Limited destruction of renal nerves after catheter-based renal denervation: results of a human case study

Vink, Eva E.; Goldschmeding, Roel; Vink, Aryan; Weggemans, Callista; Bleijs, Ronald L.A.W.; Blankestijn, Peter J.

doi:10.1093/ndt/gfu192

Cited by 80 publications

(54 citation statements)

References 6 publications

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“…15,22 In other words, a persistent increase in BP in response to RNS after RDN might already indicate that a patient is likely to be a nonresponder. As shown by Vink et al, 23 RDN does not always result in circular lesions completely destroying the renal nerve tissue. By applying RNS to these areas, the remaining functional nerve tissue might be detected and ablated afterward.…”

Section: Discussionmentioning

confidence: 84%

Persistent Increase in Blood Pressure After Renal Nerve Stimulation in Accessory Renal Arteries After Sympathetic Renal Denervation

et al. 2016

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Recently, we showed that BP increase elicited by high-frequency renal nerve stimulation (RNS) is significantly blunted after RDN. 15 This approach may allow to gain further insights into the differences in BP response to RDN in patient with or without renal accessory arteries. We hypothesized that after successful RDN, there will be no significant increase in BP after RNS in the main arteries, whereas there will still be an increase in BP in response to RNS in the accessory arteries. To See Editorial Commentary, pp 1117-1118Abstract-Blood pressure response to renal denervation is highly variable, and the proportion of responders is disappointing.This may be partly because of accessory renal arteries too small for denervation, causing incomplete ablation. Renal nerve stimulation before and after renal denervation is a promising approach to assess completeness of renal denervation and may predict blood pressure response to renal denervation. The objective of the current study was to assess renal nerve stimulation-induced blood pressure increase before and after renal sympathetic denervation in main and accessory renal arteries of anaesthetized patients with drug-resistant hypertension. The study included 21 patients. Nine patients had at least 1 accessory renal artery in which renal denervation was not feasible. Renal nerve stimulation was performed in the main arteries of all patients and in accessory renal arteries of 6 of 9 patients with accessory arteries, both before and after renal sympathetic denervation. Renal nerve stimulation before renal denervation elicited a substantial increase in systolic blood pressure, both in main (25.6±2.9 mm Hg; P<0.001) and accessory (24.3±7.4 mm Hg; P=0.047) renal arteries. After renal denervation, renal nerve stimulation-induced systolic blood pressure increase was blunted in the main renal arteries (Δ systolic blood pressure, 8.6±3.7 mm Hg; P=0.020), but not in the nondenervated renal accessory renal arteries (Δ systolic blood pressure, 27.1±7.6 mm Hg; P=0.917). This residual source of renal sympathetic tone may result in persistent hypertension after ablation and partly account for the large response variability. (Hypertension.

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Section: Discussionmentioning

confidence: 84%

Persistent Increase in Blood Pressure After Renal Nerve Stimulation in Accessory Renal Arteries After Sympathetic Renal Denervation

et al. 2016

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“…To date, there has been no examination of kidneys from patients who have undergone catheter-based RDN, only a recent case study investigating perivascular nerves 12 days after RDN showing that renal nerve damage was limited to an area 2 mm from the vascular lumen. 29 In a study in rats, 12 weeks after surgical denervation there was immunohistochemical evidence of reinnervation of renal afferent and efferent nerves 14 and functional reinnervation has been shown 8 weeks after surgical denervation in rats.…”

Section: Discussionmentioning

confidence: 99%

“…29 In a study in rats, 12 weeks after surgical denervation there was immunohistochemical evidence of reinnervation of renal afferent and efferent nerves 14 and functional reinnervation has been shown 8 weeks after surgical denervation in rats. 15 These studies concur with our findings that reinnervation of afferent and efferent renal nerves after catheter-based RDN is almost complete by 5.5 months and seems to be complete by 11 months after denervation.…”

Section: February 2015mentioning

confidence: 99%

Reinnervation of Renal Afferent and Efferent Nerves at 5.5 and 11 Months After Catheter-Based Radiofrequency Renal Denervation In Sheep

et al. 2015

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T here is extensive evidence that renal afferent and efferent nerves play a critical role in the control of renal function and in setting the level of arterial blood pressure.1 This includes the findings that in experimental and human hypertension there are increases in renal sympathetic nerve activity (RSNA) and renal norepinephrine spillover, respectively. In addition, surgical renal denervation (RDN) reduces blood pressure in hypertensive animals and patients, 1-4 although in patients this was associated with several side effects. 4 The development of catheter-based radiofrequency RDN has resulted in a resurgence of interest in RDN as a treatment for resistant hypertensive patients. Initial trials demonstrated reductions in office systolic blood pressure 5,6 and in the 36-month follow-up from the first trial 93% of patients showed reductions in office systolic blood pressure of ≥10 mm Hg after RDN. 7 In contrast, the recent Symplicity HTN-3 trial did not demonstrate reductions in systolic blood pressure beyond that observed in sham control patients 6 months after RDN, 8 although there is still debate on factors that may have led to the lack of effect, such as procedural and population variability.It would be expected that destruction of the renal nerves reduces blood pressure because the efferent renal nerves play a major role in stimulating renin release, causing renal vasoconstriction and inducing sodium retention.1 It is also plausible that in hypertension, increased afferent renal nerve activity may cause a reflex increase in sympathetic outflow and worsening hypertension.9,10 Such actions are supported by findings that in some hypertensive patients, catheter-based RDN reduced the level of muscle SNA 11,12 and plasma norepinephrine. 13 Despite these proposed mechanisms, it is unknown how Abstract-Previous studies indicate that catheter-based renal denervation reduces blood pressure and renal norepinephrine spillover in human resistant hypertension. The effects of this procedure on afferent sensory and efferent sympathetic renal nerves, and the subsequent degree of reinnervation, have not been investigated. We therefore examined the level of functional and anatomic reinnervation at 5.5 and 11 months after renal denervation using the Symplicity Flex catheter. In normotensive anesthetized sheep (n=6), electric stimulation of intact renal nerves increased arterial pressure from 99±3 to 107±3 mm Hg (afferent response) and reduced renal blood flow from 198±16 to 85±20 mL/min (efferent response). In a further group (n=6), immediately after denervation, renal sympathetic nerve activity was absent and the responses to electric stimulation were abolished. At 11 months after denervation (n=5), renal sympathetic nerve activity and the responses to electric stimulation were at normal levels. Immunohistochemical staining for renal efferent (tyrosine hydroxylase) and renal afferent nerves (calcitonin gene-related peptide), as well as renal norepinephrine levels, was normal 11 months after denervation. Findings at 5.5...

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“…31 Unfortunately, to date, RDN has been performed unguided, mostly using unipolar electrodes, in the absence of a straightforward method, allowing quantification of the renal sympathetic traffic before RDN and assessment of the completeness of renal nerve ablation after RDN. We hypothesized that periprocedural high-frequency RNS could be an attractive candidate to address both issues.…”

Section: Discussionmentioning

confidence: 99%

Renal Nerve Stimulation–Induced Blood Pressure Changes Predict Ambulatory Blood Pressure Response After Renal Denervation

et al. 2016

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R enal denervation (RDN) has been reported as a successful treatment of resistant hypertension in multiple trials studying the efficacy of RDN. [1][2][3][4][5][6] The sham-controlled Symplicity Hypertension-3 (HTN-3) trial, however, failed to show significant RDN-induced changes in blood pressure (BP) versus control, 7 raising serious doubts about the efficacy of RDN. 8-11Variable effects of RDN on BP have been reported, with a wide spectrum ranging between nonresponse to marked reduction in BP. 12 The absence of an ablation procedural end point for RDN is a potential explanation for variable responses, and the successful implementation of a reliably predictable end point could improve procedural success and clinical response.Recently, we reported on the feasibility of high-frequency electric renal nerve stimulation (RNS) in patients with resistant hypertension and demonstrated that RNS-induced BP increase was significantly blunted after RDN. 13 We hypothesized that the difference between RNS-induced BP rise before and after RDN could be used as a procedural end point for RDN and may prove a reliable functional test to predict BP response to RDN. The main goal of the current analysis was to investigate the 24-hour ambulatory BP changes after RDN and the relation to RNS before and after RDN. Methods PatientsAll patients with treatment-resistant hypertension referred for RDN between May 2014 and February 2015 were screened for inclusion in the RNS study. Patients were eligible if they were on a stable Abstract-Blood pressure (BP) response to renal denervation (RDN) is highly variable and its effectiveness debated. A procedural end point for RDN may improve consistency of response. The objective of the current analysis was to look for the association between renal nerve stimulation (RNS)-induced BP increase before and after RDN and changes in ambulatory BP monitoring (ABPM) after RDN. Fourteen patients with drug-resistant hypertension referred for RDN were included. RNS was performed under general anesthesia at 4 sites in the right and left renal arteries, both before and immediately after RDN. RNS-induced BP changes were monitored and correlated to changes in ambulatory BP at a follow-up of 3 to 6 months after RDN. RNS resulted in a systolic BP increase of 50±27

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Limited destruction of renal nerves after catheter-based renal denervation: results of a human case study

Cited by 80 publications

References 6 publications

Persistent Increase in Blood Pressure After Renal Nerve Stimulation in Accessory Renal Arteries After Sympathetic Renal Denervation

Persistent Increase in Blood Pressure After Renal Nerve Stimulation in Accessory Renal Arteries After Sympathetic Renal Denervation

Reinnervation of Renal Afferent and Efferent Nerves at 5.5 and 11 Months After Catheter-Based Radiofrequency Renal Denervation In Sheep

Renal Nerve Stimulation–Induced Blood Pressure Changes Predict Ambulatory Blood Pressure Response After Renal Denervation

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