Copyright © 2017 Wolters Kluwer Health, Inc. All rights reserved.
Hyper tensi on i n dialysis patients: a conse nsus
d ocum en t b y the E ur opean Ren al and Cardio v ascul ar
Medicine (EURECA-m) working group of the
European Renal Associa tion ^ European Dialysis and
Transplan t Associa tion (ERA-ED TA) and the
Hypertensio n and the Ki dn ey w o r king gro u p of th e
Eu ro pe an S oc iety o f Hyper tensi on (E SH)
Pantelis A. Sarafidis
a
, Alexandre Persu
b,c
, Rajiv Agarwal
d,e
, Michel Burnier
f
, Peter de Leeuw
g,h
,
Charles Ferro
i
, Jean-Michel Halimi
j
, Gunnar Heine
k
, Michel Jadoul
l
, Faical Jarraya
m,n
,
Mehmet Kanbay
o
, Francesca Mallamaci
p
, Patrick B. Mark
q
, Alberto Ortiz
r
, Gianfranco Parati
s,t
,
Roberto Pontremoli
u
, Patrick Rossignol
v,w
, Luis Ruilope
x
, Patricia Van der Niepen
y
,
Raymond Vanholder
z
, Marianne C. Verhaar
aa
, Andrzej Wiecek
bb
, Gregoire Wuerzner
f
,
Ge´rard M. London
cc
, and Carmine Zoccali
p
In patients with end-stage renal disease treated with
hemodialysis or peritoneal dialysis, hypertension is very
common and often poorly controlled. Blood pressure (BP)
recordings obtained before or after hemodialysis display a
J-shaped or U-shaped association with cardiovascular
events and survival, but this most likely reflects the low
accuracy of these measurements and the peculiar
hemodynamic setting related with dialysis treatment.
Elevated BP by home or ambulatory BP monitoring is
clearly associated with shorter survival. Sodium and volume
excess is the prominent mechanism of hypertension in
dialysis patients, but other pathways, such as arterial
stiffness, activation of the renin–angiotensin–aldosterone
and sympathetic nervous systems, endothelial dysfunction,
sleep apnea and the use of erythropoietin-stimulating
agents may also be involved. Nonpharmacologic
interventions targeting sodium and volume excess are
fundamental for hypertension control in this population. If
BP remains elevated after appropriate treatment of
sodium-volume excess, the use of antihypertensive agents
is necessary. Drug treatment in the dialysis population
should take into consideration the patient’s comorbidities
and specific characteristics of each agent, such as
dialysability. This document is an overview of the
Journal of Hypertension 2017, 35:657–676
a
Department of Nephrology, Hippokration Hospital, Aristotle University of Thessalo-
niki, Thessaloniki, Greece,
b
Pole of Cardiovascular Research, Institut de Recherche
Expe´ rimentale et Clinique,
c
Division of Cardiology, Cliniques Universitaires Saint-Luc,
Universite´ Catholique de Louvain, Brussels, Belgium,
d
Department of Medicine,
Indiana University School of Medicine,
e
Richard L. Roudebush Veterans Administration
Medical Center, Indianapolis, Indiana, USA,
f
Service of Nephrology and Hypertension,
Lausanne University Hospital, Lausanne, Switzerland,
g
Department of Medicine,
Maastricht University Medical Center, Maastricht,
h
Zuyderland Medical Center,
Geleen, The Netherlands,
i
Department of Renal Medicine, University Hospitals
Birmingham NHS Foundation Trust, Birmingham, UK,
j
Service de Ne´ phrologie-Immu-
nologie Clinique, Hoˆ pital Bretonneau, Franc¸ois-Rabelais University, Tours, France,
k
Saarland University Medical Center; Internal Medicine IV - Nephrology and Hyper-
tension, Homburg, Germany,
l
Division of Nephrology, Cliniques universitaires Saint-
Luc, Universite´ catholique de Louvain, Brussels, Belgium,
m
Department of Nephrology,
Sfax University Hospital,
n
Research Unit, Faculty of Medicine, Sfax University, Sfax,
Tunisia,
o
Division of Nephrology, Department of Medicine, Koc University School of
Medicine, Istanbul, Turkey,
p
CNR-IFC, Clinical Epidemiology and Pathophysiology of
Hypertension and Renal Diseases Unit, Ospedali Riuniti, Reggio Calabria, Italy,
q
Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow,
UK,
r
IIS-Fundacion Jimenez Diaz, School of Medicine, University Autonoma of Madrid,
FRIAT and REDINREN, Madrid, Spain,
s
Department of Cardiovascular, Neural, and
Metabolic Sciences, San Luca Hospital, Istituto Auxologico Italiano,
t
Department of
Medicine and Surgery, University of Milano-Bicocca, Milan,
u
Universita` degli Studi and
IRCCS Azienda Ospedaliera Universitaria San Martino IST, Genova, Italy,
v
INSERM,
Centre d’Investigations Cliniques Plurithe´ matique 1433, UMR 1116, Universite´de
Lorraine, CHRU de Nancy,
w
F-CRIN INI-CRCT Cardiovascular and Renal Clinical Trialists,
Nancy, France,
x
Hypertension Unit & Institute of Research iþ12, Hospital Universitario 12
de Octubre, Madrid, Spain,
y
Department of Nephrology and Hypertension, Universitair
Ziekenhuis Brussel - VUB, Brussels,
z
Nephrology Section, Department of Internal
Medicine, Ghent University Hospital, Gent, Belgium,
aa
Department of Nephrology
and Hypertension, University Medical Center Utrecht, Utrecht, The Netherlands,
bb
Department of Nephrology, Transplantation and Internal Medicine Medical University
of Silesia in Katowice, Katowice, Poland and
cc
Manhes Hospital and FCRIN INI-CRCTC,
Manhes, France
Correspondence to Pantelis A. Sarafidis, MD, MSc, PhD, Department of Nephrology,
Hippokration Hospital, Aristotle University Thessaloniki, Konstantinoupoleos 49,
GR54642 Thessaloniki, Greece. Tel: +30 2310 992796; fax: +30 2310 688969;
e-mail: psarafidis@auth.gr
This article has been co-published in Nephrology Dialysis Transplantation https://
academic.oup.com/ndt.
Received 13 November 2016 Accepted 10 January 2017
J Hypertens 35:657–676 Copyright ß 2017 Wolters Kluwer Health, Inc. All rights
reserved.
DOI:10.1097/HJH.0000000000001283
Journal of Hypertension www.jhypertension.com 657
Consensus Document
Copyright © 2017 Wolters Kluwer Health, Inc. All rights reserved.
diagnosis, epidemiology, pathogenesis and treatment of
hypertension in patients on dialysis, aiming to offer the
renal physician practical recommendations based on
current knowledge and expert opinion and to highlight
areas for future research.
Keywords: blood pressure, dry-weight, end-stage renal
disease, hemodialysis, hypertension, peritoneal dialysis,
sodium excess
Abbreviations: ABPM, ambulatory blood pressure
monitoring; ACEI, angiotensin-converting enzyme inhibitor;
ADMA, asymmetric dimethylarginine; AIx, augmentation
index; ALCHEMIST, ALdosterone Antagonist Chronic
HEModialysis Interventional Survival Trial; ARB, angiotensin-
II receptor blocker; BLOCADE, beta-blocker to LOwer
CArdiovascular Dialysis Events study; BP, blood pressure;
CAPD, continuous ambulatory peritoneal dialysis; CCB,
calcium channel blocker; CI, confidence interval; CKD,
chronic kidney disease; CRIC, Chronic Renal Insufficiency
Cohort study; DOHAS, Dialysis Outcomes Heart Failure
Aldactone Study; DOPPS, Dialysis Outcomes and Practice
Patterns Study; DRIP, Dry-Weight Reduction in
Hemodialysis Patients study; eGFR, estimated glomerular
filtration rate; eNOS, endothelial nitric oxide synthase; ERA-
EDTA, European Renal Association – European Dialysis and
Transplant Association; ESAs, erythropoietin-stimulating
agents; ESH, European Society of Hypertension; ESRD,
end-stage renal disease; EURECA-m, European Renal and
Cardiovascular Medicine Working Group; FOSIDIAL,
Fosinopril in Dialysis study; HDPAL, Hypertension in
Hemodialysis Patients Treated with Atenolol or Lisinopril
study; HR, hazard ratio; KEEP, Kidney Early Evaluation
Program; LUST, Lung Water by Ultra-Sound Guided
Treatment to Prevent Death and Cardiovascular
Complications in High Risk ESRD Patients with
Cardiomyopathy study; LV, left ventricular; LVH, left
ventricular hypertrophy; MRA, mineralocorticoid receptor
antagonist; NKF-KDOQI, National Kidney Foundation –
Kidney Disease Outcomes Quality Initiative; NO, nitric
oxide; OCTOPUS, Olmesartan Clinical Trial in Okinawa
Patients under Dialysis study; PP, pulse pressure; PRA,
plasma renin activity; PWV, pulse wave velocity; RAAS,
renin–angiotensin–aldosterone system; rhuEPO,
recombinant erythropoietin; RR, relative risk; TonEBP,
tonicity-responsive enhancer-binding protein; VEGF,
vascular endothelial growth factor
INTRODUCTION
I
n patients with end-stage renal disease (ESRD) receiv-
ing renal replacement therapy with hemodialysis or
peritoneal dialysis, hypertension is very common and
often inadequately controlled [1]. Elevated blood pressure
(BP), particularl y when recorded outside of the dialysi s unit
with home or ambulatory BP monitoring (ABPM), is directly
associated with shorter survival [2–4]. Sodium and volume
excess appear to be the most importa nt causes of hyper-
tension in dialysis patients; therefore, nonpharmacologic
strategies such as dietary sodium restriction, individualized
dialysate sodium prescription and gradual dry-weight
reduction should be the initial therapeutic approaches to
control BP [5,6], but this approach is often not adequately
implemented [7,8]. In patients who remain hypertensive
after management of sodium and volume excess, pharma-
cologic therapy is recommended to achieve BP control,
taking into account the pharmacologic characteristics of
each antihypertensive drug [5,6,9].
This is a docum ent prepared by experts from the Euro-
pean Renal and Cardiovascular Medicine (EURECA-m)
working group of the European Renal Association-Euro-
pean Dialysis and Transplant Association (ERA-EDTA) and
the Hypertension and the Kidney working group of the
European Society of Hypertension (ESH). It aims to sum-
marize current knowledge on the diagnosis, epidemiol ogy,
pathogenesis and treatment of hypertension in ESRD
patients on dialysis. As far as treatment is concern ed, we
discuss both nonpharmacological and pharmacological
strategies to manage hypertension. This document mainly
presents the evidence in patients receiving maintenance
hemodialysis treatment, because most of the current knowl-
edge derives from studies in this category of patients. Data
from the fewer relevant studies in peritoneal dialysis
patients are also discussed.
DIAGNOSIS OF HYPERTENSION IN
DIALYSIS PATIENTS
According to the 2004 National Kidney Foundation Kidney
Disease Outcomes Quality Initiative guidelines [10], hyper-
tension in hemodialysis patients is dia gnosed when pre-
dialysis BP is more than 140/90 mmHg or when postdialysis
BP is more than 130/80 mmHg, respec tively [10]. However,
the diagnosis of hypertension using conventional peridia-
lytic BP recordings may be problematic for several reasons
[11,12]. Predialysis and postdialysis BPs are recorded by
dialysis unit staff often without the necessary attention to
the standardization of the technique of BP measurement
and the prerequisites for objective office BP recordings [13].
BP measurements pre, during and postdialysis are not made
for diagnostic reasons but to exploit a major hemodynamic
metric like BP in order to assess cardiovascular stability
before, during and immediately after the dialysis pro-
cedure. Thus, using these readings to diagnose hyperten-
sion, assess the success of antihypertensive treatment or
examine future cardiovascular risk is inherently problem-
atic. Several factors may lead to inaccurate BP predialysis
and postdialysis readings, such as the white-coat effect,
limited time for relaxation – patient impatience to start
dialysis and leave the unit quickly – fear or anxiety for
correct arteriovenous fistula needling, previous bilateral
upper limb attempts of arteriovenous fistulae and unknown
validity of most oscillometric devices attached to commer-
cially available hemodialysis machines. Furthermore, truly
high BP variability (predialysis to postdialysis and day-by-
day variability) in response to fluctuations in volume status
and other parameters during the intradialyt ic and interdia-
lytic periods is another important issue that complicates the
accurate diagnosis of hypertension [14]. The typical pattern
of hemodynamic response to ultrafiltration is BP decrease
from predialysis to postdialysis; the magnitude of intra-
dialytic BP reduction is for the most part related to the
Sarafidis et al.
658 www.jhypertension.com
Volume 35 Number 4 April 2017
Copyright © 2017 Wolters Kluwer Health, Inc. All rights reserved.
magnitude and the rate of volume withdrawal during
dialysis. The converse phenomenon is observed during
the interdialytic interval [15], and several studies show that
interdialytic weight gain is closely associated with high er
predialysis BP [16]. The poor diagnostic accuracy of peri-
dialytic BP recordings is supported by a meta-analysis
showing that both predialytic and postdialytic BP readings
provide imprecise estimates of the mean interdialytic BP
recorded with 44-h ABPM [17]. Furtherm ore, in comparison
with interdialytic BP recordings, peridialytic BP recordings
have a weaker prognostic relationship with mortality in
hemodialysis patients [2,3,11]. It must be noted that it is not
known, whether peridialytic measurements following a
standardized technique would exhibit stronger prognostic
associations with outcome; preliminary evidence suggest
that this is not very likely since even when peridialytic BP is
recorded with a standardized protocol it relates poorly to
44-h ABPM values [18].
Due to the reasons described above, the rate of errors in
the diagnosis of hypertension when using peridialytic BP
measurements is unacceptably high [19]. The proportions of
chronic kidney disease (CKD) patients with white-coat and
masked hypertension are reported to be around 30 and 7%,
respectively, but they are suggested to be much higher in
people receiving dialysis [14,20–22]. An alternative can be
the use of an average of intradialytic BP measurements, as
in one study a median intradia lytic cutoff BP of 140/
90 mmHg during a mid-week dialysis session provided
greater sensitivity and specificity in detecting interdialytic
hypertension as compared with predialysis and pos tdialysis
BP measurements [23]. Yet, BP measurements obtained
outside of the dialysis unit are still needed to reliably
diagnose hypertension among dialysis patients. Home BP
monitoring is widely appl ied and strongly recommended
by international guidelines for the diagnosis and manage-
ment of hypertension in the general population [24]. Com-
pared with BP recordings obtained predialysis or
postdialysis, home BP exhibits stronger associations with
mean 44-h ambulatory BP [18,20]. In the Dry-Weight
Reduction in Hemodialysis Patients (DRIP) trial, changes
in home BP after 4 and 8 weeks of dry-weight probing (i.e.
supervised gradual dry-weight reduction) were closely
associated with the changes in 44-h ambulatory BP; in
contrast, predialysis and postdialysis BP recordings failed
to detec t the changes in ambulatory BP caused in response
to dry-weight reduction [25]. Moreover, home BP was
shown to have high short-term reproducibility from one
week to the next [20] in contrast to the high variability and
poor reproducibility of conventio nal peridialytic BP record-
ings [14]. Furthermore, home BP exhibits stronger associ-
ations with indices of target-organ damage [26–28] and
represents a more powerful predictor of future cardiovas-
cular events or all-cause mortality compared with the BP
measurements obtained within the dialysis unit [2,3,11]. It is
important to note that interdialytic BP recordings maintain
their strong prognostic association with cardiovascular out-
comes even when a small number (i.e. six) randomly
selected measurements are used to assess the interdialytic
BP burden [29]; thus, the location and time-frame covered
and not the number of BP recordings is the major factor
determining the strong prognostic significance of
interdialytic ambulatory BP measurements, although the
timing of BP recordings may be relevant for reproducibility
[30]. The notion that home BP is useful to guide the
management of hypertension in dialysis patients is sup-
ported by a pilot study that randomized 65 hypertensive
hemodialysis patients to have their antihypertensive drug
therapy adjusted either on the basis of routine predialytic
BP or with home BP monitoring. Over a mean follow-up of
6 months, a significant reduction in interdialytic ambulatory
BP of 9/7 mmHg was documented in the home BP-guided
group, but not in the predialytic BP-guided group [31].
Similar results were registered in another small randomized
trial in hemodialysis patients [32]. One important aspect,
however, is for future studies to gather data to provide
patients with a precise protocol on when and how often
home BP measurements should be performed as it is has
been done for hypertensive patients in the general popu-
lation [31].
Many authors suggest that ABPM is the ‘gold-standard’
method for diagnosing hypertension in patients receiving
dialysis [5,11,33,34]. The superiority of this approach over
the conventional peridialytic BP measurements is strongly
supported by comparative studies showing that mean 44-h
interdialytic BP is more strongly associated with the pres-
ence of target-organ damage [such as echocardiographic
left ventricular (LV) hypertrophy (LVH)] [26]. In addition,
observational studies clearly suggest that ABPM predicts all-
cause and cardiovascular mortality better than peridialytic
BP [2,4,11]. The use of ABPM has also the advantage of
recording BP during night-time, providing additional infor-
mation on the circadian variation of BP; the presence of a
nondipping nocturnal BP pattern is very common among
dialysis patients and has been associated with LVH [35] and
increased risk of all-cause and cardiovascular mortality [36].
The high prevalence of nondipping and nocturnal hyper-
tension among dialysis patients [12] suggests that the appli-
cation of ABPM for the diagnosis and the treatment of
hypertension is more compelling than in the general popu-
lation, where ABPM has already been strongly recom-
mended by the an ad-hoc ESH working group [37], NICE
guidelines [38] and the US preventive service [39]. The
thresholds to define hypertension using home and ABPM
[11] are summarized in Table 1. Of note, when neither
ABPM nor home BP measurements are applicable in dialy-
sis patients, the diagnosis and the management of hyper-
tension can be made on the basis of office BP
measurements taken during the dialysis interval, as a recent
study suggested that in contrast to predialysis BP that has a
U-shaped relationship with mortality, in the same patients
the average of three office measurements (obtained by
trained personnel from patients in the sitting position after
at least 5 min of quiet rest) is almost linearly related to this
risk [40]. The threshold of office BP (140/90 mmHg) recom-
mended by current guidelines for the definition of hyper-
tension in CKD patients [41] can be extended also to
hemodialysis patients; it has to be noted, however, that
the issue of the optimal BP in CKD is controversial [42] and
could be reexamined in the near future in view of recent
evidence [43].
Despite the above advantages, ABPM is still perceived as
a technique with limited applicability in dialysis patients.
Hypertension in dialysis patients
Journal of Hypertension www.jhypertension.com 659
Copyright © 2017 Wolters Kluwer Health, Inc. All rights reserved.
This reservation depends partly on the fact that a substantial
part of studies using ABPM in dialysis patients were per-
formed in a single American academic hemodialysis unit
[2,15,26], but also on the fact that ABPM is believed to be
uncomfortable and incon venient in a group of patients with
a high treatment burden, including a high proportion of
sleep disturbances, especially when applied for 48 h.
Furthermore, accurate ABPM readings could be challenging
in patients with bilateral upper limb attempts of arterio-
venous fistulae for dialysis access [11,45]. The fact that
ABPM is not reimbursed in many countries is another
obstacle to its wider use in hemodialysis. However,
additional research is needed to define the acceptability
of ABPM from the patients’ side, the best BP thresholds to
define hypertension, which may be different from those of
the general population because of the continuous shifts of
volume and other factors, the optimum frequency of its use,
and the cost-effectiveness of ABPM in the dialysis popu-
lation. Until ongoing studies investigating these issues will
be available, home BP appears as a simpler and more
efficient approach to measure BP and make therapeu tic
decisions in dialysis patients [19].
In contrast to the typical decline in BP during dialysis, in
approximately 10–15% of dialysis patients, BP exhibits a
‘paradoxical’ intradialytic elevation [46,47]. Although this
abnormal pattern of intradialytic hemodynamic response
has been long recognized, there definition of intradialysis
hypertension is still matter of debate. For example, in some
studies intradialysis hypertension was defined as a rise of at
least 15 mmHg in mean BP during dialysis [48] and in others
as a rise of at least 10 mmHg in SBP during dialysis or
immediately postdialysis in a certain number (most
commonly the last three or four out of the last six) of
dialysis treatments [46,47,49,50] or with the use of the
regression of all intradialytic BP measurements over time
with a slope greater than zero [51]. A case–control study
comparing the interdialytic BP profile of 25 patients with
intradialysis hypertension with that of 25 age-match ed and
sex-matched controls with normal intradialytic hemody-
namic response [52] made the important observation that
intradialysis hypertension is a phenomenon superimposed
to background interdialytic hypertension, as patients with
intradialysis hypertension had higher 44-h interdialytic BP
than controls. Of note, patients with intradialysis hyperten-
sion had also a gradual BP decline during the first 24 h after
dialysis, which contrasted with the (typical) gradual
increase from postdialysis onwards in patients without
intradialytic hypertension.
PREVALENCE OF HYPERTENSION IN
THE HEMODIALYSIS POPULATION BY
THE VARIOUS METRICS A N D
DEFINIT IONS
The estimates of the prevalence, treatment and control of
hypertension among patients on chronic dialysis are highly
variable. This variability in large part arises from differences
in the definitions used to diagnose hy pertension and on the
setting of BP measurement (i.e. routine peridialytic BP
recordings or interdialytic ABPM) in the various st udies
[1,53–56].
Office or peridialytic blood pressure recordings
Hypertension is highly prevalent among patients with CKD
who are not yet on dialysis. In a cross-sectional analysis of
10 813 CKD patients participating in the Kidney Early Evalu-
ation Program in United States of America, hypertension
(defined as BP 130/80 mmHg or use of antihypertensive
drugs) was detected in 86.2% of the overall study cohort;
prevalence of hypertension exhibited a stepwise increase
with advancing stage of CKD, increasing to 95.5% (or 91%
with the use of 140/90 threshold) in participants with stages 4
and 5 CKD [57]. A study of patients with predialysis CKD
followed in a low-clearance clinic [mean estimated glomer-
ular filtration rate (eGFR) 14.5 ml/min per 1.73 m
2
] showed
again the prevalence of hypertension to be 95% [58], indi-
cating that almost all CKD patients just before the initiation of
renal replacement therapy are hypertensive.
Initiation of dialysis may have a substantial impact on
management of hypertension, as dialysis represents a
potent thera peutic tool to remove sodium and fluid excess
and improve BP control. Thus, hypertension prevalence in
dialysis patients may appear lower than in those with
predialysis CKD. However, hypertension prevalence after
initiation of dialysis depends on the clinical policies
adopted in each dialysis unit. In some units where long
dialysis and st rict control of salt intake are prescribed,
hypertension has a lower prevalence than in those where
such clinical policies are not applied [59]. However, increas-
ing dialysis time to more than 4 h may be not feasible due to
a number of factors including limited facility and staff
resources, patient preferences and others.
TABLE 1. Diagnosis of hypertension in dialysis patients
Hypertension in dialysis patients should be defined on the basis of home BP
or ABPM measurements. Thresholds and methods proposed by the ASH/
ASN [5], the EURECA-m working group of ERA-EDTA [11] and the
relevant ESH Guidelines [24,41,44] can be used as follows:
Home BP in hemodialysis: An average BP 135/85 mmHg for
measurements collected in the morning and in the evening over 6
nondialysis days (covering a period of 2 weeks). Measures should be
performed in a quiet room, with the patient in seated position, back
and arm supported, after 5 min of rest, and with two measurements
per occasion taken 1–2 min apart
Home BP in peritoneal dialysis: an average BP 135/85 mmHg over 7
consecutive days with measurements collected as above
ABPM in hemodialysis: an average BP 130/80 mmHg over 24-h
monitoring during a mid-week day free of hemodialysis. Whenever
feasible ABPM should be extended to 44-h, that is covering a whole
mid-week dialysis interval
ABPM in peritoneal dialysis: an average BP 130/80 mmHg over 24-h
monitoring
For hemodialysis patients no recommendation can be made on the basis
of predialysis or postdialysis BP. When neither ABPM nor home BP
measurements are available in these patients, the diagnosis can be
made on the basis of office BP measurements taken in a mid-week
day free of hemodialysis, that is the average of three measurements
with 1–2 min interval obtained in the sitting position by trained
personnel after at least 5 min of quiet rest. The threshold of office
BP 140/90 mmHg recommended by current guidelines for th e
definition of hypertension in CKD patients can be used for
hemodialysis patients
For peritoneal dialysis patients office BP 140/90 mmHg obtained as
described immediately above can be used for the diagnosis of
hypertension
BP, blood pressure; ABPM, ambulatory blood pressure monitoring; ASH, American Society
of Hypertension; ASN, American Society of Nephrology; EURECA-m, European Renal and
Cardiovascular Medicine working group; ERA-EDTA, European Renal Association-
European Dialysis and Transplant Association; ESH, European Society of Hypertension.
Sarafidis et al.
660 www.jhypertension.com
Volume 35 Number 4 April 2017
Copyright © 2017 Wolters Kluwer Health, Inc. All rights reserved.
In epidemiology studies in hemodialysis patients in the
United States that used different ways to define hyperten-
sion, the prevalence of hypertension ranged between 72
and 88% of the total population studied (Table 2). Despite
the high proportion of hypertensive patients using antihy-
pertensive medications, the amount of those that had their
BP under control was low in the majority of these studies,
that is roughly between 30 and 50% [1,55,60]. Information
on hypertension prevalence in dialysis patients in countries
other than the United States of America is limited. In studies
made within the frame of the Dialysis Outcomes and
Practice Patterns Study (DOPPS), the prevalence of hyper-
tension was very high and rising ov er time in all countries.
In the last of these surveys (2011), hypertension prevalence
ranged from 78% in Japan to 96% in Germany [61].
Interdialytic ambulatory blood pressure
monitoring
When estimated by the ‘gold standard’ method of 44-h
interdialytic ABPM and defining hypertension as average
SBP at least 135 mmHg and/or DBP at least 85 mmHg or use
of antihypertensive medications the prevalence of hyper-
tension was 82% in a population of 369 predomi nantly
African-American patients who received hemodialysis treat-
ment in units affiliated with an American university [56].
Eighty-nine percent of hypertensive patients were treated
with antihypertensive drugs, but the rate of 44-h BP control
(i.e. patients with average BP below the above thresholds)
was as low as 38% [56]. Poor hypertension control in this
study was associated with a higher number of antihyper-
tensive drugs and fluid overload as measured by the inferior
vena cava diameter in expiration [62]. Apart from this study
in African Amer icans, no large surveys reporting hyperten-
sion prevalence in dialysis patients based on ABPM have
been performed in other ethnicities and in other countries
to date.
BLOOD PRESSURE AND THE RISK FOR
CARDIOVASCULAR EVENTS AND DEATH
IN HEMODIALYSIS PATIENTS
The relationship of BP with all-cause and cause-specific
mortality in hemodialysis patients is a controversial issue.
Several studies have shown that in the BP range (e.g. SBP
110–180 mmHg) in which the event risk increases
substantially with BP increase in the general population,
there is either no relationship or a U-shaped association of
pre or postdialysis SBP and DBP with all-cause and car-
diovascular mortality [63–66] a phenomenon described as
‘reverse epidemiology of hypertension’ in the dialysis
population. Some studies suggested that low BP in hemo-
dialysis is associated with early mortality and deaths of
primarily noncardiac origin, indicating poor physiological
reserve and frailty due to comorbid conditions (i.e. terminal
cancer, congestive heart failure) to be the underlying fac-
tors of mortality [67]. However, this flat or U-shaped associ-
ation raised substantial concerns on whether BP-lowering
as a whole is a strategy associated with benefits for these
patients [68]. More recent observations support that this
phenomenon is rather due to the inadequacy of peridialytic
BP recordings per se to describe the true BP load, than to a
true flat or U-shaped relationship of BP with cardiovascular
morbidity and mortality. Of note, a study of more than
44 000 hemodialysis patients in the United States suggested
postdialysis pulse pressure (PP) to be associated with
higher risk of mortality (12% higher risk for every 10 mmHg
increase in PP), whereas postdialysis SBP displayed an
inverse relationships with risk [69]. In another cohort of
11 142 hemodialysis patients, high postdialysis SBP and low
predialysis and postdialysis DBP were associated with
mortality, implicating again high PP to be a causal factor
[70]. Further to that, a recent analysis in 24 525 patients from
the DOPP S study indicated that the U-shape between BP
and mortality was mostly observed for SBP (predialysis
SBP < 130 mmHg or at least 160 mmHg was associated with
higher mortality), but not for DBP, where a higher mortality
rate was only observed in patients with predialysis DBP less
than 60 mmHg, suggesting that increased PP/arterial stiff-
ness and/or comorbid conditions ma y be responsible for
these associations [71].
In contrast to the unclear association of peridialytic BP
recordings with all-cause and cardiovascular mortality,
prospective cohort studies have shown that interdialytic
BP recorded either by home or ABPM associates mor e
clearly with mortality and cardiovascular event s as it is
documented in the general population. In a group of 57
treated hypertensive hemodialysis patients prospectively
followed for a mean period of 34.4 20.4 months, Amar
et al. [4] showed elevated 24-h ambulatory PP [relative risk
(RR): 1.85 for each 10 mmHg increase in PP; 95%
TABLE 2. Prevalence, treatment and control of hypertension in hemodialysis patients
Reference Year N Definition of hypertension
Prevalence of
hypertension
(%)
BP treatment
among
hypertensive
patients (%)
BP control
among
hypertensive
patients (%)
Salem [55] 1995 649 Prehemodialysis MAP 114 mmHg or use of
antihypertensive agents
71.9 81.5 48.6
Rahman et al. [60] 1999 489 Prehemodialysis SBP 140 mmHg and/or
DBP 90 mm
87.7 93.2 71.1
Agarwal et al. [1] 2003 2535 1-week average prehemodialysis
SBP > 150 mmHg and/or DBP > 85 mmHg,
or use of antihypertensive agents
85.8 88.4 30.3
Agarwal [56] 2011 369 44-h interdialytic ambulatory
SBP 135 mmHg and/or DBP 85 mmHg or
use of antihypertensive medications
82 89 38
MAP, mean arterial pressure.
Hypertension in dialysis patients
Journal of Hypertension www.jhypertension.com 661
![FIGURE 1 Hazard ratios for all-cause mortality for quartiles of predialysis, postdialysis, home and ambulatory SBP. Higher levels of home blood pressure and ambulatory blood pressure were significantly associated with mortality, whereas predialysis and postdialysis blood pressure was not. P values are those reported for linear trend. HD, hemodialysis; and Q, quartile. Reproduced with permission [3].](/figures/figure-1-hazard-ratios-for-all-cause-mortality-for-quartiles-2bgd9xl4.webp)
![FIGURE 3 Weekly average intradialytic SBP during hemodialysis with low and high dialysate sodium by randomization sequence (Group 1: low-then-high dialysate Na) and (Group 2: high-then-low dialysate Na); P<0.001 by adjusted mixed linear regression. Reprinted with permission [50].](/figures/figure-3-weekly-average-intradialytic-sbp-during-2n9f8trx.webp)
![FIGURE 2 Changes in aortic blood pressures, wave reflections and arterial stiffness parameters between the first and the second interdialytic day D[Day(2) Day(1)], in comparison with relevant changes between the second and the third interdialytic day D[Day(3) Day(2)]. AoSBP, aortic systolic blood pressure; AoDBP, aortic diastolic blood pressure; AoPP, aortic pulse pressure; AIx, augmentation index; AIx(75), heart rate-adjusted AIx; PWV, pulse wave velocity. Reprinted with permission [87].](/figures/figure-2-changes-in-aortic-blood-pressures-wave-reflections-3757q5sz.webp)
![FIGURE 4 Blood pressure measured by 44-h ambulatory blood pressure monitoring over the interdialytic period (a) and self-measured by the patients at home (b) in the Hypertension in Hemodialysis Patients Treated with Atenolol or Lisinopril trial. Dotted lines: lisinopril group, solid lines: atenolol group. Reprinted with permission [188].](/figures/figure-4-blood-pressure-measured-by-44-h-ambulatory-blood-1wttmdjr.webp)