VEITHSymposium: The Sympathetic Nervous System and Denervation by Endovascular Renal Artery Radiofrequency Ablation

What is sympathetic renal denervation?

Sympathetic renal denervation is the process of targeting and ablating the nerves going to the kidney. It is a percutaneous procedure, performed with a radiofrequency ablation catheter in the renal arteries. Many cardiovascular diseases like hypertension and heart failure, and metabolic conditions such as metabolic syndrome, are associated with excessive sympathetic nervous system activity, which may be specifically targeting the kidney itself. If that is true, renal denervation could be a treatment for such diseases, as opposed to the current pharmacological strategies that target the entire sympathetic nervous system and result in accompanying side effects. 

What happens once you reach the renal artery and the ablation is delivered?

The basic concept involves the delivery of a standard radiofrequency energy that heats the tissue to a certain degree. The heat is what destroys the nerves, which travel in the walls of the artery. There are various catheter designs. The first is the Medtronic Symplicity catheter, a single-tip monopolar catheter used to ablate from in the lumen. It ablates 4-6 spots within the renal artery, in a spiral fashion. Other catheter designs have come out that are slightly different, but many of them are based on radiofrequency energy that heats the tissue and destroys the nerves. 

How much of the renal innervation is ablated? 

That is the challenge with the technique. In humans, right now there is no way to know. The theory is that all of the nerves travel through the adventitia of the renal artery and so will be targeted by the ablation, but we do not yet have a method of learning how many of those nerves are actually destroyed in the process. There is some debate about whether the goal should be ablation of all of the nerves to the kidney or just some of them. The guess, based on indirect measurements, is anywhere from 50-75% of the nerves are ablated in this procedure. 

You are a basic scientist, not an interventionalist. Can you share some of your research interests?

I study the role of the sympathetic nervous system in cardiovascular diseases. I have mainly studied hypertension, but also heart failure, in trying to understand what causes over-activity of the sympathetic nervous system in general and then also as this activity relates to specific organs in the body. The kidneys have received a great deal of attention in this area, although other organs are clearly important as well. We are trying to understand how overactivity of the sympathetic nervous system causes disease and then learn more about the ability to reverse disease through ablation procedures.

Can you describe how the kidneys tie into the central nervous system?

The nerves that go to the kidney are the efferent nerves. These are motor nerves that go from the central nervous system to the kidney, to control three basic kidney functions. One is the direct vasoconstriction of the renal vasculature by the release of the neurotransmitter norepinephrine. So these efferent (motor) nerves can increase renal vascular resistance, which can cause hypertension. Second, they directly innervate the tubules of the kidney and can cause the retention of sodium, a problem in heart failure and hypertension. Third and final, the efferent nerves stimulate the release of an enzyme, renin, from a specific part of the renal vasculature. Renin is the beginning of the cascade for the renin-angiotensin system, which is clearly involved in heart failure and hypertension. Indeed, many of the drugs we use to treat heart failure and hypertension inhibit the renin-angiotensin system. By ablating the efferent nerves instead, we are able to obtain the same effect, inhibiting the renin-angiotensin system. 

The other part of the story that is emerging, though, is the nerves that travel from from the kidney, the afferent (sensory) nerves, to the central nervous system, may be important. These renal sensory nerves can signal the central nervous system about changes in kidney function, that then influencing sympathetic nerves to all the other organs in the body. Data are suggesting that, in humans who have received renal nerve ablation treatment (thus far, only those with drug-resistant hypertension), we are seeing effects that are not explained by changes in kidney function that are due to loss of efferent nerves. For example, a decrease in plasma glucose, suggesting alterations in glucose metabolism, has been reported following renal nerve ablation. There are also reports of decreased frequency of arrhythmias and a decrease in sympathetic activity to skeletal muscle. That has researchers thinking that the effects may be even more complicated, but that it may be possible that renal nerve ablation has other beneficial effects that are a direct result of ablating the afferent or sensory nerves. 

Our basic research involves trying to understand the relative importance of ablating efferent versus afferent nerves. In animal models of cardiovascular disease (i.e., hypertension and heart failure), we have been developing methods to specifically target one set of nerves or the other. If we find that one classification of those nerves, say, the afferents, are important, we could improve the therapy by targeting only those nerves for ablation, leaving the efferent nerves to the kidney intact. 

What about safety?

Renal denervation appears to be a very safe procedure. The popularity of the technique is because of its potential benefit with essentially no side effects. It is being considered for its impact on not just hypertension, but heart failure, diabetes, and arrhythmias. 

However, at this point, we still have work to do. Another area of intense research is looking for a way to confirm the effectiveness of the ablation at the time of the procedure. Currently, we wait to see the effects after the procedure to confirm it was completed properly. 

Disclosure: Dr. John Osborn reports he is a paid consultant for Medtronic.

John W. Osborn, PhD, can be contacted at osbor003@umn.edu.

Suggested reading

1. Schlaich MP, Esler MD, Fink GD, Osborn JW, Euler DE. Targeting the sympathetic nervous system: critical issues in patient selection, efficacy, and safety of renal denervation. Hypertension. 2013; Published online before print December 9 2013, doi:10.1161/HYPERTENSIONAHA.113.02144.