Renal denervation to treat resistant hypertension: Guarded optimism
ABSTRACTRenal sympathetic denervation has shown promise in treating hypertension resistant to drug therapy. This procedure lowers blood pressure via targeted attenuation of renal sympathetic tone, and it has a favorable safety profile. But although there is reason for cautious optimism, we should keep in mind that the mechanisms of hypertension are complex and multifactorial, and further study of this novel therapy and its long-term effects is needed.
KEY POINTS
- Renal sympathetic nerves help regulate volume and blood pressure as they innervate the renal tubules, blood vessels, and juxtaglomerular apparatus. They carry both afferent and efferent signals between the central nervous system and the kidneys.
- Surgical sympathectomy was done in the 1950s for malignant hypertension. It had lasting antihypertensive results but also caused severe procedure-related morbidity. A new percutaneous procedure for selective renal denervation offers the advantage of causing few major procedure-related adverse effects.
- Selective renal denervation decreases norepinephrine spillover and muscle sympathetic nerve activity, evidence that the procedure reduces sympathetic tone.
- The major clinical trials done so far have found that renal denervation lowers blood pressure significantly, and the reduction is sustained for at least 3 years.
CATHETER-BASED RENAL DENERVATION
Renal sympathetic nerves run through the adventitia of the renal arteries in a mesh-like pattern.
In the renal denervation procedure, a specially designed catheter is inserted into a femoral artery and advanced into one of the renal arteries. There, radiofrequency energy is applied to the endoluminal surface according to a proprietary algorithm, thereby delivering thermal injury selectively to the renal sympathetic nerves without affecting the abdominal, pelvic, or lower-extremity nerves. The energy delivered is lower than that used for cardiac electrophysiologic procedures.
The nerves are not imaged or mapped before treatment. The procedure is performed on both sides, with four to six sites ablated in a longitudinal and rotational manner in 2-minute treatments at each site, to cover the full circumference (Figure 1).
In the United States, the device (Symplicity Renal Denervation System; Medtronic, Inc, Mountain View, CA) is available only for investigational use.
Below, we briefly review the studies of renal denervation to date. SYMPLICITY HTN-1 Symplicity HTN-1 was a proof-of-principle study in 45 patients with resistant hypertension (Table 1).14,15
Effect on blood pressure. Six months after renal denervation, blood pressure was significantly lower than at baseline (−22/−11 mm Hg, 95% confidence interval [CI] 10/5 mm Hg) in 26 patients available for follow-up. At 12 months, the difference from baseline was −27/−10 mm Hg (95% CI 16/11 mm Hg) in 9 patients available for follow-up (Table 2).14
Evidence of the durability of blood pressure reduction came from an expanded cohort of 153 patients followed for 2 years after denervation.16
Further follow-up data showed a sustained and significant blood pressure reduction through 3 years after denervation (unpublished results presented at the 2012 annual meeting of the American College of Cardiology). Notably, patients who were initially considered to be nonresponders (defined as failure of their blood pressure to go down by at least 10 mm Hg) were all reported to have a clinical response at 36 months.
Adverse events. In the initial and expanded cohorts combined, one patient suffered a renal artery dissection due to manipulation of the guiding catheter before the radiofrequency energy was delivered, and three patients developed a femoral pseudoaneurysm. No other long-term arterial complications were observed.
Comments. Limitations of this study included a small number of patients, no control group, and a primary outcome of a reduction in office blood pressure rather than in ambulatory blood pressure.
Additionally, although the authors concluded that there was no significant deterioration in renal function during the study period, we should note that in an additional follow-up period in this cohort, 10 patients with available 2-year data had a decrease in estimated glomerular filtration rate (eGFR) of −16.0 mL/min/1.73 m2. In 5 patients who did not have spironolactone (Aldactone) or another diuretic added after the first year of followup, a lesser but significant decrease (−7.8 mL/min/1.73 m2) was noted. The investigators surmised that denervation may enhance diuretic sensitivity, leading to prerenal azotemia in some patients.17
