WILDCARD

The Prevalence of Symptoms in End-Stage

Renal Disease: A Systematic Review
Fliss E.M. Murtagh, Julia Addington-Hall, and Irene J. Higginson
Symptoms in end-stage renal disease (ESRD) are underrecognized. Prevalence studies have focused
on single symptoms rather than on the whole range of symptoms experienced. This systematic
review aimed to describe prevalence of all symptoms, to better understand total symptom burden.
Extensive database, “gray literature,” and hand searches were undertaken, by predefined protocol,
for studies reporting symptom prevalence in ESRD populations on dialysis, discontinuing dialysis, or
without dialysis. Prevalence data were extracted, study quality assessed by use of established criteria,
and studies contrasted/combined to show weighted mean prevalence and range. Fifty-nine studies in
dialysis patients, one in patients discontinuing dialysis, and none in patients without dialysis met the
inclusion criteria. For the following symptoms, weighted mean prevalence (and range) were fatigue/
tiredness 71% (12% to 97%), pruritus 55% (10% to 77%), constipation 53% (8% to 57%), anorexia 49%
(25% to 61%), pain 47% (8% to 82%), sleep disturbance 44% (20% to 83%), anxiety 38% (12% to 52%),
dyspnea 35% (11% to 55%), nausea 33% (15% to 48%), restless legs 30% (8%to 52%), and depression
27% (5%to 58%). Prevalence variations related to differences in symptom definition, period of
prevalence, and level of severity reported. ESRD patients on dialysis experience multiple symptoms,
with pain, fatigue, pruritus, and constipation in more than 1 in 2 patients. In patients discontinuing
dialysis, evidence is more limited, but it suggests they too have significant symptom burden. No
evidence is available on symptom prevalence in ESRD patients managed conservatively (without
dialysis). The need for greater recognition of and research into symptom prevalence and causes, and
interventions to alleviate them, is urgent.
© 2007 by the National Kidney Foundation, Inc.
Index Words : End-stage renal disease; Symptoms; Symptom prevalence; Systematic review; Dialysis

T he incidence of advanced chronic renal

failure is 148 per million per year in the
United Kingdom (UK), with an age-related
incidence of 588 per million per year in those
80 years of age and older.1 The numbers of
older patients with end-stage renal disease
(ESRD) is rising rapidly. In 1997, 16% of adult
patients starting renal replacement therapy
(RRT) in the UK were 65 years of age or older,
with 1% 75 years of age or older. By 2002, the
percentages had increased to 24% in patients
65 years of age or older, and 3% in patients 75
years or older.2 This increase in the numbers
of older people starting RRT has been noted in
Canada3 and the United States (US),4and pre-
dictive models suggest this rise in elderly
From the Department of Palliative Care and Policy, Kings
College London, London, UK; and School of Nursing and
Midwifery, University of Southampton, Southampton, UK.
The work was funded by Guy’s and St. Thomas’ Charity.
Address correspondence to Fliss Murtagh, MRCGP, MSc,
Department of Palliative Care and Policy, Weston Education
Centre, Cutcombe Rd, London, SE5 9RJ, UK. E-mail: fliss1@
doctors.org.uk
© 2007 by the National Kidney Foundation, Inc.
1548-5595/07/1401-0013$32.00/0
doi:10.1053/j.ackd.2006.10.001
ESRD patients will continue for some years to
come.5
As the numbers of older people with ESRD
rise, debate grows over outcomes and the
value of dialysis.6 Several studies have ex-
plored the relevance of age, comorbidity, and
functional status to survival and disease bur-
den on dialysis,7–9 and one UK study has
evaluated survival in those choosing not to
dialyse. This study concluded that, in high-
risk dependent patients, the decision to dial-
yse had little impact on survival.10 Although
age alone clearly should not be a barrier to
dialysis, an understanding of survival predic-
tors and disease burden (both with and with-
out dialysis) is critical to this debate.
Symptoms are a key contributor to over-
all disease burden, and patients identify
good symptom management as very high
priority.11,12 The extent of symptom burden
is often unrecognized in ESRD, particularly
in those dying of the disease.13–15 This sys-
tematic review was, therefore, undertaken
to determine the prevalence of symptoms in
ESRD, with special consideration of the end-
of-life period, and the whole range of symp-
toms experienced.

82 Advances in Chronic Kidney Disease, Vol 14, No 1 (January), 2007: pp 82-99

 Symptoms in End-Stage Renal Disease
Methods
Review Questions
This systematic review aimed to identify the
prevalence of symptoms in patients with
ESRD on dialysis, the prevalence of symptoms
in patients with ESRD who are managed con-
servatively (without dialysis), and the preva-
lence of symptoms in patients with ESRD who
are discontinuing dialysis.
Literature Identification
The following databases were searched for
studies in English that reported the epidemi-
ology of symptoms in ESRD patients: British
Nursing Index (1985 to April 2005), CINAHL
(1982 to April Week 4, 2005), EBM Reviews
(Cochrane DSR, ACP Journal Club, DARE,
and CCTR to 1st quarter 2005), Embase (1980
to Week 15, 2005), Medline (1966 to March
Week 5, 2005), and PsychInfo (1967 to April
Week 1, 2005). Individual searches were car-
ried out for the main author of included stud-
ies, and reference lists of included articles
were also searched. Citation searches were
also undertaken of included studies by use of
Science Citation Index Expanded. Zetoc,
BioMed Central Meetings Abstracts, and
Medscape Conference databases and the Web
sites of national/international renal organiza-
tions were also searched. The following search
terms were used:
Kidney failure, chronic, renal replacement
therapy NOT kidney transplant, “not for
dialysis.”
Symptom$, pain, dyspnea, pruritus, nausea,
vomiting, anorexia, constipation, diarrhea,
fatigue/tiredness, depression, anxiety.
Epidemiology, incidence, prevalence.
Extensive preliminary searching informed se-
lection of terms.
Inclusion/Exclusion Criteria
Inclusion/exclusion criteria were defined ac-
cording to three components: study design,
study populations (including renal-manage-
ment pathway), and settings. Interventions
and outcomes (usual additional components
for defining inclusion/exclusion criteria in re-
83
views) were not used, because the review
questions relate solely to descriptive data on
symptom prevalence. “Renal-management
pathway” refers to whether the ESRD was
being managed with hemodialysis (HD), with
peritoneal dialysis (PD), with kidney trans-
plantation, with no renal replacement therapy
(RRT) at all (conservatively managed), or with
discontinuation of dialysis. The inclusion cri-
teria were, thus, defined as follows:
1. Study populations of adult patients with a
principal diagnosis of end-stage renal dis-
ease. Treatment modalities of hemodialy-
sis, peritoneal dialysis, or conservative
management were included, as were stud-
ies of patients discontinuing dialysis.
Studies of renal-transplant patients alone
were excluded, although mixed study
populations, of transplant and dialysis pa-
tients, were included.
2. Studies collecting data on symptom inci-
dence or prevalence, where these data are
reported separately (not as part of a qual-
ity of life or other summative score).
3. Studies of any design were included pro-
vided that the study population was to
some extent representative of the denom-
inator population (“denominator popula-
tion” defined below). This criterion ex-
cluded case series or case reports.
4. Any setting (hospital, community, day
care, out-patient, or nursing home).
Data Extraction
Data were extracted from each included study
by use of a standardized predesigned form to
collate study details and findings on key qual-
ity criteria. Quality criteria were cross-
checked in a random sample of the selected
papers by an independent reviewer.
Analysis of Results
Data from included studies were compared
and combined, giving range of prevalence
and, where possible, weighted mean preva-
lence (weighted by size of study).
84 Murtagh, Addington-Hall, and Higginson
Results
General Findings
The search strategy identified 11,695 papers
overall. Reasons for exclusion of studies are
not given, in view of the large numbers. Com-
mon reasons for exclusion were the following:
symptoms reported but no incidence or prev-
alence data collected;
only summary symptom data presented (the
symptom component of a quality of life
measure or a total symptom score, rather
than prevalence data for each individual
symptom);
case series or single case report only.
Sixty-four papers, relating to 61 different
studies, fulfilled the selection criteria.
Quality of the Included Studies
All included studies were service- rather than
population-based. The main purpose of the
studies was either to measure symptom prev-
alence, to measure symptom prevalence to
correlate it with other measures (such as clin-
ical, psychological, or functional status or ill-
ness intrusiveness), or to measure quality of
life. Numerous studies of quality of life in
ESRD were identified by the search strategy,
and many of these studies collected data on
symptoms, but only a few16 –18 reported the
details of individual symptom prevalence
and, thus, fulfilled the inclusion criteria.
The study populations were well described
in terms of age, sex, underlying renal pathol-
ogy, and renal-management pathway, but
only five studies described their study popu-
lation in terms of disease severity.19 –23 The
denominator population (defined as the “pop-
ulation at risk”— ie, the whole population
from which the study population was drawn)
was not always defined or described, al-
though seven studies 24 –30 recruited all eligi-
ble participants (so study and denominator
populations were identical). Seven studies
chose to overcome selection bias by randomly
selecting participants, 31–37 and five studies
compared their study population with refer-
ence populations from Renal Registry data,
rather than their denominator popula-
tion.19,38 – 41 Inclusion and exclusion criteria
were usually well defined, but response rate
was not always quoted and varied in defini-
tion, with some studies including and others
excluding those who declined to participate.
All the studies were prospective, except
for two; one use retrospective data,19 and
the second (of patients discontinuing dialy-
sis) collected some data (on day before
death) retrospectively.13,42 All studies but
one relied on patient-reported data; the one
exception was the same study of patients
discontinuing dialysis,13,42 in which the data
were largely derived from proxies (families
or staff). Apart from this study,13,42 longitu-
dinal data on symptom prevalence were not
reported. Two studies collected symptom
data from the same patients on more than
one occasion, 33,43 but the data were not
reported so as to allow evaluation of change
in symptoms over time.
A variety of symptom-assessment tools
were used, some (eg, the Beck Depression
Inventory) previously well validated and oth-
ers not previously validated. The symptom-
assessment tools used varied from those in-
tended as a screening tool to those adopting
full diagnostic criteria. Considerable variation
also occurred in the time period over which
prevalence was measured, and this variation
was sometimes neither stated nor evident.
Footnotes to the tables of prevalence data clar-
ify the time period to which prevalence data
relates and definition of the symptom, where
available. Variation in tools and in period of
prevalence resulted in wide differences in re-
ported prevalence. An example of this feature
is depression, in which the prevalence of the
patient “feeling sad or depressed” is high
(26% feeling sad at some time over previous
week,14 and 55% feeling sad at some time over
previous 4 weeks44), whereas depression
(identified by a Hospital Anxiety and Depres-
sion Scale score ⬎11) is lower at 11%.36
Both frequency and severity of a symptom
included in the definition altered apparent
prevalence. An example is anorexia, which is
reported as 53% in one study44 but between
8% and 34% in another study,23 depending on
whether it was defined as “occurring occa-
sionally” or “occurring daily.” The use of dif-
ferent symptom definitions, levels of severity,
 Symptoms in End-Stage Renal Disease
Figure 1. Weighted mean prevalence of symptoms (%) in ESRD (weighted by size of study).
and period of prevalence often suggested how
the wide apparent variations might have
arisen.
The Range of Symptoms Identified
Most studies sought only one symptom, or
just two or three related symptoms, such as
anxiety/depression or sleep disturbance/rest-
less legs. Only 11 studies looked at the full
range of symptoms experienced by ESRD pa-
tients.14,16,17,19,23,29,36,38,43,45– 47 Curtin et al 38
and Parfrey and colleagues 46,47 each used
patient interviews with over 100 patients to
identify the most common symptoms experi-
enced, and then used these data to inform a
detailed symptom survey. The most common
symptoms identified by Curtin et al38 were
lack of energy, tiredness, dry mouth or thirst,
pruritus, numbness and sleep disturbance,
and those identified by Parfrey et al46,47 were
tiredness, cramps, pruritus, dyspnea, head-
aches, joint pains, and sleep disturbance. Sev-
eral studies of multiple symptoms17,29,36,43,46,47
used the same symptom-assessment instrument
(Parfrey’s Health Questionnaire). Other tools
seeking a full range of symptoms included the
McGill Quality of Life questionnaire,16 the Me-
morial Symptom Assessment Scale (Short
Form),14 a symptom questionnaire devised for
the particular study,21,44 and nephrologist re-
port or interview.19,23 The first two of these are
validated in palliative cancer populations but
not in ESRD populations, whereas both the
Figure 2. Number of included studies reporting each symptom.
85
symptom questionnaire and nephrologist re-
port/interview have not been shown to be valid
or reliable. Crucially, Parfrey’s Health Question-
naire, the McGill Quality of Life questionnaire,
and the Memorial Symptom Assessment Scale
all have free fields that allow scope for the
patient to identify for themselves what addi-
tional symptoms trouble them. Three studies,
the survey by Curtis and colleagues,19 the NE-
COSAD study,21 and the study by Virga and
colleagues,23 did not use free fields; rather they
defined in advance the specific symptoms to be
sought.
Prevalence of Individual Symptoms
Figure 1 depicts the weighted mean preva-
lence for each symptom, and Figure 2 depicts
the number of studies that report each symp-
tom.
Anxiety and Depression
Fifteen studies were identified describing
prevalence of depression or anxi-
ety,20,22,26,32,34,35,37,41,48 –54 and three further
studies reported anxiety and depression prev-
alence as part of a survey of multiple symp-
toms.14,36,38 Only six studies explored anxiety
prevalence.14,20,26,36,38,50 The findings are illus-
trated in Table 1. Range of prevalence was
12% to 52% for anxiety and 5% to 58% for
depression. Weighted mean prevalence of
anxiety and depression were 38% and 27%,
respectively.
86 Murtagh, Addington-Hall, and Higginson

Table 1. Reported Prevalence of Anxiety and Depression in ESRD

Prevalence of Anxiety % Prevalence of depression % (Definition Period of
Study Population (Definition Used) Used) Prevalence

al Hihi et al 2003 53 HD patients 58 (Beck Depression Inventory Previous 7

score ⬎ 10) days
Craven et al 1988 99 dialysis 45 (Beck Depression Inventory Point
patients score ⬎ 9) prevalence
12 (DSM-III criteria) Point
prevalence
Curtin et al 2002 307 HD patients 52 (Patient report of 55 (Patient report of feeling sad or Previous 4
feeling anxious or depressed) weeks
worried)
Farmer et al 1979 32 HD patients 12 (“Anxiety neurosis” 12 (“Depression or depressive Previous
on standardized neurosis” on standardized week
interview) interview)
Hinrichsen et al 1989 124 HD patients 18 (Research Diagnostic Criteria for Not defined
minor depression)
7 (Research Diagnostic Criteria for
major depression)
Hong et al 1987 60 ESRD 5 (DSM-III criteria for major Previous 2
patients depression) weeks
Kutner et al 1985 128 HD and PD 12 (Scored in anxiety 27 (Scored in depression range of Not defined
patients range of Zung self- Zung self-rating depression
rating depression score)
score)
Lopes et al 2002 5,256 HD 21 (Patient report in response to 2 Over
patients questions on mood from previous
KDQOL-SF) relating to past 4 4 weeks
weeks)
17 (Physician diagnosed from
medical records)
Martin and 72 PD patients 39 (Score ⬎ 8 on 23 (Score ⬎ 8 on depression Point
Thompson 2000 anxiety component component of Hospital Anxiety prevalence
of Hospital Anxiety and Depression scale)
and Depression
scale)
McCann and Boore 39 HD patients 32 (Score on anxiety 11 (Score on depression component Previous
2000 component of of Hospital Anxiety and week
Hospital Anxiety Depression Scale ⬎ 11)
and Depression
Scale ⬎ 11)
O’Donnell and 35 HD patients 26 (DSM-III-R criteria, substituting Previous 7
Chung 1997 specific physical symptoms with days
psychological symptoms. Same
% identified by Beck Depression
Inventory score ⬎ 9, including
all physical symptoms)
6 (DSM-III-R criteria, excluding
physical symptoms caused by
the medical condition)
14 (Beck Depression Inventory
score ⬎ 15)
34 (DSM-III-R criteria, including all
physical symptoms whatever the
etiology)
 Symptoms in End-Stage Renal Disease 87

Table 1. Reported Prevalence of Anxiety and Depression in ESRD (Cont’d)

Prevalence of Anxiety % Prevalence of depression % Period of
Study Population (Definition Used) (Definition Used) Prevalence

Rodin and Voshart 115 dialysis 26 (Beck Depression Inventory Previous 7

1987 patients score ⬎ 15) days
awaiting renal
transplant
Smith et al 1985 60 HD or 5 (DSM-III criteria) Point
posttransplant prevalence
patients
47 (Beck Depression Inventory;
score cutoff not defined)
Walters et al 2002 422 patients 45 (Defined as positive on Not defined
starting HD screening measure of 3 items
derived from Diagnostic
Interview Schedule)
Watnick et al 2003 23 patients 44 (Beck Depression Inventory Previous 7
starting HD score ⬎14) days
or PD
Weisbord et al 2003 19 HD patients 26 (Defined as feeling 26 (Defined as feeling sad) Previous 7
with high nervous) days
comorbidity
Wuerth et al 2001 136 PD patients 49 (Beck Depression Inventory Previous 7
score ⬎10) days
Wuerth et al 2005 380 dialysis 49 (Beck Depression Inventory Previous 7
patients score ⬎10) days
Range 12–52 5–58
Weighted mean 38 27
prevalence

Abbreviations: DSM-III-R, Diagnostic and Statistical Manual of Mental Disorders, Third Edition, Revised; ESRD, end-stage
renal disease; HD ⫽ hemodialysis; KDQOL-SF, Kidney Disease Quality of Life - Short Form; PD, peritoneal dialysis.

Eight studies used the Beck Depression In-
ventory screening tool to screen for depres-
sion, although not all studies used the stan-
dard cutoff of greater than 10. Other studies
use standardized psychiatric interview or
other validated screening tools, such as the
Hospital Anxiety and Depression scale,20 or
the Zung self-rating depression scale.50 Con-
siderable debate is taking place about diagno-
sis of depression in this medically ill popula-
tion because many of the neurovegetative
symptoms of depression overlap with the
physical symptoms of illness. O’Donnell and
Chung 22 are helpful in clarifying this debate
by comparing exclusive (where criteria based
on physical symptoms are excluded from the
diagnostic criteria), substitutive (where alter-
native criteria are substituted for criteria
based on physical symptoms). and inclusive
(where criteria based on physical symptoms
are included in the diagnostic criteria) ap-
proaches. They concluded that the inclusive
and substitutive approaches are more consis-
tent with previous prevalence reports,
whereas an exclusive approach is likely to
underdiagnosis depression.
Pain
Four studies were identified that described
pain prevalence14 –16,23 (see Table 2). The
study by Davison15 concentrated on pain
prevalence alone, and the remaining three
studies14,16,23 concentrated on multiple symp-
toms. The range of pain prevalence reported
was from 8% to 82%, with varying definitions,
methods of identifying prevalence, and sever-
ity included in the definition. The weighted
mean prevalence of pain was 47%.
Davison15 used both the Brief Pain Inven-
tory55 and the McGill Pain Questionnaire,56
whereas the other studies used the McGill
Quality of Life Questionnaire,16 an unvali-
dated symptom questionnaire at interview,23
or the Memorial Symptom Assessment Scale–
88 Murtagh, Addington-Hall, and Higginson
Table 2. Reported Prevalence of Pain in ESRD
Study Population
Davison 2003 205 HD patients
Kimmel et al 2003 165 HD patients
Virga et al 1998 73 HD patients
Weisbord et al 2004 19 HD patients with
high comorbidity
Range
Weighted mean
prevalence
Short Form.14A few studies reported specific
kinds of pain, particularly muscle cramps33
and headaches,31,33 which are frequently de-
scribed in dialysis populations. Remaining
studies either did not ask about pain,21 or
restricted their survey to specific pains known
to occur in ESRD,44,46,47 such as headaches,
joint pain, or muscle cramps. Parfrey’s Health
Questionnaire46,47 is one example of a symp-
tom-assessment tool that seeks data only on
very specific pains (headache, joint pain, an-
gina, and cramps), and because several of the
studies of multiple symptoms adopted
Parfrey’s Health Questionnaire, this limitation
has been perpetuated.
Pruritus
Seventeen studies that reported itching or pruritus
were identified,14,17,19,21,23,24,28,29,36,38,43,46,47,57–62
and their findings are detailed in Table 3.
Weighted mean prevalence was 55%. Re-
ported prevalence varied considerably, with a
range from 10% to 77%, but the higher figures
were from studies in which the symptom def-
inition and the severity included were not
clearly defined21,58 and a third study62 that
included mild (as well as moderate and se-
vere) pruritus together in the prevalence data.
Greater consistency was seen across the re-
maining studies, with their reported preva-
lence more consistently around 50% to 60%.
Restless Legs Syndrome
Eleven studies reported the prevalence of rest-
less legs19,23,25,38,39,60,62– 66 (see Table 4).
Prevalence of Pain %
(Definition Used) Period of Prevalence
55 (Moderate or severe on Brief Current
Pain Inventory)
82 (Moderate or severe on Brief Over previous 24 hours
Pain Inventory)
49 Over previous 2 days
19 (Occurs occasionally) Not defined
8 (Occurs daily)
53 (Patient report on Memorial Over previous week
Symptom Assessment
Scale - Short Form)
8–82
47
The range was 8% to 52%, and weighted-
mean prevalence was 30%. Again, prevalence
varied considerably, but much of this variabil-
ity can be attributed to the narrowness or
breadth of the definition, plus variations in
the time period over which prevalence is re-
corded. A narrow definition, such as “restless
legs occurring at least daily,”23 gave rise to
prevalence of 8%, whereas a much broader
definition (patients answered “yes” to
whether they had ever had “a disagreeable
feeling in the legs, with aching, creeping, and
motor restlessness, with an urge to move the
legs”) gave rise to prevalence data of 50%. The
level of severity included in the definition also
affects reported prevalence, with the inclusion
of “mild” restless legs syndrome giving the
relatively high prevalence of 46%.67 Recent
studies have used the more rigorous criteria
developed by the International Restless Legs
Syndrome Study Group68 for identifying
prevalence.
Sleep Disturbance
Sleep disturbance is reported as a common
problem in ESRD patients, but surveys of
prevalence are again beset by the challenge of
definition. Eleven papers were identified that
focus solely on the prevalence of sleep distur-
bance,18,30,60,65,69 –75 and six further studies in-
cluded sleep disturbance in their survey of
multiple symptoms.16,23,29,36,43,46 Considerable
variation in definition of sleep disturbance
was seen, as well as varying time periods over
 Symptoms in End-Stage Renal Disease 89

Table 3. Reported Prevalence of Pruritus in ESRD

Prevalence of Pruritus or Itching
Study Population % (Definition Used) Period of Prevalence

Balaskas et al 1993 76 HD patients 54 At time of interview

28 Before dialysis started
Balaskas et al 1993 113 PD patients 62 At time of interview
30 Before dialysis started
Balaskas et al 1998 54 HD patients 54 (Replied “yes” to the Point prevalence
question “Is itching a
problem for you now?”)
Balaskas et al 1998 43 PD patients 49 (Replied “yes” to the Point prevalence
question “Is itching a
problem for you now?”)
Barrett et al 1990 147 HD patients 54 Not defined
Barrett et al 1990 44 PD patients 52 Not defined
Curtin et al 2002 307 HD patients 73 (Patient report of itchy skin) Previous 4 weeks
Curtis et al 2002 238 patients starting 38 Not defined
dialysis
Frank et al 2003 71 predialytic, HD 60 (Refers to PD patients) Current symptom
and PD patients
48 (Refers to HD patients)
Hui et al 2000 201 PD patients 71 (Includes mild, moderate, Not defined
and severe pruritus; precise
definition not described)
Masi and Cohen 1992 81 HD patients 51 (Itch scored by patient as ⬎ Over previous month
3 on visual analogue scale of
0–10)
Masi and Cohen 1992 34 PD patients 59 (Itch scored by patient as ⬎ Over previous month
3 on visual analogue scale of
0–10)
McCann and Boore 39 HD patients 28 (All grades of severity) Not defined
2000
7 (Severe or very severe)
Merkus et al 1999 106 PD patients 68 Previous three weeks
Merkus et al 1999 120 HD patients 73 Previous three weeks
Parfrey et al 1987 107 dialysis patients 54 (All grades of severity) Not defined
11 (Severe or very severe)
Parfrey et al 1988, 1989 97 dialysis patients 49 (All grades of severity) Over previous few
weeks
10 (Severe or very severe)
Subach and Marx 2002 74 HD patients 70 (Experienced itching, but Not defined
definition, severity or time
period not defined)
Szepietowski et al 2002 130 HD patients 41 Current symptom
77 At any time during
renal disease period
Virga et al 1998 73 HD patients 57 (Occurs occasionally) Not defined
10 (Occurs daily)
Weisbord et al 2003 19 HD patients with 53 Over previous week
high comorbidity
Winkelman et al 1996 204 HD patients 36 (Patients answered “a lot” or Not defined
“horrible” to whether they
had itching sensations
anywhere on body)
90 Murtagh, Addington-Hall, and Higginson

Table 3. Reported Prevalence of Pruritus in ESRD (Cont’d)

Prevalence of Pruritus or Itching
Study Population % (Definition Used) Period of Prevalence

Zucker et al 219 HD 48 (At least 3 episodes of itch during a See definition in

2003 patients period of 2 weeks or less, or regular previous column
itch during a period of 6 months but
less frequently)
40 (At least 3 episodes of itch during a At some time in the past
period of 2 weeks or less, or regular
itch during a period of 6 months but
less frequently)
Range 10–77
Weighted mean 55
prevalence

Table 4. Reported Prevalence of Restless Legs in ESRD

Prevalence of Restless Legs % (Definition Period of
Study Population Used) Prevalence

Cirignotta et al 2002 114 PD patients 33 (Clinical diagnosis of RLS by Current

neurologist) symptoms
50 (Patients answered “yes” to whether
they had ever had “a disagreeable
feeling in the legs, with aching,
creeping, and motor restlessness and
an urge to move the legs”)
Collado-Seidel et al 136 HD patients 23 (Clinical diagnosis of RLS by Not defined
1998 neurologist; a further 9% diagnosed
with “questionable” RLS)
Curtin et al 2002 307 HD patients 52 (Patient report of restless or jumpy Over previous
legs) 4 weeks
Curtis et al 2002 238 patients 24 Not defined
starting dialysis
Gigli et al 2004 601 dialysis 22 (Positive responses to all 4 questions Current
patients proposed by the International Restless symptoms
Legs Syndrome Study Group)
Hui et al 2000 201 PD patients 40 (Moderate or severe RLS) Not defined
Mucsi et al 2005 333 dialysis 14 (Restless Legs Syndrome Current
patients Questionnaire criteria) symptoms
Siddiqui et al 2004 277 HD patients 46 (Mild, moderate, and severe, on Not defined
International Restless Legs Syndrome
Study Group criteria)
Unruh et al 2004 894 HD and PD 32 (“Moderately,” “very,” or “extremely” Over previous
patients bothered by restless legs) 4 weeks
Virga et al 1998 73 HD patients 19 (Occurs occasionally) Not defined
8 (Occurs daily)
Winkelman et al 204 HD patients 23 (Patients answered “a lot” or Not defined
1996 “horrible” to whether they had
“crawling, tingling, or achy sensations
in your arms or legs when you are
resting”)
Range 8–52
Weighted mean 30
prevalence

Abbreviation: RLS, restless legs syndrome.

 Symptoms in End-Stage Renal Disease
which symptoms were sought. The preva-
lence findings are illustrated in Table 5.
Range was 20% to 83% (including all
grades of severity of sleep disturbance, rather
than only severe or very severe). Weighted-
mean prevalence was 44%. The period of
prevalence used varied from point prevalence
up to 3 months, and definitions varied from
simple patient report of a “sleep problem” to
more specific definitions such as “at least one
of the following: problems initiating or main-
taining sleep, early or difficulty waking, tired-
ness on waking, daytime sleepiness.”
Other Symptoms
Prevalence of other symptoms in included
studies are reported in Table 6.14,16,17,19,21,
23,27,29,31,33,36,43,44,46,47,76,77
Symptoms were
rarely defined, and periods of prevalence
again varied considerably, from 2 days to 12
months. Anorexia, constipation, fatigue or
tiredness, nausea, and specific types of pain
(cramps, headache, and joint pains) were
identified as most prevalent. Some of these
data came from a small number of studies,
and the symptom definition, tools, and meth-
ods used have a relatively greater impact. An
example is constipation; only one study aimed
at identifying the prevalence of constipation
in ESRD,76 although constipation was sought
in two further studies of multiple symp-
toms.14,38 The high prevalence reported by
Yasuda and colleagues76 in this study may
partly be a result of the fact that data on
constipation during the previous year were
sought. Three other studies report constipa-
tion prevalence as part of a range of symp-
toms14,27,44 and gave lower reported preva-
lence. These figures vary according to
whether they are based on patient report of
constipation (higher) or on more objective def-
initions (lower).
Symptoms in Patients Managed
Without Dialysis or Discontinuing
Dialysis
Because this review aimed to focus particu-
larly on end-of-life care, symptoms in those
who were discontinuing dialysis or conserva-
tively managed were of particular concern.
91
No studies of conservatively managed ESRD
were identified, but three papers report symp-
tom prevalence in patients discontinuing dial-
ysis, although the three papers relate to the
same study and have been combined for anal-
ysis.13,42,78 These findings are illustrated in
Table 7.
Of the 79 patients followed in this study
from discontinuation of dialysis until death,
only 23 could be meaningfully interviewed,
which illustrates the difficulty of collecting
data from patients themselves as they become
more ill. Nevertheless, by using data collected
from proxies (both staff and families) as well
as that from patients, the authors were able to
describe symptom prevalence in this popula-
tion. Symptom-prevalence data is only re-
ported for the last 24 hours of life, although
mean survival time from last dialysis was 8.2
days.
Discussion
This systematic review clearly demonstrates
that, for patients with ESRD, a wide range of
symptoms are very common, and the overall
symptom burden is high. It also identifies a
glaring lack of evidence on the prevalence of
symptoms in patients withdrawing from, or
being managed without, dialysis. An urgent
need exists for greater recognition within the
field of nephrology of the extent and impact of
symptoms on patients and for systematic re-
search into the incidence and prevalence of
symptoms, their causes, and appropriate in-
terventions to alleviate them. A patient-cen-
tered approach to care demands such recog-
nition because patients themselves give high
priority to recognition, acknowledgment, and
alleviation of symptoms.
As the number of ESRD patients grows,
understanding and managing symptoms ef-
fectively, and, hence, improving quality of life
for those living with ESRD, will become in-
creasingly important. The numbers of patients
starting renal replacement therapy (RRT) for
ESRD are rising steadily, with an annual in-
crease in prevalent RRT patients of 4% in the
UK,2 and a significant increase in the propor-
tion of older patients on RRT has occurred,6
with their associated higher levels of comor-
bidity. Speculating on why symptom preva-
92 Murtagh, Addington-Hall, and Higginson

Table 5. Reported Prevalence of Sleep Disturbance in ESRD

Prevalence of Sleep Disturbance %
Study Population (Definition Used) Period of Prevalence

Barrett et al 1990 147 HD patients 42 Not defined

Barrett et al 1990 44 PD patients 26 Not defined

Devins et al 1993 101 HD, PD & post- 41 (Sleep disturbance defined as Over previous 7 days
transplant patients restless sleep on 3 or more
nights out of 7)

Han et al 2001 82 diabetic HD patients 68 (Defined as one of difficulty Present for at least the
falling asleep, night waking, previous 2 months
early morning waking)

Holley et al 1992 22 PD patients 50 (Defined as trouble sleeping, as Point prevalence

reported by the patient)

Holley et al 1992 48 HD patients 52 (Defined as trouble sleeping, as Point prevalence

reported by the patient)

Iliescu et al 2003 89 HD patients 71 (Poor sleepers defined as global Over previous 1 month
Pittsburgh Sleep Quality Index
score of more than 5)
Kimmel et al 2003 165 HD patients 31 (“Trouble with sleep” as Previous 2 days
identified by patient)

Locking-Cusolito et al 53 HD patients 43 (Difficulty falling asleep on 3 or Over previous 7 days

2001 more nights out of the past 7)

Locking-Cusolito et al 22 PD patients 32 (Difficulty falling asleep on 3 or Over previous 7 days

2001 more nights out of the past 7)

McCann and Boore 39 HD patients 29 (All grades of severity) Not defined

2000 14 (Severe or very severe)

Mucsi et al 2004 78 dialysis patients 49 (“Insomnia,” not otherwise Not defined

defined)

Parfrey et al 1987 107 dialysis patients 35 (All grades of severity) Not defined
8 (Severe or very severe)

Parfrey et al 1988, 97 HD and PD patients 35 (All grades of severity) Over previous few weeks
1989 8 (Severe or very severe)

Sabbatini et al 2002 694 HD patients 45 (Defined as difficulty falling Not defined

asleep and/or night waking,
occurring 7 nights a week for at
least 1 month)

Stepanski et al 1995 81 PD patients 59 (Sleep onset problem) Not defined

73 (Sleep maintenance problem

Venmans et al 1999 16 HD patients 46 (At least one of the following:
problems initiating or
maintaining sleep, early or
difficulty waking, tiredness on
waking, daytime sleepiness)
Tool designed to study
chronic (3-month period)
sleep problems

Virga et al 1998 73 HD patients 37 (Occur occasionally) Not defined

20 (Occur daily)

Walker et al 1995 54 HD patients 83 (Includes disturbed sleep, RLS, Not defined

and daytime sleepiness)

Weisbord et al 2003 19 HD patients with 37 Over previous week

high comorbidity

Winkelman et al 1996 204 HD patients 36 (Patient reported moderate or Not defined

severe sleep problem)

Range 20–83 (Range excludes “severe” or

“very severe”)
Weighted mean 44 (Weighted mean prevalence
prevalence excludes “severe” or
“very severe”)
 Symptoms in End-Stage Renal Disease
lence is so high for these patients is beyond
the scope of this review, but symptoms may
be caused by the renal disease, by comorbid
conditions, by dialysis itself, or by one or
more of these components working together.
Comorbidity may be of particular importance
in patients withdrawing from dialysis or be-
ing managed without dialysis, because it is
likely to be a major factor in selecting this
course of management.
The findings from this systematic review
initially appear to represent wide variation in
the reported prevalence of different symp-
toms. However, on closer analysis, much of
this variation can be attributed to variations in
definition and methodology. First, definition
of the symptoms themselves varies enor-
mously, especially for certain difficult-to-de-
fine symptoms, such as sleep disturbance or
constipation. Second, who defines (and who
reports) a symptom varies. Patient report has
been accepted as the “gold standard” for sub-
jective symptoms such as pain,79,80 although
less so for symptoms such as depression, in
which standardized psychiatric interview is
optimum. Patient report becomes problem-
atic, however, when patients are asked to cat-
egorize their own pain, such as “angina,” in
Parfrey’s Health Questionnaire.47 Third, prev-
alence is often measured over a variable time
period that ranges from point prevalence to
period prevalence up to 1 year. Some symp-
tom questionnaires asked if a symptom had
ever been experienced during the time period,
whereas others asked if a symptom had been
experienced continually during the time pe-
riod, and some did not distinguish these very
different approaches, confusing comparisons
of prevalence between studies further. Fourth,
the tools used to identify symptoms are vari-
able, and evaluation of those tools differs.
Sometimes “screening” tools are used that are
intended to identify a group of patients who
can then be more closely assessed for the
severity of a symptom. Other tools are de-
signed to measure symptom severity and fre-
quency and how much a symptom is distress-
ing to patients, such as the Memorial
Symptom Assessment Scale.81 Some tools
have been well validated, whereas others
have had no real assessment of validity or
reliability. When these considerations are
93
taken into account, explanations for some of
the apparent variation become evident.
More importantly, few attempts have been
made to describe the whole range of symp-
toms in ESRD. Generic symptom tools that
measure a range of symptoms have had lim-
ited use and evaluation in ESRD populations,
which makes comparisons with other popula-
tions challenging. One disease-specific tool,
Parfrey’s Health Questionnaire, has been de-
veloped to cover a wide range of symptoms in
ESRD,47 although some of its limitations are
already described. More recent work has de-
veloped another tool specifically for this pur-
pose, the Dialysis Symptom Index,82 which
attempts to capture the full range of symp-
toms, as well as the degree to which patients
are distressed or bothered by a symptom.
Both The Dialysis Symptom Index and
Parfrey’s Questionnaire use free fields. With-
out free fields, and despite literature review or
expert consensus, a tool cannot be expected to
capture previously unconsidered symptoms.
Relatively few studies were designed spe-
cifically to describe symptom prevalence, and
none were population based. From an epide-
miologic perspective, symptom prevalence
would be more accurately determined on a
population basis, avoiding the bias that arises
both from variations in referrals to different
nephrology services and from the variations
within services that may alter disease progres-
sion and management, and, thus, altering “ap-
parent” symptom prevalence. This feature is
particularly important in ESRD because vari-
ations in ESRD populations and in nephrol-
ogy services between different regions and
countries is well recognized2,83 However,
given the difficulties of undertaking such ep-
idemiologic studies, and the fact that, unsur-
prisingly, none have been identified in this
review, the degree to which the study popu-
lations are representative of the denominator
populations and the generalizability of these
service-based studies must be assessed. In
general, the descriptions of study/denomina-
tor populations and inclusion procedures of-
ten gave insufficient detail to assess whether
study populations were representative or
whether selection bias was likely to be an
important factor. The majority of the studies
reported symptoms in hemodialysis patients;
94 Murtagh, Addington-Hall, and Higginson

Table 6. Reported Prevalence of Other Symptoms in ESRD

Cough
Study Population Abdominal Pain % Anorexia % Constipation % % Cramps %

Antoniazzi et al 2002 123 HD patients

Barrett et al 1990 147 HD patients 53

Barrett et al 1990 44 PD patients 50

Curtin et al 2002 307 HD patients 53 57

Curtis et al 2002 238 patients starting 61 28

dialysis

Devins et al 1990 100 HD, PD and 45

posttransplant
patients

Frank 2003 71 predialytic HD 60

and PD patients >60% but actual
figure not given

Hammer 1998 105 HD patients 28 moderate or severe 8

<3 stools per week

Kimmel 2003 165 HD patients

McCann 2000 39 HD patients 28ⴱⴱ

Merkus 1999 106 PD patients 48 60

Merkus 1999 120 HD patients 25 62

Min 2000 92 PD patients 22

Min 2000 91 HD patients 7

Parfrey et al 1987 107 dialysis patients 11** 44ⴱⴱ

Parfrey et al 1988, 97 dialysis patients 16** 54ⴱⴱ

1989

Virga et al 1998 73 HD patients 34 occasional 29 occasional

Weisbord et al 2003 19 HD patients with 21

high comorbidity

Yasuda et al 2002 268 HD patients 63

Yasuda et al 2002 204 PD patients 59

Range 11–28 25–61 8–57 7–22 28–60⫹

Weighted mean 18 49 53 15 46
prevalence

Abbreviations: DSM-III-R, Diagnostic and Statistical Manual of Mental Disorders, Third Edition, Revised; HD, hemodi-
alysis; KDQOL-SF, Kidney Disease Quality of Life - Short Form; PD, peritoneal dialysis; RLS, restless legs syndrome.
*Excluded from calculation of weighted mean prevalence because only combined nausea and vomiting figures given.
**All grades of severity.

generalization from hemodialysis populations
to conservatively managed or dialysis-with-
drawing ESRD populations is difficult, espe-
cially for those symptoms such as headache,
cough, or muscle cramps, which may, in fact,
be related to the dialysis itself. Symptoms in
the conservatively managed and dialysis-
withdrawing sectors of the ESRD population
have yet to be described (with the single ex-
ception of the work by Cohen and col-
leagues13,42).
Because of the lack of evidence toward the
end of life, specific conclusions about the
symptoms that patients dying with ESRD ex-
perience are difficult to draw, yet understand-
ing this process is becoming increasingly im-
portant. The annual mortality in the ESRD
population, at 24%, is higher than for many
cancers.4 Symptoms (other than those specifi-
cally related to dialysis) in patients either
managed conservatively (without dialysis) or
withdrawing from dialysis are likely more
prevalent in these groups than in those on
dialysis because of worsening disease and
 Symptoms in End-Stage Renal Disease 95

Table 6. Reported Prevalence of Other Symptoms in ESRD

Fatigue or
Dyspnea % Tiredness % Headache % Joint Pain % Nausea % Period of Prevalence

71 At some time during HD

39 72 43 33 Nausea only Not defined

43 68 33 34 Nausea only Not defined

91 patient report 46 48 Nausea only Over previous 4 weeks

76 52 Nausea 34 Vomiting Not defined

45 Over previous 7 days

70 PD
84 HD
97 predialysis

Over previous year

11 12 Over previous 2 days

39** 18** 32** 17 Nausea** Not defined

55 87 38 Nausea only Over previous 3 weeks

51 82 30 Nausea only Over previous 3 weeks

Since start of dialysis

73** 40** 48* Nausea and vomiting** Not defined

77** 39** 39* Nausea and vomiting** Over previous few weeks

38 occasional 15 Nausea, occasional Not defined

42 26 Nausea Over previous week

21 Vomiting

Over past 12 months

Over past 12 months

11–55 12–97 18–71 32–40 15–48

37 71 47 38 33

higher comorbidity. The evidence identified
by this review almost all relates to patients on
dialysis. However, the lack of evidence in
patients managed without dialysis and in
those withdrawing from dialysis is itself an
important negative finding that highlights a
major area for future research. Understanding
how symptoms vary in these two additional
and very different (in terms of prognosis and
trajectory) populations is crucial.
Limited comparisons can be made with
other cancer and noncancer populations to-
ward the end of life. Work by the Symptom
Prevalence Group84 identified symptom prev-
alence in 1,640 cancer patients and reported
pain in 57%, nausea in 21%, dyspnea in 19%,
constipation in 23%, anorexia in 30%, and
insomnia in 9%. A Comparison of these find-
ings with this review suggests that ESRD pa-
tients experience all of these symptoms more
often than do cancer patients. Only pain is
identified in ESRD patients in this review as
96 Murtagh, Addington-Hall, and Higginson
Table 7. Reported Prevalence of Symptoms in 79 Patients Discontinuing Dialysis
Diarrhea Dyspnea
Agitation % % %
Present 30 14 25
Severe 1 1 3 3
Data are from Cohen et al 2000, 2000, 2002.
slightly less common. Other renal-specific
symptoms, such as pruritus and restless legs,
not reported by the Symptom Prevalence
Group, add to the symptom burden experi-
enced by ESRD patients. A comparison of
symptom prevalence in cancer and other non-
cancer conditions, including kidney disease,
found similar or higher levels of most symp-
toms in kidney disease, with the exception of
pain that was slight less common than in can-
cer.85 A further systematic review of pallia-
tive-care need by Franks and colleagues86 re-
ports prevalence ranges of symptoms in both
cancer and noncancer populations again com-
parable to those identified in ESRD patients in
this review.
The appropriateness of any instrument
used to assess symptoms is not considered in
this review, but as patients become more ill
and less able to complete longer or more com-
plex questionnaires, this consideration be-
comes important. The use of proxies at the
end of life, explored for other popula-
tions,87– 89 may also be important, not only
because of decline in the final days of life but
also because confusion is common in the final
stages of ESRD. The fact that symptom prev-
alence is comparable to other end-of-life pop-
ulations suggests, at least in terms of symp-
toms, some degree of commonality between
those approaching the end of life with kidney
disease and those with other cancer and non-
cancer conditions. Understanding the extent
and limits of any common pathway will be
invaluable, and this approach emphasizes the
importance of collaboration and sharing ex-
pertise between those working in the nephrol-
ogy field (who are most familiar with aspects
specific to kidney disease) and those working
in palliative care (more familiar with end-of-
life course and trajectories).
One of the limitations of this systematic
Fatigue Myoclonus Nausea Pain Period of
% % % % Prevalence
25 28 13 42 Last 24 hours of
life
4 1 5 Last 24 hours of
life
review was the difficulty of developing a
search strategy that was sufficiently sensitive
(encompassing all possible symptoms), yet
specific enough to be manageable. Initial
searching and literature review, drawing on
studies such as those by Parfrey46,47 and by
Curtin et al 38 (which included patient inter-
views to identify symptoms), was necessary to
inform the search strategy. However, this was
a circular process that may have introduced
bias into the literature search because only
symptoms already recognized were then in-
cluded in the search. This problem is com-
pounded by the fact that symptoms may often
go unrecognized in ESRD, as already de-
scribed by both Weisbord and colleagues14
and by Davison,15 and highlights again the
urgent need for future research to describe the
whole range of symptoms and the total symp-
tom burden in ESRD.
Conclusions
Understanding symptoms is becoming in-
creasingly important, as the numbers of older
ESRD patients are rising, as the dialysis pop-
ulation grows, and as conservative manage-
ment (without renal replacement therapy)
becomes more common. This review demon-
strates the considerable gaps that remain in
understanding the symptoms that patients
with ESRD experience but indicates that these
patients have a high prevalence of symptoms
and considerable symptom burden. Consider-
able need exists to prioritize research into the
incidence and prevalence of symptoms in
ESRD, the causes of these symptoms, and
interventions to relieve them. Longitudinal
studies to explore change in symptoms over
time are urgently needed, and particular at-
tention needs to be paid to the end-of-life
period, both in dialysis withdrawal and in
 Symptoms in End-Stage Renal Disease
conservative management, where useful in-
formation on symptoms is sadly lacking. Re-
search that cuts across disease boundaries is
likely to be valuable, both to identify what is
common and what is different for those dying
with ERSD and to understand the extent to
which research evidence available from other
palliative populations may or may not be ap-
plicable. The impact of comorbidity and dis-
ease severity also need to be more fully un-
derstood. Building on this foundation, studies
of interventions to alleviate symptoms are
then needed, so that the quality of life of the
increasing numbers of people living with
ESRD can be effectively improved.
Acknowledgments
Thanks to Farida Malik for assistance in reviewing.
References
1. Feest TG, Mistry CD, Grimes DS, et al: Incidence of
advanced chronic renal failure and the need for end
stage renal replacement treatment. BMJ 301:897-900,
1990
2. Ansell D, Feest T (eds): UK Renal Registry Report
2003. Bristol, UK, UK Renal Registry, 2004
3. Ismail N, Hakim RM, Oreopoulos DG, et al: Renal
replacement therapies in the elderly: Part 1. Hemodi-
alysis and chronic peritoneal dialysis. Am J Kidney
Dis 22:759-782, 1993
4. US Renal Data System: USRDS 2001 Annual Data
Report. Bethesda, MD, National Institute of Diabetes
and Digestive and Kidney Diseases, 2001
5. Roderick P, Davies R, Jones C, et al: Simulation model
of renal replacement therapy: Predicting future de-
mand in England. Nephrol Dial Transplant 19:692-
701, 2004
6. Munshi SK, Vijayakumar N, Taub NA, et al: Outcome
of renal replacement therapy in the very elderly.
Nephrol Dial Transplant 16:128-133, 2001
7. Chandna SM, Schulz J, Lawrence C, et al: Is there a
rationale for rationing chronic dialysis? A hospital
based cohort study of factors affecting survival and
morbidity. BMJ 318:217-223, 1999
8. Lamping DL, Constantinovici N, Roderick P, et al:
Clinical outcomes, quality of life, and costs in the
North Thames Dialysis Study of elderly people on
dialysis: A prospective cohort study. Lancet 356:1543-
1550, 2000
9. Joly D, Anglicheau D, Alberti C, et al: Octogenarians
reaching end-stage renal disease: Cohort study of
decision-making and clinical outcomes. J Am Soc
Nephrol 14:1012-1021, 2003
10. Smith C, Silva-Gane M, Chandna S, et al: Choosing
not to dialyse: Evaluation of planned non-dialytic
97
management in a cohort of patients with end-stage
renal failure. Nephron Clin Pract 95:c40-c46, 2003
11. Singer PA, Martin DK, Kelner M: Quality end-of-life
care: Patients’ perspectives. JAMA 281:163-168, 1999
12. Steinhauser KE, Christakis NA, Clipp EC, et al: Fac-
tors considered important at the end of life by pa-
tients, family, physicians, and other care providers.
JAMA 284:2476-2482, 2000
13. Cohen LM, Germain M, Poppel DM, et al: Dialysis
discontinuation and palliative care. Am J Kidney Dis
36:140-144, 2000
14. Weisbord SD, Carmody SS, Bruns FJ, et al: Symptom
burden, quality of life, advance care planning and the
potential value of palliative care in severely ill hae-
modialysis patients. Nephrol Dial Transplant 18:1345-
1352, 2003
15. Davison SN: Pain in hemodialysis patients: Preva-
lence, cause, severity, and management. Am J Kidney
Dis 42:1239-1247, 2003
16. Kimmel PL, Emont SL, Newmann JM, et al: ESRD
patient quality of life: Symptoms, spiritual beliefs,
psychosocial factors, and ethnicity. Am J Kidney Dis
42:713-721, 2003
17. Frank A, Auslander GK, Weissgarten J: Quality of life
of patients with end-stage renal disease at various
stages of the illness. Soc Work Health Care 38:1-27,
2003
18. Iliescu EA, Coo H, McMurray MH, et al: Quality of
sleep and health-related quality of life in haemodialy-
sis patients. Nephrol Dial Transplant 18:126-132, 2003
19. Curtis BM, Barret BJ, Jindal K, et al: Canadian survey
of clinical status at dialysis initiation 1998 –1999: A
multicenter prospective survey. Clin Nephrol 58:282-
288, 2002
20. Martin CR, Thompson DR: Prediction of quality of life
in patients with end-stage renal disease. Br J Health
Psychol 5:41-55, 2000
21. Merkus MP, Jager KJ, Dekker FW, et al: Physical
symptoms and quality of life in patients on chronic
dialysis: results of The Netherlands Cooperative
Study on Adequacy of Dialysis (NECOSAD). Nephrol
Dial Transplant 14:1163-1170, 1999
22. O’Donnell K, Chung JY: The diagnosis of major de-
pression in end-stage renal disease. Psychother Psy-
chosom 66:38-43, 1997
23. Virga G, Mastrosimone S, Amici G, et al: Symptoms in
hemodialysis patients and their relationship with bio-
chemical and demographic parameters. Int J Artif
Organs 21:788-793, 1998
24. Balaskas EV, Chu M, Uldall RP, et al: Pruritus in
continuous ambulatory peritoneal dialysis and hemo-
dialysis patients. Perit Dial Int 13:S527-S532, 1993
(Suppl 2)
25. Collado-Seidel V, Kohnen R, Samtleben W, et al:
Clinical and biochemical findings in uremic patients
with and without restless legs syndrome. Am J Kid-
ney Dis 31:324-328, 1998
26. Farmer CJ, Snowden SA, Parsons V: The prevalence
of psychiatric illness among patients on home haemo-
dialysis. Psychol Med 9:509-514, 1979
27. Hammer J, Oesterreicher C, Hammer K, et al: Chronic
98 Murtagh, Addington-Hall, and Higginson
gastrointestinal symptoms in hemodialysis patients.
Wien Klin Wochenschr 110:287-291, 1998
28. Masi CM, Cohen EP: Dialysis efficacy and itching in
renal failure. Nephron 3:257-261, 1992
29. Parfrey PS, Vavasour H, Bullock M, et al: Symptoms
in end-stage renal disease: Dialysis v transplantation.
Transplant Proc 19:3407-3409, 1987
30. Walker S, Fine A, Kryger MH: Sleep complaints are
common in a dialysis unit. Am J Kidney Dis 26:751-
756, 1995
31. Antoniazzi AL, Bigal ME, Bordini CA, et al: Headache
and hemodialysis: A prospective study. Headache
43:99-102, 2003
32. Craven JL, Rodin GM, Littlefield C: The Beck Depres-
sion Inventory as a screening device for major depres-
sion in renal dialysis patients. Int J Psychiatry Med
18:365-374, 1988
33. Devins GM, Armstrong SJ, Mandin H, et al: Recurrent
pain, illness intrusiveness, and quality of life in end-
stage renal disease. Pain 42:279-285, 1990
34. Hong BA, Smith MD, Robson AM, et al: Depressive
symptomatology and treatment in patients with end-
stage renal disease. Psychol Med 17:185-190, 1987
35. Lopes AA, Bragg J, Young E, et al: Depression as a
predictor of mortality and hospitalization among he-
modialysis patients in the United States and Europe.
Kidney Int 62:199-207, 2002
36. McCann K, Boore JR: Fatigue in persons with renal
failure who require maintenance haemodialysis. J
Adv Nurs 32:1132-1142, 2000
37. Smith MD, Hong BA, Robson AM: Diagnosis of de-
pression in patients with end-stage renal disease.
Comparative analysis. Am J Med 79:160-166, 1985
38. Curtin RB, Bultman DC, Thomas-Hawkins C, et al:
Hemodialysis patients’ symptom experiences: Effects
on physical and mental functioning. Nephrology
Nurs J 29:562, 567-74, 2002
39. Gigli GL, Adorati M, Dolso P, et al: Restless legs
syndrome in end-stage renal disease. Sleep Med
5:309-315, 2004
40. Walters BA, Hays RD, Spritzer KL, et al: Health-
related quality of life, depressive symptoms, anemia,
and malnutrition at hemodialysis initiation. Am J
Kidney Dis 40:1185-1194, 2002.
41. Watnick S, Kirwin P, Mahnensmith R, et al: The
prevalence and treatment of depression among pa-
tients starting dialysis. Am J Kidney Dis 41:105-110,
2003
42. Cohen LM, Germain MJ, Poppel DM, et al: Dying well
after discontinuing the life-support treatment of dial-
ysis. Arch Intern Med 160:2513-2518, 2000
43. Barrett BJ, Vavasour HM, Major A, et al: Clinical and
psychological correlates of somatic symptoms in pa-
tients on dialysis. Nephron 55:10-15, 1990
44. Curtin RB, Bultman DC, Thomas-Hawkins C, et al:
Hemodialysis patients’ symptom experiences: Effects
on physical and mental functioning. Nephrol Nurs J
29:562, 567-575, 598, 2002
45. Merkus MP, Jager KJ, Dekker FW, et al: Quality of life
over time in dialysis: The Netherlands Cooperative
Study on the Adequacy of Dialysis. NECOSAD Study
Group. Kidney Int 56:720-728, 1999
46. Parfrey PS, Vavasour HM, Henry S, et al: Clinical
features and severity of nonspecific symptoms in di-
alysis patients. Nephron 50:121-128, 1988
47. Parfrey PS, Vavasour H, Bullock M, et al: Develop-
ment of a health questionnaire specific for end-stage
renal disease. Nephron 52:20-28, 1989
48. al Hihi E, Awad A, Hagedorn A: Screening for de-
pression in chronic hemodialysis patients. Mo Med
100:266-268, 2003
49. Hinrichsen GA, Lieberman JA, Pollack S, et al: De-
pression in hemodialysis patients. Psychosomatics 30:
284-289, 1989
50. Kutner NG, Fair PL, Kutner MH: Assessing depres-
sion and anxiety in chronic dialysis patients. J Psy-
chosom Res 29:23-31, 1985
51. Rodin G, Voshart K: Depressive symptoms and func-
tional impairment in the medically ill. Gen Hosp
Psychiatry 9:251-258, 1987
52. Walters BA, Hays RD, Spritzer KL, et al: Health-
related quality of life, depressive symptoms, anemia,
and malnutrition at hemodialysis initiation. Am J
Kidney Dis 40:1185-1194, 2002
53. Wuerth D, Finkelstein SH, Ciarcia J, et al: Identifica-
tion and treatment of depression in a cohort of pa-
tients maintained on chronic peritoneal dialysis. Am J
Kidney Dis 37:1011-1017, 2001
54. Wuerth D, Finkelstein SH, Finkelstein FO: The iden-
tification and treatment of depression in patients
maintained on dialysis. Semin Dial 18:142-146, 2005
55. Daut RL, Cleeland CS, Flanery RC: Development of
the Wisconsin Brief Pain Questionnaire to assess pain
in cancer and other diseases. Pain 17:197-210, 1983
56. Melzack R: The McGill Pain Questionnaire: Major
properties and scoring methods. Pain 1:277-299, 1975
57. Balaskas EV, Bamihas GI, Karamouzis M, et al: His-
tamine and serotonin in uremic pruritus: Effect of
ondansetron in CAPD-pruritic patients. Nephron 78:
395-402, 1998
58. Subach RA, Marx MA: Evaluation of uremic pruritus
at an outpatient hemodialysis unit. Ren Fail 24:609-
614, 2002
59. Szepietowski JC, Sikora M, Kusztal M, et al: Uremic
pruritus: A clinical study of maintenance hemodialy-
sis patients. J Dermatol 29:621-627, 2002
60. Winkelman JW, Chertow GM, Lazarus JM: Restless
legs syndrome in end-stage renal disease. Am J Kid-
ney Dis 28:372-378, 1996
61. Zucker I, Yosipovitch G, David M, et al: Prevalence
and characterization of uremic pruritus in patients
undergoing hemodialysis: Uremic pruritus is still a
major problem for patients with end-stage renal dis-
ease. J Am Acad Dermatol 49:842-846, 2003
62. Hui DS, Wong TY, Ko FW, et al: Prevalence of sleep
disturbances in Chinese patients with end-stage renal
failure on continuous ambulatory peritoneal dialysis.
Am J Kidney Dis 36:783-788, 2000
63. Cirignotta F, Mondini S, Santoro A, et al: Reliability of
a questionnaire screening restless legs syndrome in
patients on chronic dialysis. Am J Kidney Dis 40:302-
306, 2002
64. Unruh ML, Levey AS, D’Ambrosio C, et al: Restless
Legs symptoms among incident dialysis patients: As-
 Symptoms in End-Stage Renal Disease
sociation with lower quality of life and shorter
survival. Am J Kidney Dis 43:900-909, 2004
65. Mucsi I, Molnar MZ, Ambrus C, et al: Restless legs
syndrome, insomnia and quality of life in patients on
maintenance dialysis. Nephrol Dial Transplant 20:
571-577, 2005
66. Siddiqui S, Kavanagh D, Traynor J, et al: Clinical
aspects of restless legs syndrome in patients on
chronic haemodialysis. Renal Association Annual
Conference Proceedings, 2004
67. Kavanagh D, Siddiqui S, Geddes CC: Restless legs
syndrome in patients on dialysis. Am J Kidney Dis
43:763-771, 2004
68. Walters AS, LeBrocq C, Dhar A, et al: Validation of
the International Restless Legs Syndrome Study
Group rating scale for restless legs syndrome. Sleep
Med 4:121-132, 2003
69. Devins GM, Edworthy SM, Paul LC, et al: Restless
sleep, illness intrusiveness, and depressive symptoms
in three chronic illness conditions: Rheumatoid arthri-
tis, end-stage renal disease, and multiple sclerosis.
J Psychosom Res 37:163-170, 1993
70. Han SY, Yoon JW, Jo SK, et al: Insomnia in diabetic
hemodialysis patients. Prevalence and risk factors by
a multicenter study. Nephron 92:127-132, 2002
71. Sabbatini M, Minale B, Crispo A, et al: Insomnia in
maintenance haemodialysis patients. Nephrol Dial
Transplant 17:852-856, 2002
72. Venmans BJ, van Kralingen KW, Chandi DD, et al:
Sleep complaints and sleep disordered breathing in
hemodialysis patients. Neth J Med 54:207-212, 1999
73. Holley JL, Nespor S, Rault R: A comparison of re-
ported sleep disorders in patients on chronic hemo-
dialysis and continuous peritoneal dialysis. Am J Kid-
ney Dis 19:156 –116, 1992
74. Locking-Cusolito H, Huyge L, Strangio D: Sleep pat-
tern disturbance in hemodialysis and peritoneal dial-
ysis patients. Nephrol Nurs J 28:40-44, 2001
75. Stepanski E, Faber M, Zorick F, et al: Sleep disorders
in patients on continuous ambulatory peritoneal di-
alysis. J Am Soc Nephrol 6:192-197, 1995
76. Yasuda G, Shibata K, Takizawa T, et al: Prevalence of
constipation in continuous ambulatory peritoneal di-
alysis patients and comparison with hemodialysis
patients. Am J Kidney Dis 39:1292-1299, 2002
77. Min F, Tarlo SM, Bargman J, et al: Prevalence and
causes of cough in chronic dialysis patients: A com-
parison between hemodialysis and peritoneal dialysis
patients. Adv Perit Dial 16:129-133, 2000
99
78. Cohen LM, Dobscha SK, Hails KC, et al: Depression
and suicidal ideation in patients who discontinue the
life-support treatment of dialysis. Psychosom Med
64:889-896, 2002
79. Portenoy RK: Cancer pain: General design issues, in
Max MB, Portenoy RK, Laska EM (eds): The Design of
Analgesic Clinical Trials. New York, NY: Raven, 1991,
pp 233-266
80. Bruera E, Watanabe S: New developments in the
assessment of pain in cancer patients. Support Care
Cancer 2:312-318, 1994
81. Portenoy RK, Thaler HT, Kornblith AB, et al: The
Memorial Symptom Assessment Scale: An instrument
for the evaluation of symptom prevalence, character-
istics and distress. Eur J Cancer 30A:1326-1336, 1994
82. Weisbord SD, Fried LF, Arnold RM, et al: Develop-
ment of a symptom assessment instrument for
chronic hemodialysis patients: The Dialysis Symptom
Index. J Pain Symptom Manage 27:226-240, 2004
83. Ritz E, Rychlik I, Locatelli F, et al: End-stage renal
failure in type 2 diabetes: A medical catastrophe of
worldwide dimensions. Am J Kidney Dis 34:795-808,
1999
84. Vainio A, Auvinen A: Prevalence of symptoms
among patients with advanced cancer: An interna-
tional collaborative study. Symptom Prevalence
Group. J Pain Symptom Manage 12:3-10, 1996
85. Solano JP, Gomes B, Higginson IJ: A comparison of
symptom prevalence in far advanced cancer, AIDS,
heart disease, chronic obstructive pulmonary disease
and renal disease. J Pain Symptom Manage 31:58-69,
2006
86. Franks PJ, Salisbury C, Bosanquet N, et al: The level of
need for palliative care: A systematic review of the
literature. Palliat Med 14:93-104, 2000
87. Nekolaichuk CL, Bruera E, Spachynski K, et al: A
comparison of patient and proxy symptom assess-
ments in advanced cancer patients. Palliat Med 13:
311-323, 1999
88. Higginson I, Priest P, McCarthy M: Are bereaved
family members a valid proxy for a patient’s assess-
ment of dying? Soc Sci Med 38:553-557, 1994
89. Klinkenberg M, Smit JH, Deeg DJ, et al: Proxy report-
ing in after-death interviews: The use of proxy re-
spondents in retrospective assessment of chronic dis-
eases and symptom burden in the terminal phase of
life. Palliat Med 17:191-201, 2003