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Renal nerves have critical roles in regulating blood pressure and fluid volume, and their dysfunction is closely related with cardiovascular diseases. Renal nerves are composed of sympathetic efferent and sensory afferent nerves. Activation of the efferent renal sympathetic nerves induces renin secretion, sodium absorption, and increased renal vascular resistance, which lead to increased blood pressure and fluid retention. Afferent renal sensory nerves, which are densely innervated in the renal pelvic wall, project to the hypothalamic paraventricular nucleus in the brain to modulate sympathetic outflow to the periphery, including the heart, kidneys, and arterioles. The effects of renal denervation on the cardiovascular system are mediated by both efferent denervation and afferent denervation. The first half of this review focuses on basic research using animal models of hypertension and heart failure, and addresses the therapeutic effects of renal denervation for hypertension and heart failure, including underlying mechanisms. The second half of this review focuses on clinical research related to catheter-based renal denervation in patients with hypertension. Randomized sham-controlled trials using second-generation devices, endovascular radiofrequency-based devices and ultrasound-based devices are reviewed and their results are assessed. This review summarizes the basic and clinical evidence of renal denervation to date, and discusses future prospects and potential developments in renal denervation therapy for cardiovascular diseases.

The aim of this study was to explore the long‐term clinical results of Renal denervation (RDN) from the adventitia of the renal artery plus unilateral laparoscopic adrenalectomy to treat patients with resistant hypertension caused by unilateral aldosterone‐producing adenoma (APA). Sixty patients with resistant hypertension caused by APA who were treated at Henan Provincial People's Hospital from December 2016 to March 2018 were selected and randomly assigned to undergo RDN from the adventitia of the renal artery plus adrenalectomy (RDN group, n = 30) or adrenalectomy alone (control group, n = 30). Office blood pressure (BP), antihypertensive medication usage and other laboratory characteristics were followed every 6 months through 36 months. Follow‐up data were available at 36 months for 23 of 30 subjects in the RDN group and for 21 of 30 subjects who were in the control group. At 36 months postprocedure, the reduction in the RDN group was 42.2 ± 21.6 mmHg and that in the control group was 29.8 ± 13.5 mmHg (p = .029 between the groups). During the follow‐up to 36 months postprocedure, no patients in either the RDN group or the control group died due to surgical complications, and the RDN group had no procedural complications, including renal artery dissection, perforation, and renal artery stenosis. There was no change in the mean eGFR of the two groups, and no serious adverse events were reported. In conclusion, RDN from the adventitia of the renal artery plus unilateral laparoscopic adrenalectomy resulted in sustained lowering of BP at 3 years in a selected population of subjects with resistant hypertension caused by unilateral APA without serious safety concerns.

Background Renal denervation (RDN) has emerged in recent years as a possible treatment for hypertension. The first sham-controlled trial showed a small magnitude and non-significant in the blood pressure (BP) lowering effect, also due to a substantial decrease of BP in sham arm. Considering this, we aimed to quantify the magnitude of BP decrease within the sham arm of Randomized Controlled Trials (RCT) with RDN in patients with hypertension. Methods Electronic databases were searched since inception until January 2022 for randomized sham-controlled trials which assessed the efficacy in lowering BP of the sham intervention for catheter-based RDN in adult patients with hypertension. The outcomes were change in ambulatory/office systolic and diastolic BP. Results A total of 9 RCT were included in the analysis enrolling a total of 674 patients. Sham intervention showed a decrease in all evaluated outcomes. Office systolic BP had a reduction of -5.52 mmHg [95%CI -7.91, -3.13] and office diastolic BP of -2.13 mmHg [95%CI -3.08, -1.17]. Sham procedure for RDN also showed a reduction of -3.41 mmHg [95%CI -5.08, -1.75] in ambulatory systolic BP and − 2.44 mmHg [95%CI -3.31, -1.57] in ambulatory diastolic BP. Conclusion Despite recent data indicating that RDN might be an effective treatment for patients with resistant hypertension when compared to a sham intervention, our results indicate that the sham intervention for RDN also has a significant effect on lowering Office and Ambulatory (24-h) Blood Pressure in adult patients with hypertension. This highlights that BP itself might be sensitive to placebo-like effect and also brings further difficulties in establishing the BP lowering efficacy of invasive interventions due to the magnitude of the sham effect.

Eight patients with office blood pressure >140/90 mmHg, despite being treated with at least three antihypertensive drugs, underwent catheter-based rel denervation. Secondary hypertension was excluded in all patients. Every patient underwent follow-up at 30 days, and then every 3 months. At 6 and 12 months the median value of systolic clinic blood pressure decreased from 161 mmHg (25th-75th percentiles: 158-191 mmHg) at baseline to 144 mmHg (25th-75th percentiles: 136-153 mmHg) at follow up (P=0.012), and the median value of diastolic clinic blood pressure decreased from 102 mmHg (25th-75th percentiles: 94-122 mmHg) at baseline to 90 mmHg (25th-75th percentiles: 78-99 mmHg) at follow-up (P=0.012). The number of medications decreased from 5 (range, 2-8) at baseline to 3.3 (range, 0-6) at follow up. There was a significant decrease of left ventricular mass index from a median of 160 g/m2 (25th-75th percentiles: 147-151 g/m2) at baseline to 126 g/m2 (25th-75th percentiles 107-151 g/m2) at follow-up (P=0.043) was detected. The rel function, and metabolic and neurohumoral parameters, did not change significantly. No complications were observed.

Renal denervation is a promising new non-pharmacological treatment for resistant hypertension. However, there is a lack of data from Asian patients. The REQUIRE trial investigated the blood pressure-lowering efficacy of renal denervation in treated patients with resistant hypertension from Japan and South Korea. Adults with resistant hypertension (seated office blood pressure ≥150/90 mmHg and 24-hour ambulatory systolic blood pressure ≥140 mmHg) with suitable renal artery anatomy were randomized to ultrasound renal denervation or a sham procedure. The primary endpoint was change from baseline in 24-hour ambulatory systolic blood pressure at 3 months. A total of 143 patients were included (72 renal denervation, 71 sham control). Reduction from baseline in 24-hour ambulatory systolic blood pressure at 3 months was not significantly different between the renal denervation (-6.6 mmHg) and sham control (-6.5 mmHg) groups (difference: -0.1, 95% confidence interval -5.5, 5.3; p = 0.971). Reductions from baseline in home and office systolic blood pressure (differences: -1.8 mmHg [p = 0.488] and -2.0 mmHg [p = 0.511], respectively), and medication load, did not differ significantly between the two groups. The procedure-/device-related major adverse events was not seen. This study did not show a significant difference in ambulatory blood pressure reductions between renal denervation and a sham procedure in treated patients with resistant hypertension. Although blood pressure reduction after renal denervation was similar to other sham-controlled studies, the sham group in this study showed much greater reduction. This unexpected blood pressure reduction in the sham control group highlights study design issues that will be addressed in a new trial. CLINICAL TRIAL REGISTRATION: NCT02918305 ( http://www.clinicaltrials.gov ).

Background： Catheter-based renal denervation （RDN） is a novel treatment tbr resistant hypertension （RH）. A recent meta-analysis reported that RDN did not significantly reduce blood pressure （BP） based on the pooled effects with mild to severe heterogeneity. The aim of the present study was to identify and reduce clinical sources of heterogeneity and reassess the safety and efficacy of RDN within the identified homogeneous subpopulations. Methods： This was a meta-analysis of 9 randomized clinical trials （RCTs） among patients with RH up to June 2016. Sensitivity analyses and subgroup analyses were extensively conducted by baseline systolic blood pressure （SBP） level, antihypertensive medication change rates, and coronary heart disease （CHD）. Results： In all patients with RH, no statistical differences were found in mortality, severe cardiovascular events rate, and changes in 24-11 SBP and office SBP at 6 and 12 months. However, subgroup analyses showed significant differences between the RDN and control groups. In the subpopulations with baseline 24-h SBP 〉 155 mmHg （ 1 mmHg = 0.133 kPa） and the infrequently changed medication, the use of RDN resulted in a significant reduction in 24-h SBP level at 6 months （P = 0.100 and P = 0.009, respectively）. Subgrouping RCTs with a higher prevalent CHD in control showed that the control treatment was significantly better than RDN in office SBP reduction at 6 months （P 〈 0.001 ）. Conclusions： In all patients with RH, the catheter-based RDN is not more effective in lowering ambulatory or office BP than an optimized antihypertensive drug treatment at 6 and 12 months. However, among RH patients with higher baseline SBP, RDN might be more effective in reducing SBR

Elevated morning and nighttime blood pressures (BP) are associated with increased risk of cardiovascular events such as stroke and myocardial infarction. We compared the long-term changes in morning and nighttime BP in patients with uncontrolled hypertension (office systolic BP between 150 and <180 mmHg/diastolic BP ≥ 90 mmHg; mean ambulatory systolic BP (SBP) between 140 and <170 mmHg; 1–3 prescribed antihypertensive medications). Eighty patients were randomized to RDN or sham control. In patients taking at least 3 antihypertensive medications at 36 months ( N  = 23 RDN group; N  = 23 sham group), the 24 h ambulatory SBP as well as morning (7:00–9:00AM) and nighttime (1:00–6:00AM) ambulatory SBP were significantly lower for the RDN group compared to sham control (24 h SBP: −20.2 vs. −10.2, p  = 0.0087; morning SBP: −23.9 vs. −8.0 mmHg, p  = 0.029; nighttime SBP: −20.8 vs. −7.2 mmHg, p  = 0.0011). At 36 months, 24 h SBP was controlled to <130 mmHg in 40% of RDN patients in the morning compared to 6% for the sham group; P  = 0.021 and in 80% of the RDN patients at night compared to 39% in the sham group; P  = 0.019. Major adverse events through 36 months were rare in both groups, and there were no renal artery re-interventions or vascular complications. Morning and nighttime SBP were significantly lower in patients prescribed at least 3 antihypertensive medications at 36 months in the SPYRAL HTN-ON MED trial for RDN compared with sham control. The results suggest RDN has significant benefit when the risk of cardiovascular events is highest.

Cardiometabolic disorders are associated with a substantial loss in quality of life and pose a large burden on healthcare systems worldwide. Overactivation of the sympathetic nervous system has been shown to be a key player in several aspects relating to cardiometabolic disturbances. While diet- and exercise-induced approaches to help reduce weight remains the main strategy to combat metabolic disorders, this is often difficult to achieve. Current pharmacological approaches result in variable responses in different patient cohorts and long-term efficacy may be limited by medication side effects and non-adherence in the long term. There is a clear clinical need for complementary therapies to curb the burden of cardiometabolic disease. One such approach may include interventional sympathetic neuromodulation of organs relevant to cardiometabolic control. Data from sham-controlled clinical trials demonstrate the feasibility, safety and efficacy of catheter-based renal denervation. In analogy, denervation of the common hepatic artery is now feasible in humans and may prove to be similarly useful in modulating sympathetic overdrive directed towards the liver, pancreas and duodenum. Such a targeted multi-organ neuromodulation strategy may beneficially influence multiple aspects of the cardiometabolic disease continuum including blood pressure, glucose and lipid control.

Renal denervation (RDN) is a catheter-based interventional approach that targets renal sympathetic nerves to modulate sympathetic overactivity, a key pathophysiological driver of resistant hypertension and associated cardiovascular complications. In contrast to pharmacological approaches, the therapeutic effect of RDN does not rely on patient adherence. Originally indicated for severe resistant hypertension, RDN has since shown consistent antihypertensive efficacy across a broad range of hypertensive patients in recent sham-controlled studies. In this review, we discuss the pathophysiological foundation underlying RDN, consolidate the current clinical evidence supporting its therapeutic efficacy, describe the spectrum of available ablation technologies, and evaluate its expanding applications in conditions driven by sympathetic overactivity.

The efficacy of renal denervation has been controversial, but recent randomized sham-controlled trials demonstrated significant blood pressure reductions after renal denervation in patients with hypertension. We conducted a systematic review and updated meta-analysis to evaluate the effects of renal denervation on ambulatory and office blood pressures in patients with hypertension. Databases were searched up to 25 May 2021 to identify randomized, sham-controlled trials of renal denervation. The primary endpoint was change in 24 h ambulatory systolic blood pressure with renal denervation versus sham control. The secondary endpoints were daytime and nighttime systolic blood pressure, and office systolic blood pressure. A sub-analysis determined outcomes by medication, procedure, and device. From nine trials, 1555 patients with hypertension were randomized to undergo renal denervation (n = 885) or a sham procedure (n = 670). At 2-6 months after treatment, renal denervation significantly reduced 24 h ambulatory systolic blood pressure by 3.31 mmHg (95% confidence interval: -4.69, -1.94) compared with the sham procedure (p < 0.001). Renal denervation also reduced daytime SBP by 3.53 mmHg (-5.28, -1.78; p < 0.001), nighttime SBP by 3.20 mmHg (-5.46, -0.94; p = 0.006), and office SBP by 5.25 mmHg (-7.09, -3.40; p < 0.001) versus the sham control group. There were no significant differences in the magnitude of blood pressure reduction between first- and second-generation trials, between devices, or with or without medication. These data from randomized sham-controlled trials showed that renal denervation significantly reduced all blood pressure metrics in medicated or unmedicated patients with hypertension, including resistant/uncontrolled hypertension. Future trials should investigate the long-term efficacy and safety of renal denervation.