The morphological substrate for Renal Denervation: Nerve distribution patterns and parasympathetic nerves. A post-mortem histological study

Amsterdam, Wouter A. C. van; Blankestijn, Peter J.; Goldschmeding, Roel; Bleys, Ronald L. A. W.

doi:10.1016/j.aanat.2015.11.004

Cited by 50 publications

(32 citation statements)

References 31 publications

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“…Ultrastructural studies using electron microscopy techniques have shown that renal nerve fibers innervate epithelial cells of proximal tubules, the glucose reabsorption region of the kidney (Mather and Pollock 2011;Muller and Barajas 1972;Luff et al 1992). Although studies have examined the distribution of renal nerves around the renal artery (Maeda et al 2014;Sakakura et al 2014;van Amsterdam et al 2016), we could not determine the renal nerve branches that innervate the proximal tubules in this study.…”

Section: Discussioncontrasting

confidence: 44%

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: Discussioncontrasting

confidence: 44%

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

et al. 2018

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“…Besides shown in present study, previous published researches also showed that catheter-based RDN could not only decrease the renal norepinephrine level but also simultaneously reduce the plasma norepinephrine concentrations35. It has been demonstrated that renal nerves consist of renal efferent sympathetic nerves and also the renal sensory afferent nerves40. Meanwhile, the research conducted by Bleys RL et al showed that renal efferent sympathetic nerves and renal sensory afferent nerves were mostly contained into the same nerve bundle traveling around in renal artery adventitia40.…”

Section: Discussionsupporting

confidence: 76%

“…It has been demonstrated that renal nerves consist of renal efferent sympathetic nerves and also the renal sensory afferent nerves40. Meanwhile, the research conducted by Bleys RL et al showed that renal efferent sympathetic nerves and renal sensory afferent nerves were mostly contained into the same nerve bundle traveling around in renal artery adventitia40. Therefore, catheter-based RDN is proposed to destroy both renal efferent sympathetic nerves and also the renal sensory afferent nerves by radiofrequency energy delivery.…”

Section: Discussionmentioning

confidence: 99%

Renal Artery Vasodilation May Be An Indicator of Successful Sympathetic Nerve Damage During Renal Denervation Procedure

Chen

et al. 2016

Sci Rep

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Autonomic nervous system plays a crucial role in maintaining and regulating vessel tension. Renal denervation (RDN) may induce renal artery vasodilation by damaging renal sympathetic fibers. We conducted this animal study to evaluate whether renal artery vasodilation could be a direct indicator of successful RDN. Twenty-eight Chinese Kunming dogs were randomly assigned into three groups and underwent RDN utilizing temperature-controlled catheter (group A, n = 11) or saline-irrigated catheter (group B, n = 11) or sham procedure (group C, n = 6). Renal angiography, blood pressure (BP) and renal artery vasodilation measurements were performed at baseline, 30-minute, 1-month, and 3-month after interventions. Plasma norepinephrine concentrations were tested at baseline and 3-month after intervention. Results showed that, in addition to significant BP reduction, RDN induced significant renal artery vasodilation. Correlation analyses showed that the induced renal artery vasodilation positively correlated with SBP reduction and plasma norepinephrine reduction over 3 months after ablation. Post hoc analyses showed that saline-irrigated catheter was superior to TC catheter in renal artery vasodilation, especially for the acute dilatation of renal artery at 30-minute after RDN. In conclusion, renal artery vasodilation, induced by RDN, may be a possible indicator of successful renal nerve damage and a predictor of blood pressure response to RDN.

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“…Two recent postmortem studies support the hypothesis that in renal arteries with a large diameter, renal nerve innervation is located further from the lumen, which would reduce efficacy of RFRD and require greater energy to produce significant ablation [19, 20]. The most recent study [20] again supports the growing body of evidence that the nerves are closer to the lumen in distal versus proximal regions. This increased knowledge of renal nerve anatomy will facilitate the refinement of current RFRD techniques, with future directions including RFRD at more distal locations and the adoption of a circumferential versus interrupted pattern of ablation.…”

Section: Renal Afferent and Efferent Nerve Distribution And Reinnervamentioning

confidence: 77%

“…Significantly, there was a difference observed in renal nerve anatomy between normotensive versus hypertensive subjects [18]. Two recent postmortem studies support the hypothesis that in renal arteries with a large diameter, renal nerve innervation is located further from the lumen, which would reduce efficacy of RFRD and require greater energy to produce significant ablation [19, 20]. The most recent study [20] again supports the growing body of evidence that the nerves are closer to the lumen in distal versus proximal regions.…”

Section: Renal Afferent and Efferent Nerve Distribution And Reinnervamentioning

confidence: 99%

Renal Afferents

2016

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Purpose of ReviewThe etiology of hypertension, a critical public health issue affecting one in three US adults, involves the integration of the actions of multiple organ systems, including the renal sympathetic nerves. The renal sympathetic nerves, which are comprised of both afferent (sensory input) and efferent (sympathetic outflow) arms, have emerged as a major potential therapeutic target to treat hypertension and disease states exhibiting excess renal sympathetic activity.Recent FindingsThis review highlights recent advances in both clinical and basic science that have provided new insight into the distribution, function, and reinnervation of the renal sympathetic nerves, with a focus on the renal afferent nerves, in hypertension and hypertension-evoked disease states including salt-sensitive hypertension, obesity-induced hypertension, and chronic kidney disease.SummaryIncreased understanding of the differential role of the renal afferent versus efferent nerves in the pathophysiology of hypertension has the potential to identify novel targets and refine therapeutic interventions designed to treat hypertension.

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The morphological substrate for Renal Denervation: Nerve distribution patterns and parasympathetic nerves. A post-mortem histological study

Cited by 50 publications

References 31 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

Renal Artery Vasodilation May Be An Indicator of Successful Sympathetic Nerve Damage During Renal Denervation Procedure

Renal Afferents

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