated sympathetic activation leading to a vicious cycle, providing the rationale for the use of renal denervation to modulate directly the mechanisms underlying disease progression. While initial data on the safety and effectiveness of the procedure to lower BP were obtained in patients with resistant hypertension and preserved renal function, there are now preliminary data to suggest that this approach can also be applied safely in patients with stage 3-4 CKD. Similarly, first reports applying renal denervation in patients with end-stage renal disease on dialysis demonstrate favourable effects. If appropriately designed clinical trials can confirm these initial observations, renal denervation may become a valuable new treatment option for the large cohort of patients with CKD.

Afferent renal nerve stimulation excites RVLM projecting PVN neurons in rats

Recently renal denervation in hypertensive patients has proven to be very successful, however the underlying mechanism is not entirely clear. To determine if pre‐autonomic neurons in the paraventricular nucleus of the hypothalamus (PVN) are responsive to afferent renal nerve stimulation (ARN‐Sti), extracellular recording was used to investigate the contribution of the rostral ventrolateral medulla (RVLM) projecting PVN (PVN‐RVLM) neurons to ARN‐Sti. We also examined if these same neurons were responsive to baroreflex (BR) (i.v. injection of phenylephrine), or cardiac sympathetic afferent reflex (CSAR) (epicardial bradykinin). In 109 spontaneously active neurons recorded in the PVN of anesthetized rats, 25 units were antidromically activated from the RVLM. Among units classified as RVLM projecting PVN neurons, 84% (21/25) were activated by ARN‐Sti and the baseline discharge rate was significantly higher in them compared to those that were not activated by ARN‐Sti (16%, 4/25). In addition, almost all of neurons sensitive to ARN‐Sti were sensitive to BR (95%) and CSAR (100%). Among the non‐evoked neurons (not responding to stimulated from the RVLM) in the PVN, 23% respond to ARN‐Sti while 77% did not; most of the ARN sensitive neurons (83%) were responsive to baroreflex stimulation. Non of the non‐evoked neurons respond to CSAR. These results demonstrate that sensory information originating in kidney is integrated at the level pre‐autonomic neurons within the PVN, providing a novel mechanistic insight for use of renal denervation in modulation of sympathetic outflow in disease states such as hypertension and heart failure. Supported by NIH 62222.

Non-pharmacological methods in the treatment of resistant hypertension

Arterial hypertension is the most common chronic cardiovascular disease affecting about 25% of the adult population. Meta-analyses have demonstrated a linear relationship between blood pressure and the risk of cardiovascular events. Resistant hypertension defined as failure to reach blood pressure targets despite treatment with three antihypertensive drugs including a diuretic represents a serious clinical problem. It has been estimated that it affects between 8.9% and 12.8% of all treated hypertensive subjects. In resistant hypertension the optimal blood pressure is illusive despite very well tailored therapy. Management of resistant hypertension is exactly the field where blood pressure-controlling non-pharmacological methods fit best. The present article aims at throwing light on these methods' principles of action, on who the target patient groups are and the respective results. Two methods are especially reviewed here: the carotid baroreflex stimulation and the transcatheter renal sympathetic denervation. Current results from the use of renal denervation suggest stable efficiency of the method, the results becoming significant 6 months after the procedure is applied and sustained for two years in the follow-up. As much as 90% of the treated patients respond to the procedure. The transcatheter renal denervation is associated with only 2.61% of procedural complications. The baroreflex carotid stimulation, too, is known to produce a stable effect on blood pressure: the effect become obvious at 12 months in 88% of the treated subjects. The neurologic complications associated with the procedure are reported to occur in 4.4% of cases. The present review article clearly demonstrates that non-pharmacological methods for treatment of resistant hypertension show great promise despite some open questions concerning their long term effects and procedural safety.