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Health-related quality of life of children and adolescents with CKD stages 4-5
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Health-related quality of life of children
and adolescents with CKD stages 4–5 and
their caregivers

Marcos Lopes, Alexandre Ferraro & Vera

H. Koch

Pediatric Nephrology
Journal of the International Pediatric
Nephrology Association

ISSN 0931-041X

Pediatr Nephrol
DOI 10.1007/s00467-014-2769-8

1 23
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 Author's personal copy
Pediatr Nephrol
DOI 10.1007/s00467-014-2769-8
ORIGINAL ARTICLE
Health-related quality of life of children and adolescents
with CKD stages 4–5 and their caregivers
Marcos Lopes & Alexandre Ferraro & Vera H. Koch
Received: 19 June 2013 / Revised: 28 December 2013 / Accepted: 20 January 2014
# IPNA 2014
Abstract
Background Renal replacement therapies may affect the qual-
ity of life of patients and their primary caregivers (PC).
Methods This study describes the perception of health-related
quality of life (HRQoL) of children/adolescents with CKD
stages 4–5, as well as of their PC (n=64), in comparison to
healthy peers and their PC (n=129), respectively, based on the
Peds QL™ 4.0 and Short Form-36 (SF-36) questionnaires and
selected biomarkers.
Results Patients reported a deleterious impact on physical
capacity and on social and school activities. A negative influ-
ence on emotional aspects was reported by older patients, but
not by their PC. Hemodialysis, followed by peritoneal dialy-
sis, had a more negative impact on patients’ physical func-
tioning domain. PC HRQol proxy reports differed from those
of their children, especially in older patients. PC of both
groups presented similar SF-36 scores. An association was
demonstrated between the magnitude of treatment target in-
adequacies, lower specific dominion scores in the patients/PC
proxy reports and PC SF-36 general health scores.
Conclusion The HRQoL of patients with CKD stages 4–5 is
negatively affected to different degrees depending on age and
treatment modality. The results suggest an association be-
tween worsening HRQoL parameters and inadequate control
of recognized therapeutic CKD treatment targets.
Keywords Quality of life . Kidney failure . Chronic . Child .
Adolescent . Caregivers . Questionnaires
M. Lopes : V. H. Koch (*)
Department of Pediatrics, Pediatric Nephrology Unit, Instituto da
Criança Hospital das Clinicas of the University of Sao Paulo Medical
School, Rua das Mangabeiras 91/81, 01233-010 São Paulo, Brazil
e-mail: vkoch@terra.com.br
A. Ferraro
Department of Pediatrics, Discipline of Preventive Medicine,
University of Sao Paulo Medical School, São Paulo, Brazil
Introduction
According to the Kidney Disease Outcomes Quality Initiative
(K/DOQI) of the National Kidney Foundation (NKF), chronic
kidney disease (CKD) is defined by structural or functional
abnormalities of the kidney for ≥3 months, with or without
decreased glomerular filtration rate (GFR), or by a GFR of
<60 mL/min/1.73 m2 for ≥3 months [1].
Therapeutic approaches to CKD in childhood present a
challenge due to the different characteristics of each period of
growth and development [2]. The aim of any treatment is to
minimize renal damage and reduce complications, but as kid-
ney function is gradually lost, it is necessary to adopt renal
replacement therapy (RRT) in the form of hemodialysis (HD),
peritoneal dialysis (PD) or renal transplantation (renal TX)
[1–4]. RRT imposes adaptations in the child’s everyday routine,
it affects interaction with peers, school attendance and physical
activity, and it restricts social interaction to a universe mostly
composed of other patients and healthcare professionals [3–6].
Chronically ill children often have physical or cognitive
limitations which increase their dependence on care provided
by healthcare professionals and especially by their families,
who take most of the responsibility for the success of treat-
ment [7]. However, primary caregivers (PC) may present
psychological and emotional conditions that hinder their par-
ticipation in the demands of chronic disease therapeutic inter-
ventions [8, 9]. These difficulties may lead to socio-emotional
problems, such as isolation and feelings of dissatisfaction,
frustration and desperation. In this context, family conflicts
develop and influence the child’s behavior during the treat-
ment [8, 9]. On the other hand, a positive family environment
protects the child and results in high adherence to treatment
and positive clinical indicators [7, 9, 10].
The aim of this study is to describe the health-related
quality of life (HRQoL) of children and adolescents with
CKD stage 4 (pre-dialysis) or stage 5 (dialysis/transplanta-
tion), as well as of their PC, and compare this to that of a
 Author's personal copy
healthy control group. We have also evaluated the association
between the PC HRQoL scores and selected laboratory bio-
markers of the patients and their PC.
Methods
Patient and control group participants
This is a cross-sectional, descriptive, comparative and analyti-
cal study in which patients with CKD stages 4–5 aged 1–18
years and their PC were followed at the Pediatric Nephrology
Unit of “Instituto da Criança” of the Hospital das Clínicas of the
University of São Paulo Medical School, as well as a control
group of healthy age-paired children/adolescents and their PC.
The study protocol was approved by the Ethics Committee of
the Hospital das Clínicas of the University of São Paulo Med-
ical School (registration number 0082/10). The children/
adolescents in the control group was recruited at a
kindergarten/ elementary school and at a routine pediatric
follow-up outpatient clinic falling under the supervision of the
University of São Paulo Department of Education and Depart-
ment of Public Health, respectively. Kindergarten/ elementary
school PC were invited to participate in the study by telephone
or letter, while routine pediatric follow-up outpatient clinic PC
participants were contacted personally in the clinic waiting
room. The inclusion criteria for the children/adolescents were:
(1) age ranging from 2 to 18 years; (2) capacity to understand
the questions, which was evaluated by asking the participant
simple questions while explaining the study objectives, the
instrument and the routine to be followed to fill in the ques-
tionnaire; (3) acceptance to participate in study and signature of
the PC on the Informed Consent Form. The patient and control
groups were evaluated in a 1:2 ratio, so that two age-matched
controls were recruited for each patient. The patients and their
PC answered the questionnaire during an outpatient clinic visit
or during dialysis. Most of the participants in the control group
were recruited in the routine pediatric outpatient clinic. No
control group child/adolescent participant reported chronic dis-
eases. The control group participants answered the question-
naires in a secluded area that adjoined the clinic waiting room.
Quality of life questionnaires
PedsQL™ 4.0—generic core scales
Children/adolescents report and PC report PedsQL™ 4.0 is a
modular approach to measuring HRQoL in healthy children
and adolescents and those with acute and chronic health
conditions, which has been validated in Brazil. The question-
naire evaluates four scales (physical, emotional, social and
school functioning) in 23 questions using age-specific forms.
Self-report forms are available for children/adolescents in the
Pediatr Nephrol
age groups of 5–7, 8–12 or 13–18 years. Parent-proxy reports
are available for children in the age groups of 2–4, 5–7, 8–12
or 13–18 years. The questionnaire score ranges from zero to
100 in each scale, with higher values interpreted as indicating
a better quality of life (QoL) [11, 12].
Short Form-36
The Short-Form-36 health status questionnaire (SF-36) is a
self-report instrument, validated in Brazil, for generic evalua-
tion of adult health. It contains 36 questions distributed in
eight domains (functional capacity, physical aspects, pain,
general health status, vitality, social aspects, emotional aspects
and mental health). The scores of each domain range from 0 to
100, where zero represents worse general health status and
100 represents excellent health. Question number 2 assesses
the frequency of health changes that occurred in the previous
year; it is not included in any of the above-mentioned domains
and requires separate analysis [13].
Magnitude of inadequacy in selected CKD laboratory
parameters
Desirable treatment targets for hemoglobin (≥11 mg/dl), albu-
min (≥3.5 g/dl) and sodium bicarbonate (≥22 mEq/L) were
defined based on achievable levels in good routine clinical
practice. The magnitude of inadequacy for these selected
parameters was measured during two clinic visits timed close
to the appointment for completion of the HRQoL question-
naire. The results were rated as good (2) for no abnormal
results, moderate (1) for confirmed abnormal results in one
parameter and severe (0) for confirmed abnormal results in
two parameters.
Statistical analysis
The score distributions of each domain of the Peds QL™ 4.0
and SF-36 scales were described as median and interquartile
range (25–75th percentiles). The Kruskal–Wallis test was used
to compare age groups and domains of Peds QL™ 4.0 and to
compare the frequency of responses to the SF-36 question.
The Wilcoxon signed-rank test was used to compare each
domain of the children/adolescents and PC reports of Peds
QL™ 4.0 in each group separately. A p value of <0.05 was
considered to be significant. Analyses were performed using
Stata 10.1 (StataCorp, College Station, TX).
Results
The patient group was composed of 64 participants aged 2–
18 years, of whom the majority were male and aged 8–12 years,
and their PC. Of these 64 patients, 21 were on conservative
 Author's personal copy
Pediatr Nephrol
management, 25 were prevalent dialysis patients (13 on PD and
12 on HD) and 18 were prevalent renal TX patients. For 54
children aged 5–18 years, both a child self-report and a parent
proxy-report were available. Eight patients initially eligible for
inclusion in the study were disqualified on account of
neurodevelopmental deficits. Two PC in the patient group re-
fused to participate in the study. The control group included 129
age–paired children/adolescents and their PC. Table 1 presents
the distribution of children/adolescents and their PC in the
patient and control groups according to demographic character-
istics, treatment modalities and social and clinical aspects. One-
third of our patients presented either special urine elimination
requirements, due to the presence of continent or non-continent
stoma, or mobility issues, associated with the need to use a
wheelchair.
The Peds QL™ 4.0 Scale took an average of 10 min to be
completed. PC and patients had no problem in understanding
the questions or completing the instrument forms. The
HRQoL scores of patients were significantly lower than those
of the healthy control participants and their PC in the physical,
social and school functioning domains, as shown in Table 2,
which depicts the comparison between the answers of
children/adolescents and their PC in the four Peds QL™ 4.0
domains for both groups. Self-report forms for the Peds QL™
4.0 questionnaire are available for children/ adolescents in the
age groups 5–7, 8–12 or 13–18 years and parent-proxy reports
are available for children/adolescents in the age groups 2–4,
5–7, 8–12 or 13–18. Therefore, in order to enable calculations
of the school functioning scale, we excluded 14 PC reports
and seven self-reports of patients not attending school as
follows: seven from patients in the age range of 2–4 years,
two in the age range 5–7 years, three in the age range 8–
12 years and two in the age range 13–18 years. The same
procedure was adopted for three PC reports from the control
group participants (all three in the age group 2–4 years).
Patients undergoing either form of dialysis reported lower
HRQoL than those in conservative treatment or post renal TX
follow-up; the same opinion was not shared by their PC, whose
parent-proxy scores did not show differentiated HRQoL across
different treatment modalities. Table 3 details the Peds QL™
4.0 score analysis of the reports of children/adolescents and
their PC according to RRT treatment modalities.
Comparison of the answers reported by the PC of both
study groups to the 36 questions constituting the eight do-
mains of the SF-36 (functional capacity, physical aspects,
pain, general status of health, vitality, social aspects, emotion-
al aspects and mental health) showed comparable mean
HRQoL values. Table 4 presents the distribution of the SF-
26 scores for the PC of the patient group according to their
child’s CKD treatment modality. The scores show that al-
though no difference was perceived in the comparison be-
tween the SF-36 scores of both groups of PC, CKD treatment
modality negatively affected the “general status of health” of
parents whose children were receiving conservative treatment
and HD.
The analysis of selected CKD treatment targets showed a
significant association between lower Peds QL™ 4.0 parent-
proxy scores for physical, emotional and social functioning
and patients’ self-report of emotional functioning scores, with
treatment target inadequacies of severe magnitude, as shown
in Table 5.
Figure 1 shows the distribution of the scores of each domain
of the Peds QL™ 4.0 by child’s age as observed in the child/
adolescent report and parent-proxy report in both the patient
and control groups. The progressively negative effect of age on
the patients’ HRQoL perception across social, emotional and
school functioning domains of the Peds QL™ 4.0 questionnaire
is clearly shown, especially in children aged >8 years. These
results have different trends in comparison with their control
peers’ responses, as well as with the perception of their PC-
proxy. The study patients’ PC had a worse perception of
physical, social and school functioning in their children’s first
years of life with progressive improvement in later years and
sensed their children’s emotional functioning as stable.
Discussion
This study evaluated the HRQoL of children/adolescents with
CKD stages 4–5 and their PC, comparing them with a healthy
age-paired control group. The instruments used for this pur-
pose were the Peds QL™ 4.0—children/adolescents and
parent-proxy reports and the SF-36 questionnaires.
The predominant age range and gender of our patients are
consistent with those of other series described in the literature
[2, 5, 14–16]. The high frequency of children with special
needs in terms of urination and mobility in our cohort reflect
the late diagnosis, late referral and the paucity of tertiary care
facilities specialized in pediatric nephro-urological cases in
Brazil, which increase the likelihood of patients with lower
urinary tract malformations and spina bifida reaching CKD
stages 4–5 at earlier ages [17].
Our results confirm that patients with CKD stages 4–
present a greater impairment in physical, social and school
functioning than their healthy peers. Older patients reported a
more pronounced negative impact in these domains, as well as
in emotional aspects. Goldstein et al. [5], using Peds QL™
4.0, demonstrated that HRQoL scores for all domains were
significantly lower in CKD stage 5 patients than in healthy
controls. López et al. [4] evaluated HRQoL scores in patients
with CKD stage 4–5 using MOS-SF-20™ (20–Item Medical
Outcomes Study) and identified significantly worse scores in
general self-esteem, physical performance and physical activ-
ity, without an significant difference in socialization. In a
multicenter study from the Turkish Pediatric Kidney Trans-
plantation Study Group™, Buyan et al. [18] used the Turkish
 Author's personal copy
Pediatr Nephrol

Table 1 Distribution of the chil-

dren/adolescents and primary Distribution Patients (n=64) Control subjects
caregivers of the patient and con- (n=129)
trol groups according to gender,
age, chronic kidney stage, educa- Children/adolescents, n (%)
tional level and family Gender
composition Male 35 (55) 64 (49)
Female 29 (45) 65 (51)
Total 64 (100) 129 (100)
Age, years, n Stage 4 CKD Renal TX PD HD
2–4 5 1 3 1 20 (16)
5–7 2 4 4 1 20 (16)
8–12 7 9 5 5 55 (42)
13–18 7 4 1 5 34 (26)
Total 21 18 13 12 129 (100)
Primary caregivers, n (%)
Gender
Male 7 (11 ) 21 (16)
Female 57 (89) 108 (84)
Total 64 (100) 129 (100)
Age, years, n (%)
19–37 31 (48) 43 (33)
38–50 31 (48) 67 (52)
51–73 2 (4) 19 (15)
Total 64 (100) 129 (100)
Years of education, n (%)
<8 27 (42) 51 (40)
9–12 29 (45) 44 (34)
>13 08 (13) 34 (26)
Total 64 (100) 129 (100)
Family composition, n (%)
Mother only 2 (3) 5 (4)
Father only 1 (2) –
CKD, Chronic kidney disease; Mother and father 11 (17) 36 (28)
renal TX, renal transplantation; Mother, father, brothers and others 50 (78) 88 (68)
HD, hemodialysis; PD, peritoneal Total 64 (100) 129 (100)
dialysis

versions of the Kinder Lebensqualität Fragebogen
(KINDL™) questionnaires to evaluate 211 children/
adolescents with CKD stage 5 aged 4–18 years from 11
university hospitals, as well as 232 age-matched healthy chil-
dren and adolescents. These authors showed that the CKD
patients had lower scores in all subscales except for physical
well-being. Heath et al. [19], however, using the Generic
Children’s Quality of Life Measure™ (GCQ) in 225 pediatric
patients with stages 4–5 CKD from seven UK centers, showed
that in comparison with data from the general population,
renal patients had a higher GCQ QoL score. Analysis of the
whole group of renal patients revealed no significant differ-
ence between the mean GCQ scores of participants in various
treatment modalities and no significant differences between
gender and age group [19]. This disparity of results has to be
interpreted with caution due to the heterogeneity of HRQoL
instruments and the potential difficulty in comparing these
scores. It should be noted, however, that all of these studies
compared perceived HRQoL between renal pediatric patients
and age-matched healthy children, which gives strength to the
results of our study which situates the study population in the
actual context of regional, social, economic, cultural and
healthcare conditions.
We also performed a concomitant evaluation of the
HRQoL of the PC. The realities of the new global conditions,
which influence economic, social and environmental issues
and profound implications for teaching and learning, for busi-
ness and politics, for human rights and human conflicts, are
motivating accelerating change and placing the global popu-
lation under stress [20]. Although caregiving is a normal part
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Pediatr Nephrol

Table 2 Comparison between the

scores of children/adolescents and Domain/distribution group Patient (n=54) Control (n=109) pa
their primary caregiver in the four
Peds QL™ 4.0 domains for both Physical functioning
the patient and control groups Children/adolescents 75 (59.11–88.28) 87.5 (76.56–93.75) 0.0001
Primary caregivers 88,39 (64.61–100) 93.75 (81.25–100) 0.0242
Emotional functioning
Children/adolescents 65 (55–80) 75 (55–85) 0.2195
Primary caregivers 87.50 (66.60–98.75) 85 (65–95) 0.8477
Social functioning
Children/adolescents 82.5 (61.87–95) 95 (80–100) 0.0093
Data are presented as the median Primary caregivers 90 (65–100) 95 (80–100) 0.0265
score with the interquartile range School functioning
(IQR; 25th–75th percentile) given Children/adolescents 65 (50–80) 80 (65–90) 0.0019
in parenthesis
a
Primary caregivers 60 (45–87.50) 85 (65–100) 0.0001
Kruskal–Wallis test (p<0.05)

of being the parent of a young child, this role takes on an
entirely different significance when a child experiences func-
tional limitations and possible long-term dependence. One of
the main challenges for parents is to manage their child’s
chronic health problems effectively and juggle this role with
the requirements of everyday living [21]. The diagnosis of
CKD confronts the PC, usually the mother, with a difficult
reality, resulting in pressure and problems related to living
with a chronic disease at home. To single out the impact of
chronic disease at home we evaluated the PC of healthy kids
for comparison.
Our choice to assess the impact of advanced pediatric CKD
on the caregiver’s QoL is innovative, since previous studies
with families of advanced CKD children have disregarded the
degree of interference that the disease causes in family life,
especially on those who are directly responsible for the suc-
cess of the child’s treatment. In our study, the PC of the patient
group were predominantly young parents, with only a few
years of education, which might suggest that their children’s
disease status would interfere with the natural progression of
their lives. However, the total QoL scores for both groups
were similar, which may be related to the same general diffi-
culties which affect two groups of individuals with compara-
ble socioeconomic and cultural levels. The need for the PC to
postpone personal needs and face repetitive limitations in
favor of their child’s well-being may be the reason for the

Table 3 Distribution and comparison of the scores obtained in the four Peds QL™ 4.0 domains for the patient (n = 44) and their primary caregiver
(n = 64) according to chronic kidney disease (CKD) treatment modality

Domain/distribution Conservative treatment—CKD Renal TX Peritoneal dialysis Hemodialysis pb

group stage 4 (n PC=21)a (n PC=18) (n PC =13) (n PC=12)

Physical functioning
Children/adolescents 82.81 (64.84–93.75) 78.57 (67.18–93.75) 67.18 (55.46–82.81) 62.50 (53.12–68.75) 0.0229
Primary caregivers 89.28 (64.06–100) 95.31 (53.90–100) 90.62 (64.95–100) 75 (62.18–92.18) 0.6700
Emotional functioning
Children/adolescents 70 (56.5–88.75) 70 (60–82.5) 57.50 (37.50–76.25) 60 (50–80) 0.1190
Primary caregivers 80 (68.30–95) 90 (73.75–100) 90 (67.50–97.50) 75.80 (45.31–90) 0.2300
Social functioning
Children/adolescents 92,50 (82.50–98.75) 75 (60–92.50) 77.50 (57.50–100) 70 (55–90) 0.1018
Primary caregivers 90 (58.12–100) 95 (73.75–100) 70 (67.50–97.50) 82.50 (43.70–100) 0.4401
School functioning #
Children/adolescents 72,50 (48.75–81.25) 70 (60–83.75) 55 (41.25–70) 60 (47.50–85) 0.4237
Primary caregivers 65 (40–80) 90 (50–92.50) 47,50 (37.18–58.75) 60 (46.87–85) 0.1222

Data are presented as the median score with the IQR given in parenthesis
a
n PC, Number of primary caregivers (PC)
b
Kruskal-Wallis test (p<0.05)
TX, transplant
 Author's personal copy
Pediatr Nephrol

Table 4 Distribution of the SF-66 scores for the primary caregivers of the patient group (n=64) according to their child’s chronic kidney disease (CKD)
treatment modality

SF-36 domains Conservative treatment—CKD 4 (n=21) Renal TX (n=18) Peritoneal dialysis (n=13) Hemodialysis (n=12) pa

Functional capacity 95 (82.50–100) 100 (88.75–100) 95 (72.5–100) 90 (76.25–100) 0.333

Physical aspects 100 (50–100) 100 (100–100) 100 (62.5–100) 100 (31.25–100) 0.294
Pain 72 (46–100) 82.5 (59.5–100) 72 (46–92) 51 (42.75–93) 0.321
General status of health 67 (47–83.5) 83.5 (74.5–97) 82 (66–93.5) 62 (55.5–88) 0.010
Vitality 75 (42.5–82.5) 75 (55–86.25) 70 (47.5–80) 57.5 (42.5–77,5) 0.510
Social aspects 75 (50–100) 100 (75–100) 100 (56.25–100) 81.25 (62.5–100) 0.270
Emotional aspects 92 (33.3–100) 100 (85.5–100) 84 (33.3–100) 98 (66–100) 0.140
Mental health 68 (60–90) 82 (72–89) 80 (54–86) 74 (51–87) 0.470

Data are presented as the median score with the IQR given in parenthesis
a
Kruskal-Wallis test (p<0.05)
TX, transplant

association of a worse perception of general health presented by patients and their PC practically live on the road. Time spent in
the PC of children undergoing either conservative treatment, public transportation and time demanded for clinical care in
characterized by a multiplicity of dietary and pharmacological general takes up a great percentage of their daily routine and, by
interventions requiring frequent visits to the outpatient clinic, or the time they get home, it is up to the PC to perform routine
HD, which in our service is in-center and predominantly per- domestic chores, leaving no remaining time for personal needs.
formed daily, in comparison to those whose children are post Another aspect that has been discussed in similar studies is the
renal TX. This finding may be counter-intuitive: one of the influence of age on the perceived impact on the QoL of pediatric
possible explanations for this worse perception of general patients with CKD stages 4–5. Our patients have demonstrated
health is that our center is a tertiary care facility in a very busy worse scores of physical, emotional, social and school function-
metropolitan area, our patients generally live in the suburbs and ing with increasing age, and a discrepancy between the patient
due to the multiple necessities involved in the care of stage 4 and control group scores can be observed predominantly in the
CKD and daily HD patients, such as frequent clinic appoint- adolescent age range. Some hypotheses can be raised to justify
ments, laboratory or imaging tests and/or dialysis, many of our this finding. Chronic kidney impairment and prolonged use of
Table 5 Distribution the Peds QL™ 4.0—children/adolescents and parent-proxy report scores for children/adolescents (n=54) and primary caregivers
(n=64) according to the magnitude of treatment target inadequacies in the patient group

Domain/distribution group Magnitude of inadequacy for the selected parameters pa

0 1 2

Physical functioning
Children/adolescents 68.75 (56.25–80) 75 (60.93–85.93) 78.34 (55.46–93.75) 0.720
Primary caregivers 75 (54.68–90.62) 81.25 (50–97.65) 93.75 (80.35–100) 0.025
Emotional functioning
Children/adolescents 60 (60–80) 55 (42.50–77.50) 75 (60–86.25) 0.025
Primary caregivers 66.60 (55–85) 77.50 (63.75–91.25) 95 (85–100) 0.008
Social functioning
Children/adolescents 90 (70–100) 70 (60–90) 87.50 (67.50–95) 0.294
Primary caregivers 90 (60–100) 70 (55–95) 100 (72.50–100) 0.036
School functioning
Children/adolescents 75 (45–87.50) 60 (48.75–76.25) 72.50 (60–80) 0.298
Primary caregivers 75 (45–82.50) 57.50 (42.81–78.75) 67.50 (48.75–90) 0.632

Data are presented as the median score with the IQR given in parenthesis
The magnitude of inadequacy for the selected parameters was rated as good (2) for no abnormal results, moderate (1) for confirmed abnormal results in
one parameter and severe (0) for confirmed abnormal results in two parameters. 0: 11 children/ adolescents, 13 PC; 1: 22 children/ adolescents; 22 PC; 2:
22 children/ adolescents; 29 PC
a
Kruskal-Wallis test (p<0.05)
 Author's personal copy
Pediatr Nephrol

Physical function

Physical function
Emotional function

Emotional function
Social function

Social function
School function

School function

*Years old *Years old

Fig. 1 Distribution of median scores obtained in each domain of the Peds QL™ 4.0 - children/adolescents and primary caregivers (PC) reports in the
Patient (n=44; Fig. 1A) and Control (n=109; Fig. 1B) groups according to age by Wilcoxon signed-rank test

medication may lead to changes in physical appearance, such as
growth retardation and skeletal deformities; these changes can be
considered to be aggressive at a time when personal appearance
is the key to self-acceptance [15]. Additionally, the progressive
impact on QoL may be related to school activities, which moti-
vate a higher level of socialization with increasing autonomy
from parents. CKD, especially when dialysis is required, leads
to changes in the daily routine of the child/adolescent and
may tie the patient to the hospital environment, hindering
integration into the school routine. Renal TX represents an
independence from dialysis equipment and frequent in-hospital
activities, although the use of multiple medications remains
necessary. The favorable impact of renal TX on patients’ QoL
scores demonstrated in our study confirms the findings of
previous studies [3–5, 22–30].
Our comparison of QoL perceptions between PC and pa-
tients revealed more conflicting opinions than those observed
in the control group, with the opinions tending to diverge
progressively with age. These differences may suggest specif-
ic areas of miscommunication between family members and/
or a lack of autonomy of the child, leading to the PC
overestimating their child’s QoL. As most of the discrepancy
occurs with older children, this might be related to the inability
of the chronically ill adolescent to communicate personal
feelings and deal with the more profound impact of disease-
related restrictions in a period of life when independence and
 Author's personal copy
self-care are most cherished. This pattern of behavior may
lead the adolescent to isolation, psychological imbalance and
eventually non-compliance. Differences between the views of
patients and their PC should alert the healthcare team to
expand to the need to identify the child/adolescent’s real
anxieties and expectations as part of their daily routine [4,
24, 30–33]. A conflict of HRQoL perception between children
and PC has also been described in other similar studies. López
et al. [4] demonstrated that 9- to 12-year-old children and their
parents agreed in all QoL domains, while parents
underestimated social function and emotional well-being
when their children were older than 12 years [4]. Buyan
et al. [18] showed that concordance between parent-proxy
and child-self reports was only moderate for the majority of
the evaluated subscales. Using the Peds QL™ 3.0 end stage renal
disease (ESRD) module, Ki-Soo Park et al. [34] reported that
CKD stage 5 children self-reports showed significantly higher
QoL scores than parent-proxy reports in the domains of general
fatigue, family and peer interaction and worry. These authors
suggested that in the face of the potential discrepancy between
parent-proxy and child-self scores on QoL, children’s and
parents’ perspectives should be independently evaluated [34].
We also studied the association between QoL scores and
the magnitude of inadequacies found in selected ESRD treat-
ment targets. We chose hemoglobin, serum albumin and se-
rum bicarbonate as biomarkers, as these parameters depend on
a nutritional/medical prescription, which in our service fol-
lows a routine therapeutic protocol, as well as on the interac-
tion of the PC with the child/adolescent. As a consequence,
when the target values of these parameters are consistently not
achieved, non-compliance may be suspected. The highest
number of inadequacies was identified among patients under-
going conservative treatment, followed by PD. We demon-
strated an association between a higher magnitude of inade-
quacies with lower emotional scale scores in the patients’
reports, with lower physical, emotional and social scale scores
in the PC’ proxy reports and with lower caregivers SF-36
“general health” scores, suggesting that our theory might be
correct. The therapeutic management of stage 4 CKD is very
demanding, as many changes are made in the nutritional and
pharmacological management of the child with progressive
kidney damage in order to preserve metabolic and acid–base
balance; these changes place the PC and the patient under
daily stress. The same can be said about PD, which enforces a
heavy burden of responsibility on the PC for the patient’s
healthcare provision and therapeutic success. These findings
may suggest difficulties in family dynamics, especially in the
lack of caregivers’ courage and strength to enforce diet and
medication in the face of a child they consider to be in
emotional pain on account of the disease burden. This inno-
vative strategy of combined analysis of QoL scores and treat-
ment targets needs to be re-evaluated in other studies, as it
may be related to under-recognition of depression in patients
Pediatr Nephrol
and families as a facilitator to a communication gap between
the caregivers and the healthcare team and may prove to be a
major biomarker of non-compliance.
The main limitations to our study are related to its cross-
sectional design and to the relatively low number of patients
enrolled in the study, which belong to a single Brazilian
pediatric nephrology reference center. The division of the
cohort into four categories of CKD therapy (conservative,
PD, HD and post-renal TX) demonstrated the considerable
heterogeneity of HRQoL score between categories, but inter-
fered with the possibility of performing a multivariate analysis
of risk factors for low HRQoL in the described population.
For future studies, we recommend that patients should be
followed longitudinally with global (Peds QL™ 4.0) and
disease-specific (Peds QL™ 3.0 ESRD Module) HRQoL pe-
diatric CKD patient and proxy ratings, as described by Nuel
et al. [35], to whose protocol we would suggest the addition of
the PC HRQoL longitudinal evaluation with SF-36 and the
relationship of these scores with treatment targets. With this in
mind, we have already translated and culturally adapted the
Peds QL™ 3.0 ESRD Module in Brazil [36]. These instruments
can be easily completed in a secluded area of the waiting room
or during dialysis; through their routine utilization future studies
will be able to show which of them is better to evaluate quality
of care and effectiveness of a multi-disciplinary risk assessment
and management programs, or possibly their combined use will
prove to yield complementary information.
This approach will enable the healthcare team to follow the
impact of renal function deterioration and age on the HRQoL of
patients and their families, so that interventions can be targeted
to their needs. Hopefully this patient–family-centered approach
will mitigate non-compliance, favor global and specific patient
outcomes and shape the quality of care in pediatric CKD.
Conclusions
Our data confirm that children/adolescents with CKD stages
4–5 present lower HRQoL scores than their healthy peers and
that there is a progressive worsening of these parameters with
age. We found a tendency for disagreement between the QoL
reports of pediatric patients and their caregivers, which widens
with age, as caregivers often underestimate the effects of the
disease on their children’s QoL. The total QoL scores of
caregivers of the patient and control groups were similar,
except for lower “general health” scores in the patient group.
Caregivers’ “general health” scores were also lower in asso-
ciation with conservative treatment and HD treatment modal-
ities and in association with a greater magnitude of laboratory
parameter inadequacies.
The data related to the analysis of biochemical and hema-
tological markers suggest possible non-adherence. The need
for longitudinal studies to follow global and disease-specific
 Author's personal copy
Pediatr Nephrol
HRQoL pediatric CKD patient and parent-proxy ratings, PC
HRQoL scores and their relationship with selected CKD
biomarkers is suggested.
Acknowledgments This study was conducted with the support of the
Coordenação de Aperfeiçoamento de Pessoal de Nível Superior
(CAPES), the Brazilian government department dedicated to training
human resources. We thank Dr. J.W. Varni for permission to use the Peds
QL questionnaires and the MAPI Institute for their support.
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