Resistant Hypertension in Chronic Kidney Disease

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therapy in an investigation to determine the association between adherence to anti-
hypertensive treatment and BP control in hypertensive outpatients, and 40 patients
(11.1%) met criteria for RHT. “Pseudo-resistance” is commonly misdiagnosed as
resistant hypertension, so in that sample, 98 of the 157 (62.4%) patients who showed
uncontrolled BP with the correct antihypertensive treatment were nonadherers and
therefore could be diagnosed as patients with resistant hypertension. This data indi-
cated that nonadherence is an important although lesser known problem with
patients suffering from RHT. These data indicate that nonadherence is an important,
yet lesser known, problem among patients with RHT.  Prior studies on resistant
hypertension are limited by the failure to apply a uniform definition of resistant
hypertension, a lack of longitudinal blood pressure data, and an inability to identify
“pseudo-resistant” hypertension due to poor medication adherence, according to
Daugherty et al. [ 18 ]. Because of this, trained pairs of pharmacy students and health
community agents used a standardized protocol to measure BP with the values of
systolic (SBP) and diastolic (DBP) blood pressure being obtained by the mean of
six blood pressure measurements, carried out by the research team during three
visits over a 2 week period, using mercury sphygmomanometers calibrated with a
minimum interval of 10 min between each double measurement. The measurements
were taken at the patients’ homes with the effect being the reduction of the influence
of the white-coat effect [ 19 ]. A validated Portuguese version of the eight-item
Morisky Medication Adherence Scale (MMAS-8) was used to assess adherence
[ 20 ]. If the patients had a score greater or equal to 6  in the MMAS-8, they were
considered to be adherent in this study [ 21 ]. Each patient supplied informed con-
sent, and the study protocol and consent form was approved by the Federal
University of Alagoas’ institutional review board. As the self-reporting methods
have a major limitation in underestimating the number of nonadherent individuals,
the proportion of nonadherent patients could be even higher. The adherence behav-
ior of patients and potential reasons for nonadherence can be gained from self-
reporting scales as they are usually simple, rapid, noninvasive, and economical in
their methods. An objective technique that is used to assess drug intake in these
cases of apparent resistant hypertension is toxicological urine screenings. Since the
1980s, there has been a systematic development of the analytical procedures for a
general toxicological screening in urine, first using gas chromatography–mass spec-
trometry (GC–MS) [ 22 , 23 ]. The development of analytical procedures for the
detection of various drug classes [ 24 , 25 ] including antihypertensive drugs [ 26 , 27 ]
is thanks to the recent improvement of liquid chromatography–mass spectrometry
(LC–MS) instrumentation. Individuals with a lower quality of life in terms of health
are more likely to have lower adherence to antihypertensive medications, and there-
fore the diagnosis of resistant hypertension should fundamentally include investiga-
tion of nonadherence and its causes [ 28 ]. This may result in the successful treatment
of hypertension as well as avoiding the expense and invasive therapeutic approaches
that include excessive antihypertensive therapy (although polypharmacy is difficult
to avoid because blood pressure can be controlled by using one drug in only about
50% of patients [ 17 ], electrical stimulation of carotid baroreceptors, catheter-based
renal denervation, and recent drug therapies (e.g., selective endothelin type A


N. Keles et al.
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