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Treatment of Resistant Hypertension
Medical Treatment
The approach to treatment of resistant hypertension in patients with CKD should
have objective to address the multitude of factors that contribute to the pathogenesis
of hypertension in this population, including disturbed handling of sodium and vol-
ume expansion, increased activity of the renin–angiotensin–aldosterone system
(RAAS), improved sympathetic activity, and declined endothelium-dependent
vasodilatation. Specific focus should be on the patterns of elevated blood pressure
that have been discovered to be more prevalent in this population and to enhance the
risk of target organ damage, including elevated nighttime BP and the presence of
non-dipping.
Volume
Salt restriction has been indicated to lower blood pressure in patients with and with-
out hypertension. In the Dietary Approaches to Stop Hypertension (DASH)-Sodium
trial, sodium reduction from 100 to 50 mmol per day generally had twice the effect
on blood pressure as reduction from 150 to 100 mmol per day [ 72 ]. The effect of
dietary sodium restriction on the degree of BP reduction seems to be particularly
powerful in patients with resistant hypertension. In a small, randomized crossover
trial of patients with resistant hypertension, a low (50 mmol/day) compared with
high (250 mmol/day) sodium diet diminished mean office SBP by 22.7 mmHg and
initiated significant declines in daytime, nighttime, and 24-h ambulatory blood pres-
sure [ 32 ]. For that reason, patients with resistant hypertension, as well as those with
CKD, show salt-sensitive hypertension. Patients with CKD have an impaired skill
to effectively excrete sodium and will reply to a sodium load by increasing blood
pressure for reconstructing salt balance; this “pressure natriuresis” arrives at the
expense of hypertension-related target organ damage [ 73 ]. Besides, dietary sodium
intake has been indicated to interact with the RAAS, especially aldosterone, in both
animal models and human studies, to mediate hypertension, vascular and tissue
damage, and kidney disease [ 74 ]. In a study of patients with resistant hypertension
and high 24-h urinary aldosterone, urinary protein excretion increased considerably
with progressively greater salt intake, putting forward that aldosterone excess and
high dietary sodium intake interact to increase proteinuria [ 75 ]. In fact, in a random-
ized, double-blind, placebo-controlled crossover study in proteinuric patients with-
out diabetes, salt restriction itself exerted an antihypertensive and antiproteinuric
effect and further enhanced the antiproteinuric effects of RAAS blockade to almost
the same magnitude as, and in an additive manner with, diuretics [ 76 ]. While this
study and others have showed the beneficial impact of sodium restriction on inter-
mediate renal outcomes in CKD, it is significant to address that no large cohort
studies have indicated sodium restriction to decline BP or long-term cardiovascular
N. Keles et al.