Renal Denervation

Nephrologists are well aware that stimulation of the renal sympathetic nerves causes increased renin release, increased sodium reabsorption, and a reduction of renal blood flow. These elements of the neural homeostatic regulation of kidney function may be overstimulated, resulting in chronically heightened sympathetic tone in hypertensive patients. Therapeutic denervation may also become an option for refractory hypertension.

The “Symplicity” technique uses a catheter inserted into the renal artery via the femoral artery to deliver radiofrequency energy to ablate the renal sympathetic nerve. The Symplicity HTN-1 study included 153 patients treated with this technique at 19 centers in Australia, Europe, and the United States.8,9

At baseline, the study population had a mean age of 57 years; 39% of subjects were women, 31% were diabetic, and 22% had coronary artery disease. They had a mean office BP of 176/98 mm Hg and were on a mean of five antihypertensive medications. Subjects had a mean estimated glomerular filtration rate of 83 mL/min/1.73 m2.


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The median time from first to last radiofrequency energy ablation was 38 minutes. The procedure was without complication in 97% of patients (149 of 153). Four acute procedural complications occurred, including three groin pseudoaneurysms and one renal artery dissection, all managed without further sequelae. Automated clinic pressure with printout (the primary trial endpoint) was reduced by 20/10, 24/11, 25/11, 23/11, 26/14, and 32/14 mm Hg at 1, 3, 6, 12, 18, and 24 months, respectively. These findings support the short-term safety and efficacy treatment of resistant hypertension with catheter-based renal sympathetic denervation.

The Symplicity HTN-2 randomized unblinded trial of renal sympathetic denervation versus usual care for medication-resistant hypertension show a significant reduction in systolic and diastolic blood pressure at six months compared with age-matched, equally hypertensive controls.

Although office-based BP measurements provided the sole assessment of BP as a primary endpoint, this intragroup variability of BP assessment requires further explanation, particularly because 35% of controls enjoyed a 10 mm Hg or more decrease in systolic pressure at six months. The major limitations of Symplicity HTN 1 and 2 studies are the absence of data beyond 36 months. There is speculation that functional renal sympathetic reinervation may occur, but there is no evidence of this up to three years post procedure.

The Symplicity HTN-3 is a randomized blinded trial of renal sympathetic denervation versus usual care for medication-resistant hypertension. This will be the largest of the 3 trials recruiting 542 patients in the United States and recruitment is ongoing. Results from this trial should be available early next year.

The overall evidence suggests that both BAT and renal denervation can safely reduce SBP in patients with resistant hypertension. Unfortunately, most of the clinical trials with both approaches have avoided patients with Stages 3b or higher CKD. Future clinical trials will address the limitations and long-term outcomes of these therapies to further define their potential therapeutic roles.

References

  1. Snyder JJ, Collins AJ. KDOQI hypertension, dyslipidemia, and diabetes care guidelines and current care patterns in the United States CKD population: National Health and Nutrition Examination Survey 1999-2004. Am J Nephrol 2009;30:44-54.
  2. Chobanian AV, Bakris GL, Black HR, et al, The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: the JNC 7 report. JAMA 2003;289:2560-2572.
  3. National Kidney Foundation, K/DOQI Clinical Practice Guidelines on Hypertension and Antihypertensive Agents in Chronic Kidney Disease. Am J Kidney Dis 2004;43(suppl 1):S1-S290.
  4. Upadhyay A, Earley A, Haynes SM, et al. Systematic review: blood pressure target in chronic kidney disease and proteinuria as an effect modifier. Ann Intern Med 2011;154:541-548.
  5. Peralta CA, Norris KC, Li S, et al. Blood pressure components and end-stage renal disease in persons with chronic kidney disease: The Kidney Early Evaluation Program (KEEP). Arch Intern Med 2012;172:41-47.