123I-mIBG scintigraphy: Clinical tool for assessing renal sympathetic activity?

Abstract

See related article, pp. 363-371Among patients with treatment-resistant hypertension, transcatheter renal denervation has been shown to reduce blood pressure (BP) in a number of uncontrolled, unblinded clinical trials.1 However, in a prospective, single-blind, randomized trial that compared transcatheter renal denervation to a sham procedure, there was no significant difference in systolic BP between the two treatment arms at 6 months follow-up.2 Proposed reasons for the lack of benefit include a substantial placebo effect related to the procedure, differences in medication adherence such that the sham-treated control group may have taken more antihypertensive medications, operator inexperience with transcatheter renal denervation, and performance of an inadequate number of ablations in each renal artery.3 It has been postulated that operator inexperience and performance of too few ablations may have led to incomplete denervation and therefore an inadequate BP response to the procedure. The absence of a readily available methodology to define completeness of transcatheter renal denervation in humans remains as an unmet need in defining the potential role of the procedure in clinical practice.The contribution of increased renal sympathetic tone to the pathophysiology of hypertension has been known for decades. Surgical renal denervation in hypertensive animal models has been shown to cause significant decreases in BP compared to sham controls. 4 A commonly employed method of surgical denervation involves stripping the adventitia from the renal artery of hypertensive rats and exposing the artery to phenol, a compound that irreversibly blocks neural conduction. 5Renal norepinephrine (NE) content measured at specified time points after surgical denervation in hypertensive rats has been shown to decrease dramatically (94% reduction compared to sham-controlled rats at 1 week; P \ 0.001), suggesting complete ablation of the renal nerves. A positive correlation was also shown between absolute change in BP after denervation and renal NE content in denervated animals (r = 0.80, P \ 0.001). 4In the clinical research setting, a number of methods have been utilized to assess the completeness of renal denervation in hypertensive humans. The most promising and best characterized are the measurements of muscle sympathetic nerve activity (MSNA), renal NE spillover rate, and assessment of sympathetically mediated responses to electrical stimulation of the renal artery before and after denervation.6-8 Assessment of MSNA is minimally invasive and entails percutaneous insertion of a recording electrode into a superficial nerve (peroneal or radial), allowing direct recording of postganglionic sympathetic neural bursts. MSNA reflects moment-to-moment sympathetic outflow from the central nervous system to either skeletal muscle or skin, but does not provide direct information on sympathetic outflow to the kidney or heart. 9Renal NE spillover is assessed by infusing small doses of radiolabeled NE intravenously and measuring its level in...