The dreams of renal denervation: a translational approach

Abstract

In the body, many processes are carried out without raising conscious sensations. The activities of these processes are controlled by a special system of nerve cells and nerve fibers: the sympathetic nervous system (SNS) and the parasympathetic nervous system (PSNS).

In addition to the beneficial effects of the SNS, the sympathetic nervous system also plays a role in the etiology of a number of cardiovascular diseases such as primary hypertension, heart failure, chronic kidney disease, diabetes, and obesity. Renal denervation (RDN) has been developed as a new treatment option to lower the activity of the SNS and may therefore be an alternative treatment for patients with resistant hypertension. Next to the blood pressure reduction induced by renal denervation, some small studies have reported that RDN can positively affect other conditions characterized by sympathetic overactivity. These conditions include heart failure and insulin resistance.

The purposes of this thesis were to understand the working mechanism behind renal denervation (RDN), to determine which patients benefit most from treatment, and to study the effects of RDN. The first focus is on the pathophysiologic studies of the working mechanism behind RDN and possible markers of successful therapy. The second focus is on the selection of eligible patients for RDN. The third focus is on the effects of RDN in hypertensive patients. The fourth focus is on the effects of RDN beyond resistant hypertension.

The conclusions of this thesis are:

1. Renal denervation may induce hemodynamic changes in the kidneys itself, resulting in a lower resistance in the kidneys. It may be expected that this lower resistance leads to an improved renal blood flow and therefore a lower blood pressure. It may even be that hemodynamic measurements may be used as a per-procedural marker of successful RDN.

2. This thesis showed that a multidisciplinary team improves the selection of eligible patients for RDN. Since a relevant number of patients referred for RDN is not eligible for treatment, all patients should be screened systematically. Moreover we demonstrated that patients with an impaired renal function benefit more from treatment.

3. In the third part of this thesis it is concluded that the effects of RDN have a wide variety and that a relevant number of patients is a non-responder after RDN.

4. Finally it was investigated what the effects of renal denervation was on disease-states other than (resistant) hypertension. It was concluded that renal denervation does not have a significant effect on insulin resistance in a metabolic population.

In conclusion, renal denervation still seems a very promising therapy. However, we should not be blinded by the first, very encouraging, studies. It is likely that a blood pressure reduction can be established, however not to such an extent as suggested in the first clinical studies.