Renal sympathetic nerve activity after catheter-based renal denervation

Abstract

BackgroundCatheter-based renal sympathetic denervation (RDN) has been considered a potential treatment for therapy resistant hypertension (RHT). However, in a randomized placebo-controlled trial, RDN did not lead to a substantial blood pressure (BP) reduction. We hypothesized that variation in the reported RDN efficacy might be explained by incomplete nerve disruption as assessed by renal 123I–meta-iodobenzylguanidine (123I–mIBG) scintigraphy.MethodsIn 21 RHT patients (median age 60 years), we performed 123I–mIBG scintigraphy before and 6 weeks after RDN. Additionally, we assessed changes in BP (24 h day, night, and average), plasma- and urinary-catecholamines and plasma renin activity (PRA) before and after RDN. Planar scintigraphy was performed at 15 min and 4 h after 123I–mIBG administration. The ratio of the mean renal (specific) counts vs. muscle (non-specific) counts represented 123I–mIBG uptake. Renal 123I–mIBG washout was calculated between 15 min and 4 h.ResultsAfter RDN office-based systolic BP decreased from 172 to 153 mmHg (p = 0.036), while diastolic office BP (p = 0.531), mean 24 h systolic and diastolic BP (p = 0.602, p = 0.369, respectively), PRA (p = 0.409) and plasma catecholamines (p = 0.324) did not significantly change post-RDN. Following RDN, 123I–mIBG renal uptake at 15 min was 3.47 (IQR 2.26–5.53) compared to 3.08 (IQR 2.79–4.95) before RDN (p = 0.289). Renal 123I–mIBG washout did not change post-RDN (p = 0.230). In addition, there was no significant correlation between the number of denervations and the renal 123I–mIBG parameters.ConclusionsNo changes were observed in renal 123I–mIBG uptake or washout at 6 weeks post-RDN. These observations support incomplete renal denervation as a possible explanation for the lack of RDN efficacy.

Recent advances in radiotracers targeting norepinephrine transporter: structural development and radiolabeling improvements

“…Photon scattering from high liver radioactivity accumulation remains a challenge for the diagnosis of heart diseases (Kim et al 2010). Second, researches, such as 123 I-MIBG imaging involving therapy-resistant hypertension patients before and after catheter-based renal sympathetic denervation or kidney autotransplantation (Dobrowolski et al 2015(Dobrowolski et al , 2018, have proven the uptake of MIBG into kidney irrelevant to sympathetic nerve activity in the kidney, presumably due to its non-specific uptake via OCT2 or other transporters. Thus, a NET-selective tracer would open a new door for the diagnosis of renal sympathetic innervation.…”

Effects of catheter‐based renal denervation on renin‐aldosterone system, catecholamines, and electrolytes: A systematic review and meta‐analysis

“…Follow‐up duration ranged from 0.5 to 72 months. Ten studies reported data on plasma renin, 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 nine studies on plasma aldosterone, 14 , 15 , 16 , 18 , 19 , 21 , 22 , 23 , 24 two studies on plasma norepinephrine, 20 , 25 seven studies on serum sodium, 23 , 24 , 26 , 27 , 28 , 29 , 30 nine studies on serum potassium, 23 , 24 , 26 , 27 , 28 , 29 , 30 , 31 , 32 five studies on urinary sodium, 18 , 20 , 24 , 26 , 33 and two studies on urinary potassium. 24 , 26 The characteristics of included studies are summarized in Table 1 .…”

Effect of renal denervation on long-term outcomes in patients with resistant hypertension

“…The greater the plasma renin activity, the more obvious the antihypertensive effect [ 45 ]. More studies indicated plasma renin activity did not significantly change post-RDN [ 46 – 48 ]. RDN also reduced whole-body norepinephrine spillover [ 49 ], did not significantly change plasma catecholamines [ 46 ], and had a mixed influence on aldosterone [ 45 , 47 , 48 , 50 ].…”

“…More studies indicated plasma renin activity did not significantly change post-RDN [ 46 – 48 ]. RDN also reduced whole-body norepinephrine spillover [ 49 ], did not significantly change plasma catecholamines [ 46 ], and had a mixed influence on aldosterone [ 45 , 47 , 48 , 50 ]. In addition, arterial stiffness is a leading biomarker of risk in hypertension [ 51 ], and ferritin represents an independent risk factor of arterial stiffness [ 52 ].…”