Pediatr Nephrol (2014) 29:1349–1358
DOI 10.1007/s00467-013-2612-7
EDUCATIONAL REVIEW
Assessment of nutritional status in children with chronic
kidney disease and on dialysis
Antonio Mastrangelo & Fabio Paglialonga &
Alberto Edefonti
Received: 23 April 2012 / Revised: 6 August 2013 / Accepted: 7 August 2013 / Published online: 5 September 2013
# IPNA 2013
Abstract Protein-energy wasting (PEW) is defined as a state of
decreased body protein mass and fuel reserves (body protein and
fat mass) and is a common complication of chronic kidney
disease (CKD). It is multifactorial: the main causative factors
are hormonal imbalances and a low nutrient intake, but low
residual renal function, inadequate dialysis dose, chronic inflam-
mation and metabolic acidosis are other important contributory
factors. Adult PEW has been defined, but there is no accepted
definition of pediatric PEW and consequently no precise diag-
nostic criteria. Assessing nutritional status in children is also
complicated by the absence of a gold standard, specific abnor-
malities in body composition, and the slowly progressive course
of the disease. The evaluation of PEW should take into account
all of its pathogenetic aspects, which include dietary assessment,
clinical and anthropometric assessment (based on weight, height,
and body mass index), a panel of biochemical parameters, and a
normalized protein catabolic rate (in the case of adolescents on
hemodialysis). Bioimpedance indices can be used in individual
patients on a regular basis in centers with expertise. The longitu-
dinal follow-up data relating to the above parameters are valuable
for comparing patient and normative data. Given the complex
nature of PEW, only a multidisciplinary approach can provide an
accurate assessment of nutritional status and its derangements in
children with CKD and on dialysis.
Keywords Protein-energy wasting . Chronic kidney disease .
Nutritional status . Malnutrition . Nutritional assessment
A. Mastrangelo : F. Paglialonga (*) : A. Edefonti
Pediatric Nephrology and Dialysis Unit, Fondazione IRCCS Ca’
Granda Ospedale Maggiore Policlinico, Milan, Italy
e-mail: fabiopaglialonga@alice.it
Introduction
According to an expert panel of the International Society of
Renal Nutrition and Metabolism (ISRNM), protein-energy
wasting (PEW) in adults is defined as a state of decreased body
protein mass and fuel reserves (body protein and fat mass) [1].
PEW is a well-known complication of chronic kidney
disease (CKD) in adults and children, but its prevalence is
difficult to ascertain [2–4]. Studies of children with CKD that
have been published to date contain conflicting data, mainly
due to the use of different definitions and diagnostic criteria;
consequently, the published prevalence rates range from 6 to
65 % [3, 5–7].
One problem underlying the definition of PEW is the fact
that it is a multifactorial disease and thus very different from
true malnutrition caused by a low nutritional intake alone [4,
8, 9]. In the past, the word “malnutrition” was used as a
synonym of “protein-energy wasting” and “cachexia” in chil-
dren with CKD, but recent evidence indicates that it should be
reserved for the condition caused by inadequate nutritional
intake alone. In CKD, many factors other than inadequate
nutrient intake (such as hormonal imbalance) contribute to
PEW, which is ultimately characterized by maladaptive re-
sponses, such as an increased metabolic rate, low serum
albumin levels, and the loss of body weight. This scenario
conflicts with the definition of true “malnutrition” which, as it
is only caused by inadequate food intake, is generally easily
reversed by altering the composition of the diet. However,
merely increasing dietary intake would not cure PEW in
patients with CKD. Finally, the word “cachexia” should be
used to define the severe form of PEW that, in adults, is
characterized by serious physiological, metabolic, psycholog-
ical, and immunological complications [1].
Consequently, the nutritional assessment of children with
CKD should take into account all of the pathogenetic aspects
of PEW—and not just dietary intake [4, 10–12]. Panels of
1350
nutritional markers are required to diagnose PEW, and there is
no ideal marker that is accurate, widely applicable, easy to
interpret, and inexpensive. A group of markers, with their cut-
off values, have been identified as tools for diagnosing PEW
in adult patients with CKD, but there are no such precise
criteria for children and no accepted definition of PEW suit-
able for the pediatric population.
What makes diagnosis even more difficult is that PEW is
usually a slowly progressive process that starts with the activa-
tion of a number of catabolic pathways in an apparently well-
nourished child and then progresses to the mild depletion of
body protein and stores. It is only towards the end of the disease
process that clinical signs and symptoms appear, nutritional
markers are significantly modified, and there is a significant
increase in morbidity and mortality [10].
The assessment of nutritional status in children is also
complicated by the specific characteristics of pediatric patients
with CKD and their specific body composition abnormalities
because a decrease in muscle mass could be hidden by an
increase in fat mass and/or body water with stable or even
increased body weight [13, 14].
The aims of this article are: (1) to review both the main
factors responsible for PEW/cachexia and the relevant
markers of nutritional status and (2) to assess the value of
these factors/markers as tools for diagnosing PEW in children
with CKD and on dialysis.
Factors causing PEW
Hormonal factors
Recent studies have clearly shown that uremic hormonal
imbalances are the main cause of poor appetite in patients
with CKD. In particular, uremia leads to a reduction in
orexigenic hormones, such as acyl ghrelin, neuropeptide Y
(NPY) and agouti-related peptide (AgRP), and the accumula-
tion of anorexigenic substances, such as desacyl ghrelin,
obestatin, adiponectin, leptin, peptide YY, and visfatin
[15–20].
In healthy people, ghrelin is a hormone produced in the
gastrointestinal tract that circulates in three different forms: acyl
ghrelin, desacyl ghrelin, and obestatin. Acyl ghrelin has
orexigenic activity: it increases food intake in humans and
animals [21, 22] and promotes adiposity in rats and mice [22].
Acyl ghrelin promotes the secretion of NPY and AgRP, which
are active appetite-stimulating neuropeptides in the hypothala-
mus [23]. Ghrelin also has some cardiovascular and anti-
inflammatory effects and reduces oxidative stress [24–26].
The other two circulating forms of ghrelin, together with the
hormone leptin, are anorexigenic and antagonize the central
effects of acyl ghrelin; leptin additionally has a pro-
inflammatory effect and reduces food intake [23].
Pediatr Nephrol (2014) 29:1349–1358
The peptide cholecystokinin (CCK) is a widespread gut
hormone that has a number of physiological effects, including
the stimulation of gallbladder contraction and pancreatic and
gastric acid secretion, the slowing of gastric emptying, and the
suppression of energy intake [27]. CCK is released in re-
sponse to food intake and induces satiety through the CCK-
A receptors on vagal afferents [27].
All of these hormones are mainly degraded by the kidneys
[23]. CKD patients have high serum levels of desacyl ghrelin,
leptin, and obestatin due to reduced renal clearance, whereas
their serum acyl ghrelin levels are low [18, 28]. As it has been
demonstrated that there is no increase in the production of
total ghrelin, the higher serum levels are considered to be
mainly caused by the reduced renal degradation [29].
In 2010, Büscher et al. [18] found higher levels of total
ghrelin in pediatric CKD and dialysis patients than in controls
and transplant recipients. There was no between-group differ-
ence in acyl ghrelin, but the levels of obestatin and desacyl
ghrelin were higher, leading the authors to suggest that re-
duced anabolism may be part of a protective strategy of the
uremic organism, which tries to reduce metabolic processes in
order to inhibit the accumulation of toxic metabolites normal-
ly cleared through the kidneys [18].
High plasma CCK levels have been negatively associated
with nutritional status in CKD/dialysis patients. The chronic
administration of CCK reduces meal size, but does not affect
any overall change in daily caloric intake or body weight because
of a compensatory increase in the number of meals [27].
The imbalance between orexigenic and anorexigenic sub-
stances is probably responsible for anorexia and PEW in chil-
dren with CKD [4, 30]. However, as these indices are currently
available only for research purposes, we can only rely on their
effects on nutrient intake.
Decreased nutrient intake
A number of (mainly crossover) studies of adults and children
with CKD have found a significant correlation between glo-
merular filtration rate (GFR) and dietary energy and protein
intake [31, 32] and concluded that reduced energy intake for
age appears even in the early stages of CKD [31]. However,
other studies have found that children with CKD have a
normal energy intake in relation to their body size [33], and
it has been repeatedly demonstrated that protein intake is
normal or high even in patients with severe CKD [34].
The parents of children with CKD sometimes report altered
taste, a furrowed tongue, yellowish teeth, pale/bronze skin,
nausea, vomiting, and food refusal which, particularly in
infants, may easily lead to a reduction in dietary intake [35].
An underlying and treatable cause can be identified in some
cases, including gastroesophageal reflux and unpalatable
medications. Infancy and early childhood are the most
nutrition-sensitive phases of growth, when dietary intake is
Pediatr Nephrol (2014) 29:1349–1358
associated with a greater risk of protein wasting and impaired
physical development.
Factors contributing to the development of PEW
Low residual renal function and dialysis dose
Residual renal function and an adequate dialysis dose have
been found to have a positive effect on dietary intake and
nutritional parameters in adults and children undergoing
chronic dialysis [31, 36–38]. In terms of residual renal func-
tion, Norman et al. found that children with severe CKD had
lower anthropometric indices [weight, height, and body mass
index (BMI)] than those with a mild reduction in GFR and
that, similarly, mean total energy intake was higher in “nor-
mal” children than in those with severe chronic renal insuffi-
ciency [31]. In pediatric patients treated with hemodialysis
(HD), Guzzo et al. found a close correlation between residual
Kt/V and the normalized protein catabolic rate (nPCR, an
index of protein intake), with significantly higher nPCR
values in patients with residual renal function than in those
without [36].
In terms of the dialysis dose, a positive correlation between
dialytic creatinine clearance and growth was first demonstrat-
ed by Schaefer et al. [37] and then confirmed by Tom et al.
[39]. More recently, Fischbach et al. have shown that daily on-
line hemodiafiltration has a beneficial effect on growth and
dietary protein intake (DPI) [38].
Taken together, these findings could be due to better con-
trol over uremic toxicity or the positive effects on food intake
of maintaining water excretion and a less protein-restricted
diet. However, regardless of the biological mechanism, pa-
tients with no residual renal function and those receiving an
inadequate dialysis dose are at greatest risk of low dietary
intake, reduced growth, and impaired nutritional status, which
is why the indices of residual renal function (such as creatinine
clearance) and dialysis adequacy [such as Kt/V for urea and
total creatinine clearance in children on peritoneal dialysis
(PD)] should be regularly monitored.
Inflammation
Many studies of adult CKD patients have found a high preva-
lence of inflammation and a close correlation between inflam-
mation, “malnutrition,” and cardiovascular complications, and
these findings have led to the identification of what is known as
the malnutrition-inflammation-atherosclerosis syndrome [40].
Recent studies have clarified the mechanisms linking inflam-
mation and muscle wasting: among others, uncontrolled acti-
vation of the ATP-dependent ubiquitin–proteasome system is
the main cause of muscle protein degradation in the case of a
pro-inflammatory uremic milieu [8, 9].
1351
Only a few studies have investigated inflammation in chil-
dren, and the results of these are less striking and more contra-
dictory [7, 41–44]. Sylvestre et al. studied 64 children with
CKD and found that the prevalence of inflammation [diagnosed
on the basis of C-reactive protein (CRP) levels of >1 mg/L]
ranged from 22 % among patients on PD to 40 % among those
on HD [7]. Goldstein et al. measured serum cytokine concen-
trations in seven children on HD and seven on continuous
cycling PD and found that the serum concentrations of the
pro-inflammatory cytokines interleukin-1beta (IL-1β), IL-6,
IL-8, and tumor necrosis factor-alpha were significantly high,
whereas those of anti-inflammatory cytokines IL-4 and IL-10
were normal [42]. Foster et al. found that CRP levels were
higher in patients with CKD stage 4 and 5 and during dialysis
than in those with CKD stage 2 and 3. Similarly, IL-6 levels
were higher in the patients on dialysis than in those with CKD
stage 2 and 3. However, there was no significant association
between CRP and leg muscle deficits.
It is worth remembering that the hypothalamus is sensitive
to a series of hormonal stimuli, such as those cited in para-
graph 1.1, but also to cytokines: high serum cytokine levels
act through the hypothalamus to reduce appetite and increase
the sense of satiety, presumably because hormonal receptors
(e.g. leptin receptors) have some homology with cytokine
receptors (e.g. IL-6 receptors) [27, 45].
Metabolic acidosis
Metabolic acidosis is common in patients with CKD and is
associated with a number of complications, including in-
creased muscle wasting and reduced albumin synthesis [8, 9,
46, 47]. In particular, this condition can increase the transcrip-
tion of genes encoding proteins of the ATP-dependent
ubiquitin–proteasome pathway, thus increasing the activity
of the ATP-dependent ubiquitin–proteasome system and lead-
ing to muscle protein degradation [47]. It has been shown that
correcting acidosis improves protein balance and muscle mass
[46]. Similarly, the risk of hypoalbuminemia is significantly
higher in CKD patients with acidosis than in those with a
normal acid/base balance, which suggests that acidosis plays a
role in reducing albumin synthesis [46]. However, it should be
remembered that acid/base status depends on many factors,
including primary renal disease, dietary intake, residual kid-
ney function and dialysis modality and dose.
Birth history
It is well-known that birth history has a significant influence
on adult height in the general population. In particular, the
childhood and adult height of children born small for their
gestational age (SGA) is >2 standard deviations (SD) below
the mean [48]. The effects of low birth weight (LBW), pre-
maturity, SGA, and intensive care unit stay was studied by
1352
Greenbaum et al. in a large cohort of children and adolescents
with mild or moderate CKD. These authors found that the
children born with a LBW or SGA were shorter than those
whose birth weight was >2,500 g or who had a birth weight of
>10th percentile for their gestational age, thus suggesting that
LBW and SGA should be considered as risk factors for short
stature in children with CKD [49].
These findings may be explained by the negative effect of
CKD on normal catch-up growth among children who are
SGA or LBW, and the fact that the more severe the congenital
CKD, the higher the incidence of SGA or LBW due to
underlying kidney disease.
Additional risk factors for PEW
The following additional risk factors cannot be considered to
be at the same level of importance as the causative and
contributory factors, but they have been frequently associated
with a higher incidence of PEW. They include patient factors,
such as a young age, a young age at the onset of end-stage
renal disease (ESRD), high dialysis vintage and poor compli-
ance due to psychosocial problems, medications (such as
prolonged corticosteroid treatment), proteinuric primary kid-
ney diseases, and the presence of co-morbidities, such as
congenital cardiac diseases, neurological disabilities, or mal-
formation syndromes [3, 50]. As these co-morbidities are
quite different from those frequently observed in adult patients
(mainly tumors, diabetes mellitus, and acquired cardiovascu-
lar diseases), it is necessary to collect further data on the
associations between them and the nutritional status of chil-
dren with CKD.
Children on PD experience significant losses of amino
acids and proteins in the effluent dialysate. Protein losses are
relatively higher in children than in adults, with infants
experiencing the greatest losses per kilogram of body weight
[51]. As proof of this, the Kidney Disease Outcomes Quality
Initiative (KDOQI) guidelines recommend a higher DPI for
pediatric PD patients than for those with CKD stages 4–5 and
those with CKD stage 5 on HD [52].
Evaluation of PEW
Dietary assessment
Any comprehensive evaluation of a CKD patient must include
a quantitative estimate of dietary intake by means of a dietary
interview or a dietary diary, or the calculation of the nPCR in
patients on HD [52].
The most widely used methods of evaluating dietary intake
in children with CKD are three 24-h dietary recalls in adoles-
cents or 3-day dietary diaries (preferable in children aged
Pediatr Nephrol (2014) 29:1349–1358
<10 years), which make it possible to calculate the daily intake
of calories and macronutrients (protein, carbohydrates, fat),
vitamins, and minerals. However, one major drawback of
these methods is their dependence on the compliance of
parents and patients in compiling the diary, and the parents’
reliability [52].
The recently updated pediatric National Kidney Founda-
tion (NKF) KDOQI nutritional guidelines (Table 1) recom-
mend using dietary intake indices to evaluate the nutritional
status of children with CKD [52].
Given the importance and complexity of dietary assess-
ment, every Pediatric Nephrology Unit caring for children
with CKD should have a full- or part-time specialized dieti-
cian on its staff.
Clinical assessment
Children with cachexia complain of a number of symptoms,
particularly asthenia and difficulties in pursuing their daily
activities. Common gastrointestinal symptoms consist of an-
orexia, nausea, vomiting, and constipation. Other clinical
signs of cachexia include impaired teeth, hair, tongue, skin,
and nails, as well as muscle atrophy and decreased subcuta-
neous fat. At this stage, complications can occur, such as
recurrent infections, an increased need for hospitalization,
and major alterations in all of the biochemical and anthropo-
metric parameters.
Anthropometric parameters
In addition to dietary intake and nPCR (for adolescents on
HD), the recently updated pediatric NKF KDOQI nutritional
guidelines (Table 1) recommend anthropometric indices [52].
These consist of the height (or length)-for-age percentile or
SD score (SDS), the height (or length) velocity-for-age per-
centile or SDS, estimated dry weight and the weight-for-age
percentile or SDS, the BMI-for-height/age percentile or SDS,
Table 1 Recommended parameters for the nutritional assessment of
children with chronic kidney disease according to the National Kidney
Foundation Kidney Disease Outcomes Quality Initiative guidelines
Dietary intake
Height or length-for-age percentile or SDS
Height or length velocity-for-age percentile or SDS
Estimated dry weight and weight-for-age percentile or SDS
BMI-for-height/age percentile or SDS
Head circumference-for-age percentile or SDS (for children aged
<3 years)
nPCR (for adolescents on hemodialysis only)
SDS, Standard deviation score; BMI, body mass index; nPCR, normal-
ized protein catabolic rate
Pediatr Nephrol (2014) 29:1349–1358
and the head circumference-for-age percentile or SDS (up to
36 months of age).
The importance of anthropometric markers is underlined
by their close association with mortality, which has also been
clearly demonstrated in pediatric CKD patients [53, 54]. A 7-
year survey of the US Renal Data System database of 1,949
children with ESRD showed that the adjusted risk of mortality
increased by 14 % for each 1 SDS decrease in height, and by
12 % for each 1 SDS decrease in growth velocity—regardless
of the type of treatment (HD, PD, transplantation) [53]. Sim-
ilarly, a study of 2,306 patients enrolled in the North American
Pediatric Renal Transplant Cooperative Study, who were aged
<21 years at the time they started dialysis, demonstrated that
children with a height of ≤−3 SDS were at greater risk of death
(risk ratio 2.9) than those whose height was normal [54]. Poor
growth is therefore a marker of the severity of CKD and the
quality of care and has been identified as being central to the
diagnosis of PEW [53, 54]. However, as height is also
influenced by other aspects of CKD, such as metabolic bone
disease and growth hormone abnormalities, height is not
entirely a nutritional marker.
In adults, an unintentional weight loss or reduction in weight
of >5 % over a 3-month period or >10 % over a 6-month period
is suggested as an indicator of PEW [1]. A U-shaped associa-
tion between BMI and mortality has been found in children
with CKD stage 5, with a 6 % greater risk of mortality for each
1 SD unit difference [53]: in other words, both under- and over-
nutrition are associated with poor outcomes.
However, there are some reservations concerning anthro-
pometric indices. First of all, the choice of the reference
population is often problematic because there are significant
differences between one growth chart and another that can
sometimes make the diagnosis of delayed growth unclear. The
Centers of Disease Control and Prevention (CDC) published
revised North American growth reference charts for infants
and children up to 20 years of age in 2000, and the World
Health Organization (WHO) released new growth standards
for children from birth to 5 years of age in 2006 [52]. Bonthuis
et al. have recently studied 18 unique national height-for-age
charts from 28 European countries via the ESPN/ERA-EDTA
registry and compared these with charts from the WHO, Euro-
Growth reference, and CDC [55]. These authors advocate
using recent national or European height-for-age charts when
monitoring the growth of healthy and diseased European
children. For a world-wide perspective, WHO charts have
long been used in most countries for children up to 5 years
of age, and the NKF/KDOQI guidelines recommend using
them from birth to 2 years of age because they represent ideal
growth [52]. However, whichever growth charts are used, the
most important factor is regular surveillance and intervention
if growth falters.
Secondly, according to the KDOQI guidelines, the severe
growth deficit of some patients with CKD means that
1353
normalization by height and age is necessary (at least for
BMI). In such cases, it is recommended that nutritional intake
by height rather than by chronological age be recorded [52].
Thirdly, abnormalities in the body composition of uremic
patients (total body water, and lean and fat mass) are major
confounding factors: Rashid et al. studied BMI in 50 children
with chronic renal failure and 50 pediatric kidney transplant
recipients, and found that their BMI SDS (standardized for
height and age) was significantly lower than their fat mass
SDS and higher than lean mass SDS as calculated by means of
dual-energy X-ray absorptiometry (DXA) [14]. These authors
concluded that children with CKD have a discordant body
composition characterized by a low lean mass and relatively
high fat mass that cannot be identified by BMI [14].
Other anthropometric parameters that are not recommend-
ed by the KDOQI guidelines but may be useful in some cases
are tricipital skin-fold thickness and mid-arm circumference,
as well as their calculated derivatives, namely, mid-arm mus-
cle circumference (MAMC), arm muscle area (AMA), and
arm fat area [52].
There are a number of reasons why mid-arm anthropome-
try is no longer recommended by the KDOQI guidelines.
First, reliable measurements are difficult to obtain because
they are extremely operator dependent and lack precision,
with intra- and inter-observer coefficients of variation of 3–7
and 8–20 %, respectively. Moreover, it is not clear whether
MAMC and AMA accurately reflect total muscle mass in
children with CKD, and abnormalities in these parameters
have never been convincingly described. Finally, only a few
studies have investigated the relationship between mid-arm
anthropometry and outcomes [52]. Despite this, the 2006
expert panel of the ISRNM included MAMC among the
criteria for diagnosing PEW in adults with CKD [1]. On the
basis of this recommendation, although the indices derived
from skin-fold thickness and arm circumference are not rec-
ommended for the routine assessment of nutritional status by
the pediatric KDOQI guidelines, they can be used by centers
with extensive experience of making such measurements,
preferably by the same member of staff.
Biochemical parameters
Various biochemical parameters have been proposed as
markers of nutritional status, including serum albumin and
total protein, pre-albumin, transferrin and creatinine levels,
hemoglobin, total lymphocyte counts, cholesterol, triglycer-
ides, and retinol binding protein. However, although all of
these may contribute to a comprehensive nutritional assess-
ment, none of them can be considered to be sensitive or
specific enough to be used at diagnostic markers for PEW.
Nevertheless, serum albumin and serum creatinine (for
patients on dialysis only) have historically received particular
attention. Serum albumin has been extensively studied,
1354
particularly in adults with CKD, but there is indisputable
evidence against its use as a pure marker of nutritional status
[56–58]: (1) not even severe protein and calorie restriction
leads to a decrease in serum albumin levels; (2) most nutri-
tional interventions have no effect on serum albumin levels
and, in particular, no improvement was observed in a study of
hemodialyzed adolescents undergoing intra-dialytic parenter-
al nutrition [59]; (3) a study of 44 pediatric patients on HD
found no correlation between serum albumin and weight loss
[58]. However, a striking association has been found between
serum albumin levels and mortality in both adults and children
with CKD [56, 60]: Wong found a 54 % higher risk of death
for each 1 g/dL decrease in serum albumin 45 days before the
start of dialysis [60], and studies of adult patients with CKD
have found a close association between serum albumin levels
and factors other than nutrition, such as chronic inflammation
[56] and an increase in fluid overload.
Taken together, these findings suggest that, although serum
albumin may be considered a poor marker of nutrition per se,
it may be a very useful marker of disease severity [57]. It is for
this reason that the 2006 ISRNM panel indicated low serum
albumin levels as one of the criteria required to diagnose the
complex clinical picture of PEW in adults [1]. The presence of
low serum albumin levels should suggest a further evaluation
of nutritional status also in children with CKD or on dialysis,
unless it is caused by nephrotic proteinuria.
Given its shorter half-life (2 vs. 20 days of albumin), serum
pre-albumin has been proposed as an alternative marker of
PEW and is included in the list of parameters recommended
by the ISRNM [1]. However, it has a number of important
limitations, such as its dependence on renal clearance and
recent protein intake. Moreover, no pediatric data have yet
been published.
Pre-dialysis serum creatinine levels have been used as a
surrogate marker of muscle mass in patients on chronic dial-
ysis and, although they may be affected by the dialysis dose, it
has been shown that they closely correlate with some proxies
of nutritional status [3]. However, a recent study of 81 patients
on maintenance HD showed that the inter-dialytic increase in
serum creatinine levels provided little additional information
about nutritional status or the risk of mortality [61].
The nPCR is derived from the inter-dialytic increase in
blood urea nitrogen levels and can be calculated as the differ-
ence between the level at the end of one HD session and that at
the beginning of the next [52, 62, 63]. Some interesting
pediatric studies have shown that nPCR correlates well with
DPI and residual renal function and that an increase in nPCR
can be obtained by means of intra-dialytic parenteral nutrition
[36, 59]. More importantly, low nPCR levels predict weight
loss in adolescents on HD, with a fourfold higher risk in
patients with an nPCR of <1 g/kg than in those with an nPCR
of >1 g/kg [58]. According to the NKF KDOQI guidelines,
nPCR should be measured monthly in adolescents on
Pediatr Nephrol (2014) 29:1349–1358
maintenance HD [52], but it cannot replace dietary history
as it does not provide information on energy intake.
Prospective studies of urea and nitrogen output in adults
undergoing PD have led to the extrapolation of qualitative
relationships that allow an assessment of DPI when only the
appearance of urea is known [64]. The reasons for this are the
correlations between DPI with total nitrogen appearance
(TNA), non-protein nitrogen appearance (nPNA), and urea
protein appearance (UNA), and the correlations between
UNA and TNA and nPNA. These clinically useful relation-
ships have been studied in children on PD [65], and it has been
found that the relationship between UNA and TNA is age-
dependent and specific to pediatric PD patients.
Finally, inflammatory indices cannot be considered clear
markers of PEW in children with CKD and were not included
among the diagnostic criteria in the NKF KDOQI guidelines.
However, given the high prevalence of inflammation in published
pediatric series and its negative impact on prognosis, periodic
monitoring of highly sensitive CRP is suggested for children on
dialysis; other inflammatory markers (e.g. pro-inflammatory cyto-
kines) should only be used for research purposes.
Bioelectric impedance analysis and bioimpedance
spectroscopy
Single- and multi-frequency bioelectric impedance analysis
(BIA) and bioimpedance spectroscopy (BIS) have both been
proposed as means of assessing body composition in various
populations, including children and adults with CKD [5, 66,
67]. There are various interpretative models (such as vectorial
analysis), and many predictive equations have been designed
to estimate body compartments (lean body mass and fat mass)
quantitatively or semi-quantitatively, but there is still no clear
evidence in favor of using BIA or BIS in clinical practice. One
of the main drawbacks of BIA is its inaccuracy in the presence
of abnormalities in body fluid distribution: i.e., it shows a poor
sensitivity to changes in fluid volume in the trunk compared
with the limbs, where the measurements are made. BIA esti-
mates of body compartments have been extensively used in
stable healthy populations, with results similar to those
obtained using hydrodensitometry and total body potassium;
however, in dialysis patients, the accuracy of these estimates is
contingent on stable hydration, which is difficult to obtain in
many cases. The few published data on the use of BIA in
children have far from demonstrated its real usefulness in
identifying patients with PEW, and the recent major guidelines
do not recommend it as an essential means of assessing
nutritional status in CKD patients.
However, in centers with extensive experience of the meth-
od, BIA can be useful when used on a regular and longitudinal
basis [5, 68, 69] because the indices of resistance and reac-
tance are very sensitive in detecting changes in hydration in
individual patients; however, comparing theses indices (and,
Pediatr Nephrol (2014) 29:1349–1358
even more, the data coming from the predictive equations)
with the available reference values could be misleading.
Other markers
It has been shown that DXA reliably predicts fat and lean
mass in children and adults. In a recent study, Foster et al.
used DXA to determine whole body and regional lean and fat
mass in 143 children with CKD and 958 controls; the results
clearly showed that CKD is associated with leg lean mass
deficit, greater trunk lean mass and fat mass, variable whole
body lean mass, and normal leg fat mass [44]. Unfortunately,
DXA is expensive and difficult to repeat in the follow-up of
children with CKD.
Combined scores such as the “Subjective Global Assess-
ment” (SGA) and the “Malnutrition Inflammation Score”
have been used to assess nutritional status in adults with
CKD, but there is still no pediatric equivalent to these scores
[70, 71]. The Anthropometry-BIA Nutrition score [72] has
been proposed in the pediatric setting, but its accuracy has not
been clearly demonstrated.
Nutritional approach to children with CKD
and on dialysis
The parameters recommended by the NKF KDOQI guide-
lines for the assessment of nutritional status in children with
CKD [52] are the indices of dietary intake, anthropometric
indices, and nPCR (only for adolescents on HD), and the
frequency of nutritional assessment depends mainly on the
age of the child (small children need more frequent monitor-
ing) [52]. These parameters are included in our own nutrition-
al approach to children with CKD and on dialysis, which is
summarized in Table 2 and includes some key concepts. First
of all, the complex and multidisciplinary assessment of nutri-
tional status requires not only clinicians, but also skilled
dieticians, specialized nurses, and (in order to provide insight
and support where needed), psychologists, and social workers.
Secondly, both the sensitivity and specificity of these nutri-
tional parameters are greatly influenced by the particular
characteristics of children with CKD and abnormalities in
their body composition, which should be carefully considered
when the data are interpreted. Thirdly, consistent and frequent
assessment of nutritional status is needed, particularly in small
children. Longitudinal follow-up data add value to the neces-
sary comparison of patient and normative data: progressive
alterations in one or more parameters should lead to a review
of the factors contributing to PEW and the additional risk
factors for PEW in order to identify possible changes, as well
as to the closer monitoring of nutritional parameters.
The many uncertainties that remain are due to the lack of
specific pediatric data. Most of the current recommendations
1355
Table 2 Nutritional approach to children with chronic kidney disease
1. Assessment and monitoring by a multidisciplinary team of the factors
contributory to PEW
-Low dietary intake (protein, energy, vitamins, and minerals)
-Decreasing residual renal function
-Low dialysis dose
-Chronic inflammation
-Acidosis
2. Assessment and monitoring of additional risk factors for PEW
-Young age
-Primary proteinuric renal disease
-Associated comorbidities
-High dialysis vintage
-Psychosocial factors (low adherence)
3. Consistent and frequent assessment of the nutritional status
-Clinical assessment
-Anthropometric parameters
-Biochemical markers (including nPCR)
-Bioimpedance analysis and spectroscopya (longitudinal measures)
4. If any progressive alteration of a nutritional parameter is detected:
-Reassess the factors listed in points 1 and 2 for possible changes
-Increase frequency of nutritional assessments
PEW, Protein energy wasting; nPCR, normalized protein catabolic rate
a
At centers with extensive experience of such measurements
are based on adult studies, but adult and pediatric patients are
very different in terms of pathophysiology, contributory and
additional risk factors, and morbidity. Large, well-designed
studies are urgently needed to define the real usefulness of the
available diagnostic methods and determine the optimal diag-
nostic criteria for PEW in pediatric patients with CKD.
Questions (answers are provided after the reference list)
1. Which of the following factors is not a risk factor for PEW
in children with CKD?
a. Young age at onset of end-stage renal disease
b. Polyuria
c. Proteinuric kidney disease
d. Poor compliance
2. Which of the following hormones does not cause anorexia
in CKD?
a. Desacyl ghrelin
b. Obestatin
c. Neuropeptide Y
d. Acyl ghrelin
1356
3. Which of the following parameters is recommended by
the NKF KDOQI guidelines for the assessment of nutri-
tional status in children with CKD?
a. Serum albumin
b. Mid-arm muscle circumference
c. BMI-for-height/age percentile or SDS
d. BMI-for-age percentile or SDS
4. Which of the following biochemical parameters has not
been proposed as a nutritional parameter?
a. Total lymphocyte count
b. Serum Immunoglobulins
c. Serum pre-albumin
d. Serum creatinine
5. Which of the following factors has to be considered
causative of PEW in children with CKD?
a. Chronic inflammation
b. Low dialysis dose
c. Metabolic acidosis
d. Hormonal factors
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