Renal Sympathetic Denervation for the Treatment of Difficult-to-Control or Resistant Hypertension

Abstract

Hypertension represents a major health problem with an appalling annual toll. Despite the plethora of antihypertensive drugs, hypertension remains resistant in a considerable number of patients, thus creating the need for alternative strategies, including interventional approaches. Recently, catheter-based renal sympathetic denervation has been shown to be fairly safe and effective in patients with resistant hypertension. Pathophysiology of kidney function, interaction and crosstalk between the kidney and the brain, justifies the use of renal sympathetic denervation in the treatment of hypertension. Data from older studies have shown that sympathectomy has effectively lowered blood pressure and prolonged life expectancy of hypertensive patients, but at considerable cost. Renal sympathetic denervation is devoid of the adverse effects of surgical sympathectomy, due to its localized nature, is minimally invasive, and provides short procedural and recovery times. This paper outlines the pathophysiological background for renal sympathetic denervation, describes the past and the present of this interventional approach, and considers several future potential applications.

Figures

Figure 1

Demonstrates pathophysiology of resistant hypertension. Increased sympathetic outflow is a fundamental abnormality in most patients.

Figure 2

Long-term blood pressure control following surgical sympathectomy.

Figure 3

Blood pressure and heart rate reduction using baroreceptor stimulation therapy (BST) from 1 to 3 volts. Note that acutely blood pressure was reduced from 210/96 to 144/66 and heart rate from 71 to 50 beats per minute.

Figure 4

Sympathetic fibers, both efferent and afferent, are found in the adventitia of renal arteries. These fibers can be ablated using specialized catheters that deliver radiofrequency energy.

Figure 5

Schematic representation of sympathetic innervations of the kidney.

Figure 6

Afferent and efferent sympathetic innervations of the kidney.

Figure 7

Blood pressure response following bilateral renal sympathetic denervation using a radiofrequency ablation catheter.

Figure 8

Noradrenalin spillover of both the right and the left kidneys at baseline and 30 days after sympathetic renal denervation.

Figure 9

Results of microneurography before and after renal nerve ablation. Panel (a) shows the results of bilateral renal denervation, as assessed by the radiotracer dilution method, at baseline and 30 days after the procedure. After ablation, decreases in renal norepinephrine spillover were observed in both kidneys (48% in the left kidney and 75% in the right kidney), indicating substantial modulation of renal sympathetic efferent nerve activity after the procedure. Simultaneously, a marked reduction in whole-body sympathetic nerve activity was apparent, with a decrease in whole-body norepinephrine spillover of 42% (b). Panel (c) shows a reduction in muscle sympathetic-nerve activity (MSNA), as assessed in the peroneal nerve on microneurography, after bilateral renal nerve ablation, which highlights the possibility that inhibition of afferent renal-nerve activity may contribute to the reduction in central sympathetic drive.