161Resistant Hypertension and Chronic Kidney Disease
Ten years ago this issue was already thoroughly investigated, given that in CKD
hypertension becomes more and more resistant to various treatments along the evo-
lution of the pathogenic complex in each case. Because of the high complexity of
the relation between CKD and hypertension, that we have just mentioned, hyperten-
sion in CKD has a very intricate pathogenesis [ 57 ]. Our understanding at that time
was mainly based on a couple of traditional explanations (high volemia due to
sodium and water retention; activation of the renin-angiotensin-aldosterone system
(RAAS)), but other mechanisms were also considered, such as increased sympa-
thetic activity, high endothelin production and/or decreased availability of
endothelium- derived relaxing factors (EDRFs), arterial remodeling, renal ischemia,
and sleep apnea [ 57 ]. Thus, autonomic dysfunction, with a focus on sympathetic
overactivation, was already discussed at that time as possibly involved in hyperten-
sion pathogenesis, in general and in CKD in particular.
A rather simple terminological delineation helped in finding out that in CKD the
pseudoresistance of hypertension to medication predicts renal outcome but is not
associated with increased cardiorenal risk, while true resistance is prevalent and iden-
tifies patients with the highest CVD risk [ 58 ]. Here we use the term of resistant hyper-
tension to generically designate a decreased efficiency of traditional antihypertensive
remedies, but we emphasize the constant efforts of the medical community toward
enhanced terminological precision in using such terms, e.g., resistant hypertension vs.
refractory hypertension and controlled hypertension vs. uncontrolled hypertension
[ 59 ]. Under such circumstances we consider that explicit reference to the antihyper-
tensive scheme and to the determined vs. targeted ABP values should be made when-
ever appropriate in the context. We mention that hypertension control in CKD was
found to be poor in the USA 10 years ago, mainly due to systolic hypertension [ 59 ].
Sympathetic Overactivation, Resistant Hypertension,
and Chronic Kidney Disease
General aspects regarding sympathetic activity in hypertension have already been
presented in this chapter (sections “Influence of Renal Sympathetic Nerve Activity
on Blood Pressure Control by the Kidneys”, “Sympathetic Overactivation in
Resistant Hypertension”, and “Non-pharmacological Suppression of Sympathetic
Activity in Hypertension”), so here below we focus just on sympathetic overactiva-
tion in CKD (Fig. 10.1).
About 20 years ago the evidence for sympathetic overactivity in CKD started
accumulating rather quickly, but it was still not clear if reducing sympathetic over-
activity could be therapeutically relevant [ 57 , 60 ]. Starting with the simple further
reduction of glomerular filtration rate (GFR), by preferential constriction of afferent
vs. efferent arterioles, various mechanisms were known by which chronic sympathetic
10 Secondary Causes: Work-Up and Its Specificities in CKD: Influence of Autonomic...