Catheter-based Renal Sympathetic Denervation Research Articles

SPONTANEOUS, INDEPENDENT, SINGLE-CENTER RDN REGISTRY OF A RESISTANT HYPERTENSION MULTIDISCIPLINARY TEAM

Objective: Uncontrolled resistant hypertension (URH) is defined as Systolic Blood Pressure above 140mmHg despite at least 3 maximally tolerated doses of antihypertensive drugs including a diuretic. Renal sympathetic denervation (RDN) has proved efficacy in the sponsored SPYRAL and RADIANCE studies. However, little evidence is available from independent studies. Furthermore, patients with glomerular filtrate rate <45ml/min have been systematically excluded. This study aims to evaluate the safety and the efficacy of catheter-based radiofrequency RDN in patients with URH, including those with renal impairment. Design and method: Consecutive unselected patients with URH undergoing RDN were enrolled, assessed in a multidisciplinary team involving cardiologist, nephrologist and hypertension specialists, that excluded secondary forms. Efficacy was defined as change of office (OBP) and ambulatory blood pressure monitoring (ABPM) after RDN, safety as the absence of device-related major complication (BARC classification), end-stage renal disease, stroke, acute myocardial infarction and any cause of death within 1 month. 107 patients underwent RDN from 2012 to December 2023. The population had multiple comorbidities: 45% were smokers, 43% diabetic, 35% had peripheral artery disease, 30% coronary artery disease, 57% CKD. The average number of antihypertensive medications was 4.83±1.2 Baseline ABPM and OBP were 151.18±20,97/87,88±14,39mmHg and 155,92±24/85,25±15,5 mmHg, respectively Results: . At 12-month a significant reduction of systolic OBP and ABPM, respectively by -17.51±3.70 mmHg (P=0.001) and -7.03±3.37 mmHg (P=0.04) was noticed. BP reduction at 12-month follow-up was observed also among eGFR <45 ml/min, with a reduction by -18.73±7.14mmHg (P=0.02) in systolic OBP and by -17.81±7.49 (P=0.03) in ABPM. The therapeutic burden was slightly reduced baseline to 4 (3-5) at follow-up (p<0.01). No major complications were observed and renal function was stable up to 12 months, compared to baseline (1.87±2.37 vs. 2.44±3.56; -0.57±0.32; p=0.08). Conclusions: RDN on top of medical therapy is safe and feasible in patients with URH, even in a high-risk CKD population with multiple comorbidities. A significant reduction of SBP also in this subgroup up to 12 months was reported without undesired effects. Furthermore, our experience underlines the central role of multidisciplinary team evaluation for the appropriate management of URH.

Catheter-Based Ultrasound Renal Denervation in Patients with Resistant Hypertension: A Systematic Review

Background: The maintenance and development of hypertension are fundamentally dependent on renal sympathetic hyperactivity. Through regulation of the renal sympathetic nerves, catheter-based renal sympathetic denervation has been demonstrated to dramatically lower blood pressure (BP) in patients with resistant hypertension (systolic blood pressure 160 mm Hg on three or more antihypertensive medicines, including a diuretic). This study assessed a catheter-based ultrasound device of the next generation intended to maximize nerve coverage using circumferential ultrasound energy. This study's objective is to describe the results of renal denervation (RDN) in patients with resistant hypertension using a catheter-based ultrasonography device to measure blood pressure and safety. A potential new non-pharmacological therapy for resistant hypertension is renal denervation. Method: PubMed, Web of Science, Science Direct, Cochrane Library, and Google Scholar were thoroughly searched for relevant material. Throughout this meticulous process, the Rayyan QRCI was used. Results: our review included 10 studies with parameters including the period of study, age range of patients, office blood pressure, ambulatory blood pressure and the used approach. Clinical studies are required to determine whether this method is effective in treating this resistant hypertension. Conclusion: In individuals with resistant hypertension, catheter-based ultrasound renal denervation significantly and persistently lowers blood pressure and has no negative effects on renal function or renal artery anatomy.

First Nerve-Related Immunoprobe for Guidance of Renal Denervation through Colocalization of NIR-II and Photoacoustic Bioimaging.

Nerve-related fluorophores generally locate in the visible or near-infrared region with shallow penetration depth and easy uptake by surrounding tissues. Prolonging the optical window promotes resolution by minimizing photoscattering and eliminating autofluorescence for NIR-II (second near infrared; 1000-1700nm) and photoacoustic bioimaging. In addition, combination of the two could help in colocalization of targets at the 3D level. Catheter-based renal sympathetic denervation (RDN), an alternative treatment recently finishing its clinical evaluation for treating resistant hypertension, is highly dependent on experience and in urgent demand for in vivo guidance in locating the nerve over the renal artery. Here, an NIR-II and photoacoustic bioimaging system based on a dye-modified anti-tyrosine-hydroxylase antibody (TH-ICGM) to illustrate the peritoneal sympathetic nerve-related region are combined. With high resolution (0.15mm) in NIR-II region for both absorbance (λex = 925nm) and fluorescence (bioimaging in λem ≥ 1300nm), TH-ICGM succeeds in providing 3D coordinates of procedure position with a precision in 0.1mm. As the first nerve-related NIR-II immunoprobe, TH-ICGM has great clinical potential as assistance for nerve-related interventions.

Catheter-based renal sympathetic nerve denervation on hypertension management outcomes.

BACKGROUNDRenal sympathetic denervation (RSD) provides a minimally invasive interventional treatment modality for patients with resistant hypertension. However, the post-operative outcomes remain a key area of investigation since its earliest clinical trials. AIMTo evaluate patient outcomes after RSD intervention among peer-reviewed patient cases.METHODSA systematic review of literature on MEDLINE, Google Scholar, and the Cochrane Database of Systematic Reviews for RSD case studies to assess post-operative hypertension readings and medical management.RESULTSAmong 51 RSD cases, the post-operative RSD patients report an apparent reduction with a mean number of 3.1 antihypertensive medications. The mean systolic arterial blood pressure 1 year following RSD was 136.0 mmHg (95%CI: 118.7-153.3).CONCLUSIONThe apparent improvements in office systolic blood pressure after 12 month post-operative RSD can support the therapeutic potential of this intervention for blood pressure reduction. Additional studies which utilized a uniform methodology for blood pressure measurement can further support the findings of this systematic review.

435 Renal denervation in a patient with uncontrolled arterial hypertension secondary to polycystic kidney disease

Abstract Aims Autosomal dominant polycystic kidney disease (ADPKD) represents the most common inherited cause of chronic kidney disease. Typical manifestations of this condition include secondary hypertension, abdominal pain, haematuria and urinary tract infections. Despite the progressive increase in the use of antihypertensive therapy in patients with ADPKD in the last decades, reaching blood pressure target is often difficult in this setting due to the complex physiopathology of arterial hypertension in ADPKD. Catheter-based renal sympathetic denervation (RDN) represents nowadays a therapeutic strategy to approach resistant hypertension. Based on consistent results of several sham-controlled clinical trials, the evidence of safety and efficacy of this procedure is increasing, also in patients with multiple comorbidities including chronic kidney disease. Patients with ADPKD often develop chronic severe kidney-related pain, caused by distension of the renal capsule due to the expansion of the cysts. RDN was proposed to be an effective therapeutic option able to relieve loin pain. Methods A 49-year-old man affected by ADPKD was referred to our centre for resistant uncontrolled arterial hypertension, despite combined therapy with five antihypertensive drugs. He also complained about intense loin pain and 3 years earlier underwent two surgical interventions to remove voluminous renal cysts, that did not relieve chronic pain. His kidney function was moderately decreased at presentation, with progressive decline in the previous years. After a multi-disciplinary discussion with a nephrologist and algologist, the patient was proposed for RDN with the aim of lowering blood pressure and reducing pain. He was treated in July 2018, and after the procedure, was observed a better control of blood pressure but no benefits on pain. Because of the persistence of intractable loin pain, the patient was submitted to a second RDN in December 2018. Also, after this procedure, blood pressure declined remarkably, decreasing his need for antihypertensive medications without a significant worsening of kidney function. Unfortunately, no benefit on chronic pain was observed. Results ADPKD is characterized by the progressive bilateral development of focal renal cysts. Cardiovascular complications, mainly related to hypertension, are a major cause of morbidity and mortality for these patients. RDN could be a valid and safe therapeutic option for the treatment of secondary hypertension in this setting.

120 Safety and efficacy of renal artery denervation for uncontrolled-resistant hypertension in a high risk population with CKD: the Verona real-world experience

Abstract Aims To evaluate the safety and the efficacy of catheter-based radiofrequency renal sympathetic denervation (RSD) in a daily practice population of patients with uncontrolled resistant hypertension on top of medical therapy. Methods and results Consecutive unselected patients with uncontrolled resistant hypertension undergoing RSD were enrolled. Office and ambulatory blood pressure (BP) monitoring were collected at baseline and 3, 6, and 12 months after RSD. Efficacy was assessed also in patients with an estimated glomerular filtration rate below 45 ml/min/1.73 m2. Patients were defined responders to RSD if systolic BP decreased by at least 5 mmHg at ambulatory BP or by 10 mmHg at office BP at the last follow-up available. Fifty-four patients with multiple comorbidities underwent RSD for uncontrolled-resistant hypertension from 2012 to 2021. Baseline office and ambulatory BP was 161.0/87.2 ± 24.1/15.6 mmHg and 155.4/87.5 ± 19.3/14.6 mmHg, respectively. At 12-month follow-up a significant reduction of office and ambulatory systolic BP, respectively by − 15.66 ± 29.73 mmHg (P < 0.01) and by − 11.3 ± 23.1 mmHg (P < 0.05), was noticed. BP reduction at 12-month follow-up among patients with eGFR <45 ml/min was similar to that obtained in patients with higher eGFR. Among patients treated before July 2020 with available follow-up (45/54) 36 patients (80%) were classified as responders. Combined hypertension, higher ambulatory systolic BP and lower E/E’ at baseline emerged as predictors of success of RSD at univariate analysis. Among responders and non-responders, the average medication number showed no significant difference at baseline and during follow-up. No major complications were observed and renal function was stable up to 12 months, even in patients with lowest eGFR at baseline. Conclusions RSD is safe and feasible in patients with uncontrolled resistant hypertension on top of medical therapy, even in a high-risk CKD population with multiple comorbidities, with a significant reduction of systolic BP and a trend of reduction of the diastolic BP up to 12 months. 775 Figure

Intravascular Ultrasound Can Be Used to Locate Nerves, but not Confirm Ablation, During Renal Sympathetic Denervation.

BackgroundNo methods exist for confirming nerve ablation in catheter-based renal sympathetic denervation (RDN).MethodsWe investigated the feasibility of using intravascular ultrasound (IVUS) to locate nerves and observe nerve integrity changes during RDN in a pig. To confirm our observations, we used post-RDN histological sections matched anatomically to the IVUS images.ResultsIVUS revealed multiple hypoechoic structures along the renal artery, whose locations matched those of nerves in the histological sections. Nerves clustered near the junction between the renal artery and vein. Histology confirmed necrosis of nerve bundles at RDN ablation sites, but no changes in echogenicity were observed using IVUS.ConclusionsAlthough IVUS cannot currently be used to confirm ablation during RDN, it clearly reveals some clusters of renal sympathetic nerves. It remains to be demonstrated how IVUS can guide RDN devices and potentially improve ablation success.

Renal Denervation for Hypertension: A Systematic Review and Meta-Analysis of Randomized,Blinded, Placebo-Controlled Trials.

The authors performed an updated meta-analysis of randomized placebo-controlled trials of renal denervation and specifically compared the effect of renal denervation in patients taking medications and in those not taking medications. Renal denervation has now undergone several blinded placebo-controlled trials, covering the spectrum from patients with drug-resistant hypertension to those not yet taking antihypertensive medications. All blinded placebo-controlled randomized trials of catheter-based renal sympathetic denervation for hypertension were systematically identified, and a random-effects meta-analysis was performed. The primary efficacy outcome was the change in ambulatory systolic blood pressure beyond the effect of the placebo procedure. Analysis was stratified by whether there was background antihypertensive medication use. There were 7 eligible trials, totaling 1,368 patients. Denervation significantly reduced ambulatory systolic (mean difference-3.61mmHg; 95% CI:-4.89 to -2.33mmHg; P< 0.0001), ambulatory diastolic (-1.85mmHg; 95%CI:-2.78 to-0.92mmHg; P< 0.0001), office systolic (-5.86mmHg; 95%CI:-7.77 to-3.94mmHg; P< 0.0001), and office diastolic (-3.63mmHg; 95%CI:-4.77 to-2.50; P< 0.0001) blood pressure. There was no evidence that the use of concomitant antihypertensive medication had a significant impact on the effect of denervation on any of these endpoints (Pinteraction=NS for each comparison). The randomized placebo-controlled trials show consistently that renal denervation provides significant reduction in ambulatory and office blood pressure. Although the magnitude of benefit, about 4/2mmHg, is modest, it is similar between patients on background antihypertensive medications and those who are not. Denervation could therefore be a useful strategy at various points for patients who are not willing to add antihypertensive agents. Whether the effect changes with time is currently unknown.

Catheter-Based Radiofrequency Renal Sympathetic Denervation Decreases Left Ventricular Hypertrophy in Hypertensive Dogs.

This study explored the effects of renal sympathetic denervation (RDN) on hyperlipidity-induced cardiac hypertrophy in beagle dogs. Sixty beagles were randomly assigned to the control group, RDN group, or sham-operated group. The control group was fed with a basal diet, while the other two groups were given a high-fat diet to induce model hypertension. The RDN group underwent an RDN procedure, and the sham-operated group underwent only renal arteriography. At 1, 3, and 6 months after the RDN procedure, the diastolic blood pressure (DBP) and systolic blood pressure (SBP) levels were markedly decreased in the RDN group relative to the sham group (P < 0.05). After 6 months, serum norepinephrine (NE) and angiotensin II (AngII), as well as left ventricular levels, in the RDN group were statistically lower than those in the sham group (P < 0.05). Also, the left ventricular mass (LVM) and left ventricular mass index (LVMI) were significantly decreased, while the E/A peak ratio was drastically elevated (P < 0.05). Pathological examination showed that the degree of left ventricular hypertrophy and fibrosis in the RDN group was statistically decreased relative to those of the sham group and that the collagen volume fraction (CVF) and perivascular circumferential collagen area (PVCA) were also significantly reduced (P < 0.05). Renal sympathetic denervation not only effectively reduced blood pressure levels in hypertensive dogs but also reduced left ventricular hypertrophy and myocardial fibrosis and improved left ventricular diastolic function. The underlying mechanisms may involve a reduction of NE and AngII levels in the circulation and myocardial tissues, which would lead to the delayed occurrence of left ventricular remodeling.

Obstructive Sleep Apnea-Induced Neurogenic Nocturnal Hypertension: A Potential Role of Renal Denervation?

There is a bidirectional, causal relationship between obstructive sleep apnea (OSA) and hypertension. OSA-related hypertension is characterized by high rates of masked hypertension, elevated nighttime blood pressure, a nondipper pattern of nocturnal hypertension, and abnormal blood pressure variability. Hypoxia/hypercapnia-related sympathetic activation is a key pathophysiological mechanism linking the 2 conditions. Intermittent hypoxia also stimulates the renin-angiotensin-aldosterone system to promote hypertension development. The negative and additive cardiovascular effects of OSA and hypertension highlight the importance of effectively managing these conditions, especially when they coexist in the same patient. Continuous positive airway pressure is the gold standard therapy for OSA but its effects on blood pressure are relatively modest. Furthermore, this treatment did not reduce the cardiovascular event rate in nonsleepy patients with OSA in randomized controlled trials. Antihypertensive agents targeting sympathetic pathways or the renin-angiotensin-aldosterone system have theoretical potential in comorbid hypertension and OSA, but current evidence is limited and combination strategies are often required in drug resistant or refractory patients. The key role of sympathetic nervous system activation in the development of hypertension in OSA suggests potential for catheter-based renal sympathetic denervation. Although long-term, randomized controlled trials are needed, available data indicate sustained and relevant reductions in blood pressure in patients with hypertension and OSA after renal denervation, with the potential to also improve respiratory parameters. The combination of lifestyle interventions, optimal pharmacological therapy, continuous positive airway pressure therapy, and perhaps also renal denervation might improve cardiovascular risk in patients with OSA.

Insights on safety and efficacy of renal artery denervation for uncontrolled-resistant hypertension in a high risk population with chronic kidney disease: first Italian real-world experience

AimsTo evaluate the safety and efficacy of catheter-based radiofrequency renal sympathetic denervation (RSD) in a daily practice population of patients with uncontrolled resistant hypertension, on top of medical therapy.MethodsConsecutive unselected patients with uncontrolled resistant hypertension undergoing RSD were enrolled. Office and ambulatory blood pressure (BP) measurements were collected at baseline and 3, 6 and 12 months after RSD. Efficacy was assessed even in patients with an estimated glomerular filtration rate (eGFR) below 45 mL/min/1.73 m2. Patients were defined as responders if systolic BP decreased by at least 5 mmHg at ambulatory BP or by 10 mmHg at office BP at their last follow-up visit.ResultsForty patients with multiple comorbidities underwent RSD from 2012 to 2019. Baseline office and ambulatory BP was 159.0/84.9 ± 26.2/14.9 mmHg and 155.2/86.5 ± 20.9/14.0 mmHg, respectively. At 12-month follow up a significant reduction in office and ambulatory systolic BP, respectively by − 19.7 ± 27.1 mmHg and by − 13.9 ± 23.6 mmHg, was observed. BP reduction at 12-month follow-up among patients with eGFR < 45 mL/min was similar to that obtained in patients with higher eGFR. Twenty-nine patients (74.4%) were responders. Combined hypertension, higher ambulatory systolic BP and lower E/E’ at baseline emerged as predictors of successful RSD at univariate analysis. No major complications were observed and renal function (was stable up to 12 months), even in patients with the lowest eGFR values at baseline.ConclusionRSD is safe and feasible in patients with uncontrolled resistant hypertension on top of medical therapy, even in a high-risk CKD population with multiple comorbidities, with a significant reduction in systolic BP and a trend towards a reduction in diastolic BP lasting up to 12 months.Graphic abstract

Effects of renal denervation on 24-h heart rate and heart rate variability in resistant hypertension.

Catheter-based renal sympathetic denervation (RDN) can reduce sympathetic activity and blood pressure (BP) in patients with hypertension. The present study aimed at investigating the effects of RDN on heart rate (HR), number of premature captions, and heart rate variability (HRV). A total of 105 patients (67% male, age 63.5 ± 10years) with resistant hypertension (BP 169 ± 22/89 ± 14mmHg) underwent bilateral RDN using a radiofrequency catheter (Symplicity Flex, Medtronic). 24-h Holter monitoring was performed at baseline and after 6months. Besides HR profile, the number of premature atrial (PAC) and ventricular captions (PVC), time and frequency domain-based HRV were analyzed. Data are presented as mean ± standard deviation or median (interquartile range). Office systolic and diastolic BP were reduced after RDN by 21.8 ± 25.2mmHg and 8 ± 18.7mmHg (p < 0.001 for both), respectively. Twenty-eight (27%) patients had a reduction of < 10mmHg in systolic BP. At baseline, mean 24-h HR was 65.7 ± 9.9bpm. The prevalence of PAC [median 1.2 (0.3-6.2)] and PVC [median 1.2 (0.1-13.9)] was low and values of HRV were within normal limits and not different between responders and non-responders. After 6months, patients with a baseline HR > 72min had a significant reduction in HR by 2.3 ± 7.1bpm. Parameters of HRV did not significantly change during follow-up. In patients with ≥ 6 PAC per hour at baseline, a significant median reduction of -12.4 (-37.4 to -2.3) PAC after 6months was documented (p = 0.002), which occurred independently from BP effects. The number of PVC was not significantly altered after RDN. In patients with resistant hypertension and elevated HR or high burden of PACs, RDN was associated with a reduction of HR and number of PAC. Parameters of HRV were not changed after RDN nor were predictive of response to RDN.

Selection of Patients with Resistant Arterial Hypertension for the Catheter-Based Renal Sympathetic Denervation

elaboration of algorithm for selection of patients with resistant arterial hypertension (AH) for Catheter-Based RenalSympathetic Denervation (CBRSD). We examined 284 patients with resistant AH. On stage 1 we excluded mostfrequent causes of secondary AH. In 247 patients (86.9 %) we established secondary character of AH, in 37 patients (13.1 %) AH wasfound to be essential. On stage 2 patients with essential AH were given 3-5 component hypotensive therapy. At the background of thistherapy we conducted 24‑hour ambulatory blood pressure monitoring (ABPM). CBRSD procedure was considered indicated if accordingto ABPM average 24‑hour blood pressure (BP) was above 150 and 100 mm Hg, and 24‑hour elevated BP load exceeded 60 %.In 13 of 37 patients (35 %) BP level satisfied these conditions. For CBRSD we used high frequency generator. Ablation was performedusing the Symplicity Catheter. Results were assessed in 1, 2, 9, 12, and 28 months. Target BP level at the background of minimaldoses of hypotensive drugs was achieved in 11 patients (85 %), what was confirmed by ABPM data. Levels of mean 24-4 hour systolicand diastolic BP significantly decreased from 173.9±14.9 to 143±21.3, р&lt;0.05, and from 108.2±8.7 to 91.4±13.8 mm Hg., р&lt;0.05,respectively. Index of elevated systolic BP time decreased from 78.2±14.6 to 49.8±29.6 %, р&lt;0.05. Best effect was achieved in patients with AH duration before the procedure less than 7 years. None of the patients had episodes of cerebral vascular insufficiency or heart failure progression. While determining indications to bilateral CBRSD one should be governed by such criteria as exclusion of symptomatic AH and objective proofs of AH resistance (according to ABPM at the background of hypotensive therapy).

Sham-Controlled Randomized Trials of Catheter-Based Renal Denervation in Patients With Hypertension

BackgroundThere are conflicting data regarding the relative effectiveness of renal sympathetic denervation (RSD) in patients with hypertension. ObjectivesThe purpose of this study was to evaluate the blood pressure (BP) response after RSD in sham-controlled randomized trials. MethodsDatabases were searched through June 30, 2018. Randomized trials (RCTs) with ≥50 patients comparing catheter-based RSD with a sham control were included. The authors calculated summary treatment estimates as weighted mean differences (WMD) with 95% confidence intervals (CIs) using random-effects meta-analysis. ResultsThe analysis included 977 patients from 6 trials. The reduction in 24-h ambulatory systolic blood pressure (ASBP) was significantly greater for patients treated with RSD than sham procedure (WMD −3.65 mm Hg, 95% CI: −5.33 to −1.98; p < 0.001). Compared with sham, RSD was also associated with a significant decrease in daytime ASBP (WMD −4.07 mm Hg, 95% CI: −6.46 to −1.68; p < 0.001), office systolic BP (WMD −5.53 mm Hg, 95% CI: −8.18 to −2.87; p < 0.001), 24-h ambulatory diastolic BP (WMD −1.71 mm Hg, 95% CI: −3.06 to −0.35; p = 0.01), daytime ambulatory diastolic BP (WMD −1.57 mm Hg, 95% CI: −2.73 to −0.42; p = 0.008), and office diastolic BP (WMD −3.37 mm Hg, 95% CI: −4.86 to −1.88; p < 0.001). Compared with first-generation trials, a significantly greater reduction in daytime ASBP was observed with RSD in second-generation trials (6.12 mm Hg vs. 2.14 mm Hg; p interaction = 0.04); however, this interaction was not significant for 24-h ASBP (4.85 mm Hg vs. 2.23 mm Hg; p interaction = 0.13). ConclusionsRSD significantly reduced blood pressure compared with sham control. Results of this meta-analysis should inform the design of larger, pivotal trials to evaluate the long-term efficacy and safety of RSD in patients with hypertension.

Anatomic Conformation of Renal Sympathetic Nerve Fibers in Living Human Tissues

Renal denervation using radiofrequency catheter ablation is known to eliminate the renal sympathetic nerve and to lower blood pressure in patients with resistant hypertension. We sought to investigate the detailed anatomic conformation of the peri-renal arterial sympathetic nerve fibers with living human specimens. Peri-renal arterial tissue was harvested from patients undergoing elective radical or simple nephrectomy. Digital images of each section from the distal arterial bifurcation to the proximal margin were obtained and analyzed after immunohistochemical staining with anti-tyrosine hydroxylase antibodies. A total of 3,075 nerve fibers were identified from 84 sections of peri-renal arterial tissue from 28 patients (mean age 62.5 ± 10.2 years, male 68%). Overall, 16% of nerve fibers were located at distances greater than 3 mm from the endoluminal surface of the renal artery. The median distance from the arterial lumen to the nerve fibers of the proximal, middle, and distal renal arterial segments was 1.51 mm, 1.48 mm, and 1.52 mm, respectively. The median diameter of the nerve fibers was 65 μm, and there was no significant difference between the segments. A substantial proportion of the sympathetic nerve fibers were located deeper in the peri-arterial soft tissue than in the lesion depth created by the conventional catheter-based renal sympathetic denervation system.

A4020 Reduction of Blood Pressure Immediately After Renal Artery Adventitia Stripping During Total Nephroureterectomy

Objectives: Two men on antihypertensive therapy underwent unilateral radical nephroureterectomy for cancer of the renal pelvis. Methods: When the renal artery adventitia was stripped and cauterized just before renal artery ligation, hemodynamic monitoring revealed a gradual decrease of blood pressure in both patients. Results: This was presumably due to removal of renal artery sympathetic nerves, similar to the mechanism of catheter-based renal sympathetic denervation, although anesthesia, fluid infusion, and/or mesenteric traction may have had an influence. Conclusion: A similar strategy involving thoracolumbar sympathectomy was reported about 50 years ago. The clinically significant blood pressure reduction in these patients suggests renal denervation is effective.

Predictors for profound blood pressure response in patients undergoing renal sympathetic denervation.

Renal sympathetic denervation (RDN) as treatment for hypertension shows highly variable results. Although some patients do not show any blood pressure (BP) change and in most patients a BP reduction of at least 5 mmHg can be found, some show a reduction at least 20 mmHg. We sought to identify predictors for such a profound BP response. Profound BP response was defined as drop of at least 20 mmHg in daytime systolic ambulatory BP measurement (ABPM) 3 months after catheter-based RDN. Three different denervation devices were used for RDN, and pulse wave velocity was determined invasively in a subgroup of patients. One hundred and ninety consecutive patients were included in this analysis. Profound BP response was found in 33 patients. Patients with profound BP response were younger (P = 0.04), presented with higher baseline ABPM values (P < 0.001), were treated with ultrasound-based RDN and received more often a combined treatment with two different diuretics (P = 0.005 for both). After 3 months, a treatment target of daytime BP less than 135 mmHg could be achieved more frequently in patients with profound BP response (61 vs. 17%, P < 0.001). Age, use of ultrasound RDN, combined diuretic therapy and baseline BP independently predicted pronounced BP reduction. A second multivariate logistic regression model including pulse wave velocity if available identified baseline BP, pulse wave velocity and use of ultrasound denervation as independent predictors for profound BP response. Younger vascular age, higher baseline BP, treatment with ultrasound RDN and combined diuretic therapy were found as predictors for a pronounced BP reduction following RDN, improving BP control at follow-up.

Role of the Sympathetic Nervous System and Its Modulation in Renal Hypertension.

The kidneys are densely innervated with renal efferent and afferent nerves to communicate with the central nervous system. Innervation of major structural components of the kidneys, such as blood vessels, tubules, the pelvis, and glomeruli, forms a bidirectional neural network to relay sensory and sympathetic signals to and from the brain. Renal efferent nerves regulate renal blood flow, glomerular filtration rate, tubular reabsorption of sodium and water, as well as release of renin and prostaglandins, all of which contribute to cardiovascular and renal regulation. Renal afferent nerves complete the feedback loop via central autonomic nuclei where the signals are integrated and modulate central sympathetic outflow; thus both types of nerves form integral parts of the self-regulated renorenal reflex loop. Renal sympathetic nerve activity (RSNA) is commonly increased in pathophysiological conditions such as hypertension and chronic- and end-stage renal disease. Increased RSNA raises blood pressure and can contribute to the deterioration of renal function. Attempts have been made to eliminate or interfere with this important link between the brain and the kidneys as a neuromodulatory treatment for these conditions. Catheter-based renal sympathetic denervation has been successfully applied in patients with resistant hypertension and was associated with significant falls in blood pressure and renal protection in most studies performed. The focus of this review is the neural contribution to the control of renal and cardiovascular hemodynamics and renal function in the setting of hypertension and chronic kidney disease, as well as the specific roles of renal efferent and afferent nerves in this scenario and their utility as a therapeutic target.

Catheter-based renal sympathetic denervation induces acute renal inflammation through activation of caspase-1 and NLRP3 inflammasome.

Objective:Catheter-based renal sympathetic denervation (RDN) is implemented as a strategy to treat resistant hypertension. Serum creatinine and estimated glomerular filtration rate have some limitations to predict the early stage of acute kidney injury (AKI). We investigated the changes of early inflammatory biomarkers in AKI following the RDN procedure.Methods:Twenty-five female swine were divided into three groups: normal control (Normal, n=5), sham-operated (Sham, n=5), and RDN groups (RDN, n=15). The RDN group was further subdivided into three subgroups according to the time of sacrifice: immediately (RDN-0, n=5), 1 week (RDN-1, n=5), and 2 weeks (RDN-2, n=5) after RDN. Renal cortical tissue was harvested, and clinical parameters and inflammatory biomarkers were checked.Results:There were no significant changes in the clinical parameters between the normal control and sham-operated groups using contrast media. Inflammatory interleukin (IL)-1β, IL-18, IL-6, tumor necrosis factor-α, and anti-inflammatory IL-10 increased immediately and then decreased at week 2 after RDN in the renal cortical tissue. Leaderless protein, IL-1α level, increased at week 1 and then decreased at week 2 after RDN. Caspase-1 increased immediately after RDN until week 2. Apoptosis-associated speck-like protein containing a caspase recruitment domain and NLRP3 expressions increased immediately and then decreased at week 2 after RDN.Conclusion:The RDN could induce acute renal inflammation through the activation of caspase-1 and NLRP3 inflammasome.

PP.15.20] COST-EFFECTIVENESS OF RENAL DENERVATION COMPARED TO ANTIHYPERTENSIVE DRUG THERAPY IN TRUE RESISTANT HYPERTENSION

Objective: Although the failure of the SYMPLICITY-3 trial in reaching its primary efficacy end-point, the catheter-based renal sympathetic denervation (RDN) remains the only tool to improve blood pressure (BP) control in patient with true resistant hypertension (RH). In the Veneto region, RDN is authorized only in two specialized centers, but in selected cases, is also performed in hospitals organized in the so-called Hub-model. Patients with RH are at a high risk for developing serious cardiovascular events increasing the global health costs. In this study, we assess cost-effectiveness and short-term clinical benefits of RDN.Design and method: A 48-years old male, with a history of hypertension dated for over 10 years was annually admitted to our department for high BP levels not controlled by therapy until 7 anti-hypertensive drugs. The search for a cause of secondary hypertension revealed no clues. He was diabetic, overweight, with stage-3 of chronic renal disease and had multiple organ damage. At the last admission, BP averaged 226/128 mmHg and his medications were: amlodipine 20 mg, Ramipril 10 mg, spironolactone 25 mg, furosemide 50 mg, doxasozine 8 mg daily. 24h-ambulatory BP measurement (Figure 1A) confirmed RH. Patient underwent to RDN procedure using a third generation SpyralTM catheter, a device that is associated with a reduced procedural time, contrast use and radiation exposure. RDN was performed without complications, and after 48 h BP lowered up to 50 mmHg with 3 antihypertensive drugs (Figure 1B). Medical records of the 10 years before the last hospitalization were collected, and on medical DRG the global costs for RH management has been calculated and compared with the cost of the RDN procedure. Results: RDN therapy resulted in an increase on health benefit both for BP control and pharmacological treatment, so that patient stopped taking 4 anti-hypertensive drugs. In 10 years of admissions, the global health costs of hypertension management reached more than 57.000 Euro compared to the about 6,000 Euro of the RDN procedure. Conclusions: RDN offers a meaningful and cost-effective alternative for achieving BP control, where traditional combination of antihypertensive pharmacologic strategies, have been proven to be ineffective.