Is the failure of SYMPLICITY HTN-3 trial to meet its efficacy endpoint the “end of the road” for renal denervation?

Epstein, Murray; Marchena, Eduardo de

doi:10.1016/j.jash.2014.12.002

Cited by 36 publications

(26 citation statements)

References 37 publications

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“…Animals received Cefazolin as prophylaxis (1 g IM). At the terminal time point (7,30 or 90 days), animals were heparinized (200U/kg IV) and following final renal angiography and prior to euthanasia, a midline laparotomy was performed and fresh renal cortical tissues harvested for norepinephrine analysis ( Figure 2). Animals that received 2 treatment cycles were not subjected to cortical tissue harvest procedures ( Figure 2).…”

Section: Animal Model and Interventional Proceduresmentioning

confidence: 99%

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Sub-acute Safety and Efficacy Evaluation of Single versus Double Treatment Cycles of a Monopolar Radiofrequency Catheter-Based Renal Nerve Ablation and its Chronic Evolution in a Large Animal Model

Hubbard¹,

Sakaoka²,

Brants³

et al. 2016

J.ATAMIS

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Aims:We aimed to evaluate the transcatheter renal denervation(RDN) effects delivered by a mono-electrode catheter in a large animal model including safety implications of delivery of one cycle versus two cycles of ablations.Methods and Results:18 animals underwent bilateral RDN; 4 untreated naïve swine were enrolled as controls for norepinephrine levels(NE) only. Animals recieved 120-second (follow up-7,30 and 90 days) or 240-second cycles ablations (follow up-7 days). Norepinephrine evaluation, histology and immunohistochemistry evaluation was performed. No luminal obstruction was observed at follow up. A 70% decrease in NE levels (76.68±57.87ng/g) was observed at 7 days, 81% at 30 days(49.05±45.81ng/g), and 51% at 90 days(12.7±73.2 ng/g) compared to naïve controls(254.1±54.1ng/g;p<0.05). Histologically, the thermal effect extended to a complete circumferential involvement with a depth ~8mm. The primary histological feature at 7 days was nerve necrosis and distal atrophy; at 30 days, necrosis was replaced by healing changes of fibrosis. Neuromatous regeneration was apparent at 30 days at RF treated levels. At 90 days these features progressed to become more conspicuous. There were no appreciable differences in depth and circumferential extent of RF injury between one and two cycle treatment groups.Conclusion:RDN performed with a mono-electrode catheter (Iberis) appears to be safe following single or double-cycle RF ablation.NE decrease following RDN was demonstrated at 7, 30, and 90 days compared to naïve controls, suggesting efficient nerve ablation with the device as intended for human use.

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Section: Animal Model and Interventional Proceduresmentioning

confidence: 99%

“…The resulting tissue slices were dehydrated in ascending concentrations of alcohol and embedded in paraffin (Figure 2c, 2d). Serial 5 µm sections were stained with hematoxylin and eosin (H&E) and Elastic Trichrome (ET) for each time point (7,30 and 90 days).…”

Section: Tissue Preparation For Histology and Immunohistochemical Anamentioning

confidence: 99%

Sub-acute Safety and Efficacy Evaluation of Single versus Double Treatment Cycles of a Monopolar Radiofrequency Catheter-Based Renal Nerve Ablation and its Chronic Evolution in a Large Animal Model

Hubbard¹,

Sakaoka²,

Brants³

et al. 2016

J.ATAMIS

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“…However, recent clinical investigations on randomized renal denervation trials known as "symplicity HTN-3" have shown that renal denervation has limited efficacy [81,82] . These investigations, however, are subject to criticism and more studies will be needed to assess the benefits of renal denervation [83] .…”

Section: Transportmentioning

confidence: 99%

New insights into sodium transport regulation in the distal nephron: Role of G-protein coupled receptors

Morla

Edwards

Crambert

2016

WJBC

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The renal handling of Na + balance is a major determinant of the blood pressure (BP) level. The inability of the kidney to excrete the daily load of Na + represents the primary cause of chronic hypertension. Among the different segments that constitute the nephron, those present in the distal part (i.e ., the cortical thick ascending limb, the distal convoluted tubule, the connecting and collecting tubules) play a central role in the fine-tuning of renal Na + excretion and are the target of many different regulatory processes that modulate Na + retention more or less efficiently. G-protein coupled receptors (GPCRs) are crucially involved in this regulation and could represent efficient pharmacological targets to control BP levels. In this review, we describe both classical and novel GPCR-dependent regulatory systems that have been shown to modulate renal Na + absorption in the distal nephron. In addition to the multiplicity of the GPCR that regulate Na + excretion, this review also highlights the complexity of these different pathways, and the connections between them.

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“…My earlier study of the pathogenesis of the hepatorenal syndrome attributed many of the systemic and renal hemodynamic alterations to elevated sympathetic tone (20,21). More recently, I have participated in the recent renaissance of investigative interest in renal sympathetic activity in the context of patients with resistant hypertension (22). So over my extended career in academic medicine, my clinical investigative interests have been linked repeatedly with Josep Trueta's innovative and visionary proposals relating to both the renal circulation and also to renal sympathetic activation.…”

Section: A Personal Perspectivementioning

confidence: 99%

A forgotten chapter in the history of the renal circulation: the Josep Trueta and Homer Smith intellectual conflict

Epstein

Eknoyan

2015

American Journal of Physiology-Renal Physiology

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Is the failure of SYMPLICITY HTN-3 trial to meet its efficacy endpoint the “end of the road” for renal denervation?

Cited by 36 publications

References 37 publications

Sub-acute Safety and Efficacy Evaluation of Single versus Double Treatment Cycles of a Monopolar Radiofrequency Catheter-Based Renal Nerve Ablation and its Chronic Evolution in a Large Animal Model

Sub-acute Safety and Efficacy Evaluation of Single versus Double Treatment Cycles of a Monopolar Radiofrequency Catheter-Based Renal Nerve Ablation and its Chronic Evolution in a Large Animal Model

New insights into sodium transport regulation in the distal nephron: Role of G-protein coupled receptors

A forgotten chapter in the history of the renal circulation: the Josep Trueta and Homer Smith intellectual conflict

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