Endovascular Renal Denervation

Endovascular renal denervation has emerged as a promising therapy for resistant hypertension. Phase III randomized trials have not been completed, but the emerging data suggest that this procedure may be highly effective at improving hypertension control in this population. The procedure is also being evaluated for a variety of other clinical indications characterized by increased sympathetic activity. The pathophysiologic rationale for this approach, the early experience with this technique, and alternative methods that are being developed deserve note by clinicians treating patients who have resistant hypertension.

Resistant Hypertension and the Role of Sympathetic Nervous System

Resistant hypertension, defined as persistent elevation of blood pressure above goal despite concurrent use of three antihypertensive agents at target dose (with one being a diuretic), is surprisingly common. It is estimated that 10% to 15% of hypertensive adult patients in the United States have resistant hypertension. An equally large percentage of patients have uncontrolled hypertension caused by inadequate or inappropriate pharmacotherapy, intolerance or noncompliance with therapy, or failure to diagnose secondary causes of hypertension.

The pivotal role of the sympathetic nervous system as an important mediator of hypertension has been recognized for more than half a century. One of the early treatments for hypertension was thoracolumbar sympathectomy, which was effective at controlling hypertension and was associated with an improved survival in patients with malignant hypertension. The procedure was accompanied by significant side effects such as postural hypotension, syncope, and erectile dysfunction and was abandoned soon after emergence of pharmacologic treatment for hypertension. Many of the commonly used antihypertensive drugs affect the sympathetic system at various levels, and increased sympathetic nerve activity is present in most hypertensive patients.

The role of renal autonomic innervation in hypertension has emerged as an important area of investigation. The kidney has a rich sympathetic and a sparse parasympathetic innervation. The role of the parasympathetic nervous system on renal physiology is poorly understood. The postganglionic sympathetic nerve fibers richly innervate the efferent and afferent renal arterioles, the juxtaglomerular apparatus, and the renal tubular system. An increase in efferent signals (from the central nervous system to the kidney) results in renal vasoconstriction, decreased renal blood flow, increased renin release, and sodium and volume retention. Afferent signals (from the kidney to the central nervous system) disinhibit the vasomotor center in the medulla, resulting in increased efferent signals to the kidneys, heart, and peripheral blood vessels, which results in sustained high blood pressure.

The renal sympathetic fibers travel in the adventitia of the renal artery, and all the current approaches to renal denervation involve nonselectively denervating the kidney by ablating the renal artery adventitia ( Figure 1 ). The most commonly used approach involves radiofrequency (RF) ablation, although ultrasonic, laser, and chemical ablation have also been evaluated in human and animal studies. The currently used methods ablate both afferent and efferent fibers, and the clinical impact of the technique reflects the effect of total renal denervation.