Relevance of Renal Denervation in Untreated Hypertensive Patients

Introduction

Hypertension is one of the main culprits of heart attack, stroke, and death. Blood pressure medications may not be as effective in preventing adverse events in hypertension. Most patients might still have elevated blood pressure, do not take the medication regularly, or experience side effects. Therefore, the search for non-drug treatment has led to research on renal denervation for untreated hypertension.

What Is Renal Denervation?

Renal denervation is a procedure where a catheter is passed through the femoral artery to reach the renal artery. The sympathetic renal nerves are ablated (removed surgically) with radiofrequency energy. Renal denervation can benefit patients with:

1. Poorly controlled blood pressure even with multiple drugs.

2. Individuals with adverse reactions to multiple drugs.

3. Patients who are unwilling to take blood pressure-controlling drugs.

What Is the Type of Renal Denervation?

Three approaches are being developed and are:

1. Radiofrequency Ablation: The technique uses a catheter to position electrodes necessary for generating heat using medium-frequency alternating current. The energy field can extend to a kidney lumen of 7 mm (millimeter). The kidney arterial wall tolerates heat well but is toxic to nerves in the energy field.

2. Ultrasound: In this approach, ultrasound sources are loaded upon a catheter with an inflatable balloon system. It allows the irrigation of the kidney arterial wall close to the catheter with a solution that remains cooler in the kidney lumen than in the perivascular space.

3. A tiny catheter with a concentrically placed microneedle is inserted into the femoral artery. When the catheter reaches the desired position, the microneedles are extended, penetrating the kidney artery into perivascular space. A small amount of neurotoxin is injected into the perivascular space through this microneedle simultaneously.

How Effective Is Renal Denervation in Untreated Hypertension?

Kidneys regulate blood pressure by absorbing excess water and salt from the body. When the sympathetic nerves in the arteries lead to the kidney becoming overactive, it could cause high blood pressure. Renal denervation uses radiofrequency energy to overactive nerves in the kidney to reduce their activity. After three months of the procedure, patients with untreated hypertension demonstrated a significant reduction in their blood pressure over 24 hours. With progressive intense stimulation of sympathetic nerves, there is increased renin release with low stimulation levels, intermediate stimulation reduces sodium excretion, and renal vascular resistance is increased at higher levels.

Renal denervation can be an effective alternative treatment approach to medication use. Studies on renal denervation have shown that it reduces blood pressure during the day, night, and early morning when the risk for adverse effects is heightened. During these times, there is a reduction in the efficacy of medication and blood pressure levels. The procedure requires hospitalization and is performed under local anesthesia.

What Are the Limitations to Renal Denervation Procedures Obtained From Clinical Trials?

The limitations are:

• Variations in Renal Anatomy: Anatomic variations in accessory renal arteries cause difficulty ablating these vessels. The energy can be targeted to proximal arteries, resulting in variation in treatment response.

• Improper Energy Delivery: The renal artery is close to the renal vein and para-aortic vessels. There could be a washout of thermal energy due to the proximity to these vessels.

• Limitation of Radiofrequency Energy Delivery: It causes thermal damage to endothelial tissue. There is potential for developing char and coagulum with non-irrigated catheter use. If the lesion is more distal, it can cause complete occlusion of vessels. Therefore, alternative methods to avoid vessel occlusion must be formulated.

What Is the Long-Term Efficacy of Renal Denervation?

The long-term efficacy of renal denervation is being studied under sham trials. However, the symplicity trials have demonstrated a sustained reduction in blood pressure for over three years. In animal studies, the affected sympathetic efferent and sensory afferent renal nerves regrow after renal denervation.

Currently, there is no evidence that nerves in the kidney regrow. However, based on the studies conducted on transplanted kidneys, it is concluded that kidney nerves do regrow. However, the functional efficacy of the nerves has not been fully realized. Therefore, this could be a limitation for renal denervation procedures.

What Are the Other Benefits of Renal Denervation?

Renal denervation effects on controlling hypertension are known. However, the procedure has other benefits that include:

• Managing arrhythmia.

• Premature Ventricular Contraction Mediated Cardiomyopathy: Renal denervation prevents cardiac fibrosis development and risk of ventricular failure by inhibiting the renin-angiotensin-aldosterone system (RAAS) and sympathetic activity.

• Ventricular Tachycardia Storm: After the renal denervation, there was a significant reduction in ventricular tachyarrhythmias in patients with a therapy-resistant electrical storm.

• Atrial Arrhythmia: In patients with obstructive sleep apnea, there was attenuation in the duration and incidence of atrial fibrillation following renal denervation. The procedure was as efficient as pharmacotherapy.

• Reduced Stroke Risk: In animal studies, there was a reduced risk of stroke in hypertensive rats. In addition to blood pressure reduction, oxidation stress and inflammation of the brain showed attenuation. It also enhanced cerebral blood flow and inhibited blood-brain barrier disruption.

• Treatment of Type 2 Diabetes: Renal denervation affects glucose metabolism and insulin resistance, improving insulin. The procedure can have a synergetic effect on medication by improving insulin sensitivity.

• Obstructive Sleep Apnea: In 80 percent of hypertensive patients, obstructive sleep apnea is noticeable. The condition can be a result of increased sympathetic tone. In a few studies, renal denervation has been shown to reduce severity of sleep apnea.

• Pulmonary Hypertension: Renal denervation reduces the RAAS and sympathetic outflow. The procedure improved pulmonary vascular remodeling and reduced right ventricular afterload.

• Gestational Hypertension: The expression of several RAAS components is reversed by renal denervation. The study was conducted on rats with gestational hypertension.

• Reduction in Renal Fibrosis: The chronic activation of the RAAS system can increase sodium reabsorption, which could cause renal or myocardial fibrosis. Renal denervation procedures can significantly reduce RAAS and sympathetic nervous system activity. It reduces collagen synthesis and the risk of cardiac or renal fibrosis.

Conclusion

Renal denervation is a procedure that is still under research. The blood pressure reduction potential of the procedure is comparable to that of anti-hypertensive medication. The procedure is safe and effective in animal studies. Successful clinical trials of renal denervation can provide an alternative approach for hypertensive treatment.