Effect of kidney denervation on Muscle Sympathetic Nerve Activity in patients with chronic kidney disease (Sub-study multi-center randomized trial SIMPLICITY)

Chronic elevation of sympathetic nervous system activity has been identified by
extensive preclinical and clinical literature as a common and key factor in
disease states such as hypertension. The kidney sympathetic nerves are a major
contributor to the complex pathophysiology of elevated sympathetic nervous
system activity and hypertension. Therapeutic kidney denervation, the
deliberate disruption of the nerves connecting the kidneys with the central
nervous system, has been shown to be an effective means of modulating elevated
sympathetic nerve activity. The effect of kidney denervation on systolic blood
pressure and safety of denervation during three year follow up will be studied
in a multi-center randomized trial called SIMPLICITY. As our department will
be participating in the multi-center randomized trial the protocol of the study
is submitted to the Ethics Committee at the UMC Utrecht. This proposal is a
sub-study of SIMPLICITY study. The goal of the sub-study (mono-center study) is
to investigate the effect of kidney denervation on muscle sympathetic nerve
activity (MSNA).
In the past years, we have conducted studies using the microneurographic
technique in order to evaluate various questions relating hemodynamics in
kidney patients. This technique is considered one of the few reliable methods
to quantify sympathetic activity. MSNA is the centrally originated
postganglionic sympathetic nerve activity directed towards the resistance
vasculature. It is usually measured in the peroneal nerve. We have extensively
shown that MSNA is higher in hypertensive patients with chronic kidney disease
than in controls and that presently advised medical treatment reduce but not
normalize MSNA.

In the present study, we want to investigate the effect of kidney denervation
on MSNA in hypertensive patients. The central hypothesis of this project is
that MSNA in hypertensive patients will decrease (or may be even normalize as
in bilaterally nephrectomized patients) after kidney denervation.

In detail description of study protocol

First visit:
The patient will be asked to provide written informed consent form and his/her
eligibility for enrolment into the trial will be checked. Physical examination
will be performed. An appointment will be made for the first MSNA measurement
before kidney denervation.

Second visit:
The first MSNA measurement will be performed. This visit will take
approximately an hour.

Third visit:
This visit will take place at least 4 weeks after the kidney denervation
procedure. We have chosen for four weeks because then this appointment can be
combined with the visit for SIMPLICITY study.
All medications will be continued during the whole study.

There are no interventions in this study.

Microneurography: there are no risks associated with this procedure. Usually,
nerve recordings cause minimal discomfort and negligible, transient
after-effects, when studies are done by an experienced technician.