Resistant Hypertension in Chronic Kidney Disease

71

this cohort is likely due to selection of a healthier community-dwelling population
with high rates of undertreatment exemplified by about 40% of the cohort still hav-
ing uncontrolled hypertension on ≤2 drug after 4  years. Consistent with several
other studies, the authors found a prevalence of aTRH about twice as high in partici-
pants with than without CKD.  The novelty of this study lies in the finding that a
rapid decline in kidney function was associated with a greater risk of new-onset
aTRH independent of eGFR level and other major risk factors for RH. This rein-
forces the likelihood that CKD is both a cause and consequence of RH.

Clinical Outcomes from Primary or Post Hoc Analyses

of Randomized Clinical Trials

A post hoc analysis of the Antihypertensive and Lipid-Lowering Treatment to
Prevent Heart Attack Trial (ALLHAT) evaluated the impact of baseline aTRH on
incidence of cardiovascular and renal outcomes [ 19 ]. Trial participants were ran-
domly allocated to treatment with amlodipine, chlortalidone, or lisinopril with dose
titration and addition of further antihypertensive drugs using a prespecified proto-
col. Based on the year 2 study visit (1996–2000), 13% (n = 1870) of 14,684 trial
participants were characterized as having aTRH defined by office BP greater than
140/90 mmHg despite three or more antihypertensive medications or requiring four
or more antihypertensive medications irrespective of BP. No ABPM were available
to exclude pseudoresistance due to white coat hypertension. The aTRH group were

Table 5.3 Significant associations of kidney function at baseline and kidney function decline rate
with new-onset apparent treatment-resistant hypertension in the Three-City Study [ 21 ]

Adjusted ORs

aTRH vs persistent

cHT

aTRH vs persistent
ucHT
All participants at baseline n = 162 vs 620 n = 162 vs 1054
Male 2.44 [1.67–3.55] 0.98 [0.69–1.38]
Body mass index ≥30 Kg/m^2 1.57 [1.02–2.40] 1.69 [1.14–2.52]
Diabetes 3.31 [2.12–5.16] 2.26 [1.53–3.35]
History of CVD 0.75 [0.44–1.28] 1.86 [1.12–3.09]
Participants with eGFR measured at 4 years n = 74 vs 269 n = 74 vs 433
Male sex 2.24 [1.29–3.91] 1.11 [0.66–1.86]
Diabetes 3.15 [1.60–6.21] 1.93 [1.06–3.51]
eGFR decline ≥3 mL/min/1.73 m^2 per year 1.89 [1.09–3.29] 1.99 [1.19–3.35]
eGFR decline ≥5 mL/min/1.73 m^2 per year 2.78 [1.33–5.81] 2.91[1.49–5.70]
All analyses were adjusted for center
Abbreviations: aTRH incident apparent treatment-resistant hypertension, cHT controlled hyper-
tension, ucHT uncontrolled hypertension with two antihypertensive drugs, OR odds ratios, CI 95%
confidence interval, eGFR glomerular filtration rate estimated using the MDRD equation, MDRD
Modification of Diet in Renal Disease, CVD cardiovascular disease

5 Resistant Hypertension and Outcomes in Patients with and Without Chronic Kidney...