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Definition of Resistant Hypertension and Incidence in CKD
Resistant hypertension is a condition when BP is not controlled despite maximal
effective dosing of ≥3 medications of different classes; one is being a diuretic [ 7 ].
Resistant hypertension should not be confused with pseudoresistance.
Pseudoresistance implies uncontrolled office BP while receiving ≥3 medications in
the setting of medication nonadherence, improper BP measurement technique, and/
or white coat HT. It is suggested that pseudoresistance is suggested to contribute to
as much as 50% of RHT [ 8 ]. Factors associated with pseudoresistance include use
of cuffs in an inappropriate size, recent smoking, improper BP measurement tech-
nique, inappropriate drug combinations and doses, poor compliance by patients to
the prescribed antihypertensive regimen, poor doctor-patient relationship, and poor
education of patients to the significance of achieving goal BP [ 9 ]. Thus it is impor-
tant to differentiate true RHT or pseudoresistance while evaluating the patients and
performing investigations.
Resistant hypertension is either not to be confused with refractory HT. Refractory
HT is a condition which meet the definition of RHT but BP is not controlled despite
maximal medical therapy (i.e., ≥4 antihypertensive medications at maximal effec-
tive dosing and of different class) [ 10 , 11 ]. This means that patients with RHT may
achieve target BP, patients with refractory HT cannot achieve optimal BP [ 12 ]. A
part from RHT, one of the important concepts is masked hypertension (MHT) in
CKD. This is important since as many as 40–70% of patients with CKD present
MHT and MHT is related also with RHT [ 4 , 13 ]. Masked hypertension was defined
as controlled office BP (<140/90 mm Hg) with an elevated overall average BP by
24-h ABPM (>130/80 mm Hg) or home BP > 135/85 mm Hg [ 14 ].
Despite all these confirmed data, there is only scarce data regarding epidemiol-
ogy of RHT both in general and CKD population. This is due to fact that until a few
years ago, information regarding the epidemiology of RHT was obtained from indi-
rect sources, such as cross-sectional studies on hypertension control in large cohorts
from tertiary hypertension centers and outcome trials in hypertension. However,
during recent years, large population- based studies have provided direct epidemio-
logic data on RHT and estimated its prevalence at 8–12% of adult patients with
hypertension. Chronic kidney disease in particular has been long considered a fre-
quent underlying cause of RHT; however, recently, direct epidemiologic data for this
entity in patients with CKD were brought to light again, suggesting an even higher
prevalence of resistant hypertension (approximately 20–35%) among such individu-
als. In one study which specifically focused on RHT in CKD, De Nicola et al. dem-
onstrated that in 300 hypertensive CKD patients, 38% had RHT after 6 months of
BP management, with a higher prevalence of diabetic nephropathy and higher levels
of proteinuria with RHT [ 15 ]. Furthermore, recent prospective cohort studies have
suggested incident RHT to be associated with increased cardiovascular and renal
risk in both the general hypertensive population and patients with CKD [ 9 ].
Thus it is of no question that RHT is prevalent and has potential impact on
cardiovascular outcomes in patients with HT including CKD.
B. Afsar and A. Kirkpantur