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magnitude of blood pressure reduction following renal denervation may be inde-
pendent of the level of salt intake. This possibility has not yet been tested in humans,
however.
In addition to efferent sympathetic activity, the renal nerves also convey afferent
signals from renal mechano- and chemoreceptors. Stimulation of renal chemorecep-
tors in response to ischemic metabolites and/or uremic toxins activates a sympatho-
excitatory reflex. This reflex has been postulated to contribute to the excessive
adrenergic drive found in several forms of hypertension, including resistant hyper-
tension, and provided a conceptual basis for a putative effect of renal denervation to
suppress sympathetic activity to other territories in addition to the kidneys [ 5 ].
However, clinical studies are inconsistent in ascertaining sustained reductions in
muscle sympathetic nerve activity following renal denervation [ 33 , 36 ]. Progressive
renal injury in patients with CKD and resistant hypertension may however deter-
mine a more complete manifestation of this renal afferent sympathoexcitatory
reflex, amenable to inhibition by renal denervation. This possibility remains unre-
solved since clinical trials of renal denervation have consistently excluded patients
with overt impairment of renal function [ 36 ]. Thus, based on the currently available
data, the antihypertensive effects of renal denervation are likely determined for the
most part by interruption of efferent sympathetic traffic to the kidney.
Aspects of Sympathetic Activation in Resistant Hypertension
Associated with CKD
Chronic kidney disease (CKD) is a complex pathological condition, whereby the
vast majority of chronic renal failure cases evolve with chronic increase in arterial
blood pressure (BP) in the systemic circulation, e.g., with hypertension. The latter
favors multiple detrimental mechanisms, which ultimately lead to the various com-
plications that define a global picture of chronic cardiovascular disease (CVD). This
picture is superimposed over that of chronic renal failure, and there are various ways
the involved pathological mechanisms are potentiating each other, by multiple
vicious circles. Therefore, a major therapeutic aim in the evolution of CKD is to
improve control of BP and hence to reduce CVD morbidity and mortality in this
high-risk population, facing the frequent situation of hypertension resistant to clas-
sical antihypertensive drugs and their associations.
Due to such important issues, the complex relations involving CKD, hyperten-
sion, and autonomic dysfunction have been under increasingly intense investigation
and debate over the last two decades. Quite many reviews have been published in
this expanding area, including most recent ones focused right on the subject of this
section, e.g., on CKD and specifically one of the following: resistant hypertension
[ 50 – 52 ] sympathetic overactivity, including baroreflex dysfunction [ 53 , 54 ]; arterial
stiffness [ 55 ]; and clinical imaging of arterial calcification [ 56 ].
R. Iliescu and D.N. Şerban