Renal sympathetic denervation in patients with treatment-resistant hypertension (The Symplicity HTN-2 Trial): a randomised controlled trial

Esler, Murray; Krum, Henry; Sobotka, Paul; Schlaich, Markus P.; Schmieder, Roland E.; Böhm, Michael; Mahfoud, Felix; Sievert, Horst; Wunderlich, Nina; Rump, Lars Christian; Vonend, Oliver; Uder, Michael; Lobo, Mel; Caulfield, Mark; Ērglis, Andrejs; Azizi, Michel; Sapoval, Marc; Thambar, S.; Persu, Alexandre; Renkin, Jean; Schunkert, Heribert; Weil, Joachim; Hoppe, Uta C.; Walton, Tony; Scheinert, Dierk; Binder, Thomas; Januszewicz, Andrzej; Witkowski, Adam; Ruilope, Luís M.; Whitbourn, Robert; Bruck, Heike; Downes, Mark; Lüscher, Thomas F.; Jardine, Alan G.; Webster, Mark; Zeller, Thomas; Sadowski, Jerzy; Bartuś, Krzysztof; Straley, Craig A.; Barman, Neil C.; Lee, David P.; Witteles, Ronald; Bhalla, Vivek; Massaro, Joseph M.

doi:10.1016/s0140-6736(10)62039-9

Cited by 1,935 publications

(465 citation statements)

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“…Early clinical trials of renal denervation showed significant blood pressure improvements (Esler et al 2010;Krum et al 2009). Interestingly, renal denervation was also associated with significant decreases in blood glucose levels (Mahfoud et al 2011;Witkowski et al 2011).…”

Section: Introductionmentioning

confidence: 99%

Electrical stimulation of renal nerves for modulating urine glucose excretion in rats

et al. 2018

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Background: The role of the kidney in glucose homeostasis has gained global interest. Kidneys are innervated by renal nerves, and renal denervation animal models have shown improved glucose regulation. We hypothesized that stimulation of renal nerves at kilohertz frequencies, which can block propagation of action potentials, would increase urine glucose excretion. Conversely, we hypothesized that low frequency stimulation, which has been shown to increase renal nerve activity, would decrease urine glucose excretion. Methods: We performed non-survival experiments on male rats under thiobutabarbital anesthesia. A cuff electrode was placed around the left renal artery, encircling the renal nerves. Ureters were cannulated bilaterally to obtain urine samples from each kidney independently for comparison. Renal nerves were stimulated at kilohertz frequencies (1-50 kHz) or low frequencies (2-5 Hz), with intravenous administration of a glucose bolus shortly into the 25-40-min stimulation period. Urine samples were collected at 5-10-min intervals, and colorimetric assays were used to quantify glucose excretion and concentration between stimulated and non-stimulated kidneys. A KruskalWallis test was performed across all stimulation frequencies (α = 0.05), followed by a post-hoc Wilcoxon rank sum test with Bonferroni correction (α = 0.005). Results: For kilohertz frequency trials, the stimulated kidney yielded a higher average total urine glucose excretion at 33 kHz (+ 24.5%; n = 9) than 1 kHz (− 5.9%; n = 6) and 50 kHz (+ 2.3%; n = 14). In low frequency stimulation trials, 5 Hz stimulation led to a lower average total urine glucose excretion (− 40.4%; n = 6) than 2 Hz (− 27.2%; n = 5). The average total urine glucose excretion between 33 kHz and 5 Hz was statistically significant (p < 0.005). Similar outcomes were observed for urine flow rate, which may suggest an associated response. No trends or statistical significance were observed for urine glucose concentrations. Conclusion: To our knowledge, this is the first study to investigate electrical stimulation of renal nerves to modulate urine glucose excretion. Our experimental results show that stimulation of renal nerves may modulate urine glucose excretion, however, this response may be associated with urine flow rate. Future work is needed to examine the underlying mechanisms and identify approaches for enhancing regulation of glucose excretion.

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Section: Introductionmentioning

confidence: 99%

Electrical stimulation of renal nerves for modulating urine glucose excretion in rats

et al. 2018

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“…The best-known is renal denervation. It initially proved effective in resistant hypertensive patients in the Symplicity HTN-2 trial [21], but the Symplicity HTN-3 trial had disappointing results [22]. It was found that renal denervation improves cardiac remodelling and function in post-myocardial infarction HF [23] and reduces atrial fibrillation recurrences in combination with pulmonary vein isolation in patients with resistant hypertension [24].…”

Section: Discussionmentioning

confidence: 99%

Effect of High Thoracic Sympathetic Nerve Block on Serum Collagen Biomarkers in Patients with Chronic Heart Failure

Sun

Liu²,

Qu³

2016

Cardiology

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Objectives: The impact of high thoracic sympathetic block (HTSB) on myocardial fibrosis in chronic heart failure (HF) is unclear. Myocardial collagen synthesis can be assessed by measuring circulating biomarkers. Weobserved the effect of HTSB on serum collagen biomarkers in HF. Methods: Forty-four patients were randomized to a control and a HTSB group. They received routine medications. Repeated epidural injections were given to the HTSB group for 4 weeks. Echocardiography and measurements of serum carboxy-terminal propeptide of procollagen type I (PICP) and amino-terminal propeptide of procollagen type III (PIIINP) were performed at baseline and 4 weeks later. Results: There were significant reductions in left atrial diameter, left ventricular (LV) diameter and volume, LV weight index (LVWI) and serum PICP and PIIINP levels in the HTSB group (p < 0.05). The changes in LV end-systolic volume and ejection fraction (LVEF) were greater in the HTSB group than in the control group (p < 0.05). In the HTSB group, the decreases in PICP and PIIINP were correlated with the decrease in LVWI (PICP: r = 0.695, p = 0.000; PIIINP: r = 0.642, p = 0.001), and the decrease in PICP was negatively associated with the rise in LVEF (r = -0.813, p = 0.000). Conclusion: HTSB reduces myocardial fibrosis in HF, which may accompany the improvement of LV hypertrophy anddysfunction.

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“…From the group of 106 enrolled patients, 52 were assigned to renal denervation and 54 were included in a control group. Six- and twelve-month follow-up showed that patients with renal denervation had significantly greater decrease in office arterial BP than controls [26,27]. Further evidence for the efficacy of renal denervation in the treatment of hypertension came from other small studies.…”

Section: Renal Denervation In Drug-resistant Hypertensionmentioning

confidence: 99%

Drug Resistant Hypertension - No SIMPLE Way Out

Skrzypecki

Ufnal

2015

Kidney Blood Press Res

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Hypertension poses growing challenge for health policy-makers and doctors worldwide. Recently published results of Symplicity-III trial (HTN-3), the first blinded, randomized, multicenter study on the efficacy of renal denervation for the treatment of resistant hypertension did not show a significant reduction of BP in patients with resistant hypertension 6 months after renal-artery denervation, as compared with controls. In this paper we review clinical and experimental studies on renal denervation. In order to identify causes of inconsistent results in renal denervation studies we look at basic science support for renal denervation and at designs of clinical trials.

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Renal sympathetic denervation in patients with treatment-resistant hypertension (The Symplicity HTN-2 Trial): a randomised controlled trial

Cited by 1,935 publications

References 25 publications

Electrical stimulation of renal nerves for modulating urine glucose excretion in rats

Electrical stimulation of renal nerves for modulating urine glucose excretion in rats

Effect of High Thoracic Sympathetic Nerve Block on Serum Collagen Biomarkers in Patients with Chronic Heart Failure

Drug Resistant Hypertension - No SIMPLE Way Out

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