Renal denervation for the treatment of resistant hypertension: review and clinical perspective

Abstract

When introduced clinically 6 years ago, renal denervation was thought to be the solution for all patients whose blood pressure could not be controlled by medication. The initial two studies, SYMPLICITY HTN-1 and HTN-2, demonstrated great magnitudes of blood pressure reduction within 6 mo of the procedure and were based on a number of assumptions that may not have been true, including strict adherence to medication and absence of white-coat hypertension. The SYM-PLICITY HTN-3 trial controlled for all possible factors believed to influence the outcome, including the addition of a sham arm, and ultimately proved the demise of the initial overly optimistic expectations. This trial yielded a much lower blood pressure reduction compared with the previous SYMPLICITY trials. Since its publication in 2014, there have been many analyses to try and understand what accounted for the differences. Of all the variables examined that could influence blood pressure outcomes, the extent of the denervation procedure was determined to be inadequate. Beyond this, the physiological mechanisms that account for the heterogeneous fall in arterial pressure following renal denervation remain unclear, and experimental studies indicate dependence on more than simply reduced renal sympathetic activity. These and other related issues are discussed in this paper. Our perspective is that renal denervation works if done properly and used in the appropriate patient population. New studies with new approaches and catheters and appropriate controls will be starting later this year to reassess the efficacy and safety of renal denervation in humans. denervation; hypertension; pathophysiology; renal nerves; resistance RESISTANT HYPERTENSION IS defined as failure to achieve a guideline-driven blood pressure of less than 140/90 mmHg in patients who are adherent to maximally tolerated doses of at least three antihypertensive drugs, including a diuretic appropriate for kidney function (13). Population-based studies published over the last decade indicate that anywhere from 3 to 12% of hypertensive patients in the United States have resistant hypertension, despite the abundance of efficacious blood pressure-lowering agents belonging to over seven drug classes (11,20,68). Moreover, in addition to the cardiovascular mortality risk directly linked to the extent of blood pressure elevation, resistant hypertensive patients frequently have additional risk factors such as obesity, diabetes, chronic kidney disease, and age over 55 and are therefore more likely to die from stroke, myocardial infarction, heart failure, and end-stage renal disease (47, 76).Since increased sympathetic activity was believed to be present in many patients with resistant hypertension, renal denervation was thought to be the solution for all patients whose blood pressure could not be controlled by medication and was introduced for clinical use 6 years ago. In the open label, uncontrolled SYMPLICITY HTN-1 and SYMPLICITY HTN-2 trials, undertaken in patients with resistant hypertension, redu...

Prolonged Baroreflex Activation Abolishes Salt-Induced Hypertension After Reductions in Kidney Mass

“…38–39 This sympathetically-mediated impairment of renal excretory function is normally achieved by promoting sodium reabsorption directly and indirectly through stimulation of the renin-angiotensin-aldosterone system. 38,39 In this regard, our previous studies during suppression of sympathetic activity by BA have emphasized the importance of neurally-mediated inhibition of renin secretion in counteracting pressure-dependent renin release and permitting chronic lowering of arterial pressure. 38 However, as the renin-angiotensin system is suppressed during HS, we reasoned that attenuation of the direct effects of neurally-mediated tubular sodium reabsorption may be sufficient to reduce arterial pressure during baroreflex-induced sympathoinhibition.…”

“…28–30,32,33 However, the subsequent unabated fall in arterial pressure to control levels throughout the 7 days of BA, with the maintenance of sodium balance, indicates persistent effects of BA to increase renal excretory function. Had BA not had powerful sustained effects to promote sodium excretion, initial reductions in arterial pressure would have been markedly diminished, 35,38,39 such as when the natriuretic effects of BA are opposed by inappropriately high plasma levels of either ANG II or aldosterone during chronic infusion of these potent antinatriuretic hormones. 29,33,38 Thus, an important finding in this study was that BA abolished the salt-sensitive hypertension associated with a marked reduction in functional nephrons.…”

Mechanisms of sodium balance: total body sodium, surrogate variables, and renal sodium excretion

“…The present review is focused on the interaction between cardiovascular, hormonal, and renal mechanisms of sodium homeostasis under normal conditions in large animals and in humans. Although important to the regulation of sodium excretion and blood pressure, the function of the renal nerves is not included; several recent reviews provide excellent coverage (95,105,111,130).…”

JALA Special Issue: High-Throughput Imaging

“…A prime example of imageguided therapy, renal denervation commonly involves the use of a guided catheter that emits a radio frequency toward the intimal walls of the renal artery to ablate the renal nerve and reduce blood pressure. 34,35 Because this technique is still in the early stages of adoption, there are a number of devices that are competing to become the standard in renal denervation. A key aspect of many of these devices lies in the miniaturization of various components into the form and function of catheters in order to deliver a radio frequency or ultrasonic wave suitable for renal nerve ablation.…”