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490

height below the third percentile at the time of
enrollment into the study [7, 10]. The proportion
of children with a height SDS < -1.88 was higher
when GFR was lower: height SDS was <−1.88 in
31.1% of children with GFR >25 ml/min/1.73m2,
47.2% of those with GFR between 10 and 25 ml/
min/1.73m2 and 68.4% of those with GFR
<10 ml/min/1.73m2. Growth failure is also more
severe at younger ages: the average height SDS
in infants aged 0–1  years at registry entry was
−2.30 and in young children between 2 and
5  years was −1.69, whereas in adolescents
(>12  years), it was −0.96 [7]. Additionally,
infants born with CKD were found to have lower
height SDS compared to those with acquired diseases [7, 11]. Infancy is a particularly high-risk
interval given that one third of total postnatal
growth occurs during this period [12].
Inadequate calorie intake is one among many
factors contributing to growth failure in CKD and
is the dominant contributor in infants and very
young children [8, 13–15]. Anorexia is common
[13–15]; a number of factors may lead to anorexia
including gastroesophageal reflux, delayed gastric emptying, altered taste, and increased levels
of cytokines such as leptin, IL-1, IL-6, and TNF-α
[14, 16–19]. Disruption in the levels of appetite-­
regulating hormones such as leptin and ghrelin
leads to both a lack of appetite and early satiety
[14, 18–21]. Other reasons for inadequate intake
include fluid and dietary restrictions and frequent

vomiting [22, 23]. Children with polyuric CKD
may favor water consumption over intake of
food. Those on PD may have diminished appetite
due to a sense of abdominal fullness.
While nutrition is important throughout
childhood, the contribution of nutritional intake
to growth depends heavily on the phase of
growth [24–26]. Normal postnatal growth can
be divided into infantile, childhood, and pubertal phases. Growth during the infantile phase is
driven primarily by nutritional intake. Therefore,
inadequate intake in infancy manifests with
growth failure. Routine calorie supplementation
in infants with CKD has been shown to improve
growth [27–30]. Healthy infants transition from
the infantile to the childhood growth phase
between 6 and 12 months. However, the child-

B. J. Foster and A. Tsampalieros

hood phase may be delayed until 2–3  years in
children with CKD [14, 31]. During the childhood phase, growth depends mainly on growth
hormone. The pubertal phase of growth, which
in CKD is often delayed and of shorter duration
than normal [32, 33], is driven by both growth
hormone and sex hormone [13, 34]. Outside
infancy, energy intake among children with
CKD is usually appropriate relative to body size
[2, 35]; there is no good evidence that nutritional supplements enhance growth in older
children.
Weight loss is another important indication for

nutritional supplementation in children with
CKD [2]. Wasting, defined as low weight-for-­
height, was initially thought to be due exclusively
to inadequate nutritional intake or malnutrition
[36, 37]. However, there is now evidence that
other factors such as systemic inflammation,
abnormal neuropeptide signaling, and endocrine
perturbations may contribute to wasting in the
context of CKD [36, 38, 39]. Children with
cachexia/wasting syndrome may have an
increased metabolic rate or anorexia with altered
body composition (reduced muscle mass and
body weight, with normal or increased fat mass);
therefore, increasing food consumption or altering the diet may not help children with cachexia.
In contrast, malnutrition can be corrected by supplying more food or improving the diet [36, 40].
Neurocognitive dysfunction, including memory deficits, academic difficulties, and deficits in
executive functioning, may also be a consequence
of CKD and ESRD [41–44]. Because infancy is a
period of rapid neurodevelopment, infants are at
greatest risk for neurodevelopmental disorders.
Earlier reports [45–48] found developmental
delay in up to 60–85% of infants with severe
renal insufficiency. However, these reports predate recognition of the roles of aluminum exposure and malnutrition in neurodevelopmental
disturbances. Subsequent small observational
studies showed superior developmental outcomes
associated with early intervention including
aggressive nutrition and dialysis [48, 49].
Nutritional intervention has the potential to have
an important positive impact on neurodevelopment during infancy [14].

27  Controlled Enteral and Parenteral Nutrition in Children on Dialysis

Indications for Supplemental
Nutritional Support
The 2008 Kidney Disease Outcomes Quality
Initiatives (KDOQI) nutrition guidelines recommend: Supplemental nutritional support should
be considered when the usual intake of a child
with CKD stages 2–5 or 5D fails to meet his or
her energy requirements and the child is not
achieving expected rates of weight gain and/or
growth for age. (Evidence Grade B) Oral intake
of an energy-dense diet and commercial nutritional supplements should be considered the preferred route for supplemental nutritional support
for children with CKD stages 2–5 and 5D.
(Evidence Grade B) When energy requirements
cannot be met with oral supplementation, tube
feeding should be considered [2] (Evidence
Grade B).
It is important to remember that a normal rate
of weight gain for age depends on a normal rate
of linear growth. Outside infancy, a child with
growth failure should not be subjected to a long
trial of nutritional support before starting growth
hormone therapy.

Indications for Tube Feeding
Most infants and toddlers with moderate to
severe CKD show substantially decreased spontaneous oral intake [50, 51], and the majority
require tube feeding. Dietary intake should be
regularly monitored in infants and toddlers with

CKD.  Tube feeding should be considered for
children unable to meet their estimated energy
requirements (EER) orally who are either underweight, are growth restricted (weight-for-age or
length-for-­height SDS less than −1.88), or are
failing to maintain normal weight gain or growth
[2]. Early intervention, with a goal of preventing
growth retardation, is a key principle of nutritional management in infants and toddlers with
CKD.  Height potential lost during infancy is
extremely difficult to catch up later, and even
short periods of poor growth during infancy may
result in substantial loss of height potential.
Evidence of stunting is not required to justify

491

intervention. Greater final height is achieved in
children in whom tube feedings are started
before important height deficits are noted [52].
Catch-up growth is most likely during infancy
[13]. The goal of tube feeding is to ensure intake
of at least 100% of the EER; greater energy
intake is required for catch-up growth. This may
be challenging especially for those who have
volume restrictions, delayed gastric emptying,
frequent emesis, or gastroesophageal reflux [5].
Tube feeding is rarely required for older children with CKD, in whom intakes are usually
normal relative to body size [35]. It is possible
that poor intake is a consequence of the poor
growth, rather than the cause. A study of 33
children with CKD showed an almost 12%

increase in spontaneous calorie intake during
treatment with recombinant human growth hormone [53]. Older children with CKD should
have dietary intake monitored regularly [2]. If
intake is found to be inadequate, an underlying
reason should be sought. Causes of poor nutritional intake among older children include progressive uremia, gastrointestinal disorders, and
eating disorders. Progressive uremia may
require initiation or intensification of dialysis
[54]. Growth hormone therapy may promote
greater oral intake by stimulating metabolic
demand. If nutritional supplements are deemed
necessary, the oral route should be the first
choice. Tube feedings should be limited to children with progressive weight loss or growth
failure who are unable to take adequate calories
orally [2].

 vidence for Benefits of Tube
E
Feeding: Infants
The literature on tube feeding in children with
CKD is difficult to interpret. There have been
no randomized trials assessing the impact of
tube feeding on growth or other outcomes. In
addition, confounding factors including severity of CKD, type and intensity of renal replacement therapy, and age of the child  – all of
which may independently influence growth
and/or response to nutritional supplementa-


492

tion – make comparisons between studies challenging. Numerous studies of infants with

CKD showed significant increases in height
velocity following NG or gastrostomy tube
feeding [12, 27–29, 52, 55–57]. In studies
including both infants and older children,
growth benefits due to tube feeding were evident among infants when the outcomes of older
children were separated from those of infants
[29, 58, 59]. Results of studies published in
2000 onward are summarized in Table  27.1.
The largest study to date included 153 infants
under the age of 24 months maintained on peritoneal dialysis (PD), 55% of whom received
gastrostomy or NG tube feeds [12]. BMI- and
height-for-age SDS were significantly higher
in children receiving gastrostomy feeds compared to those who received NG feeds or no
tube feeding. Catch-up growth occurred only
in those receiving gastrostomy tube feeding.
Tube feeding is also an important means of
delivering sodium and fluid supplements to
infants with high urinary sodium and water losses
due to polyuric CKD [27, 28, 52], and to infants
treated with PD, who may also experience large
sodium losses through the dialysate [13]. These
high fluid volumes and large doses of sodium are
rarely taken orally. Linear growth is impaired by
a negative sodium balance [60]. Furthermore,
volume depletion due to sodium and water losses
has also been reported to result in neurologic
injury [2].
While there had been initial concerns that
children (specifically infants) who received
enteral tube feeds may have disproportionate

gains in weight compared to height [29, 58] and
thus may be predisposed to becoming overweight after having their gastrostomy removed,
a later study demonstrated otherwise. Sienna
et al. [61] found that while children with CKD
who received tube feeds for a median of
2.9 years, starting at a median age of 1.7 years,
had increases in weight- and BMI-for-age
Z-scores, these did not continue to increase significantly up to 5  years after having their gastrostomy removed.

B. J. Foster and A. Tsampalieros

 vidence for Benefits of Tube
E
Feeding: Older Children
There is no strong evidence supporting the benefit
of tube feeding in promoting growth in older children and adolescents with CKD.  Although adequate nutrition is certainly necessary to support
normal growth in older children, CKD-­related disturbances in the effects of growth hormone and in
normal puberty are more important drivers of poor
growth than inadequate nutrition in this age group
[34, 62–64]. Indeed, undernutrition is increasingly
uncommon, while obesity is a problem of increasing prevalence among older children with endstage renal disease (ESRD) [65]. A recent study of
over 4000 children and adolescents with ESRD
across 25 European countries found that 40.8% of
children 12–15  years old were overweight or
obese, while only 1.4% were underweight. In contrast, only 9% of children under 1 year of age were
overweight or obese, and 15.8% were underweight
[66].
Selected older children who are observed to
have inadequate intake and are unable to tolerate
oral supplements may benefit from supplemental

tube feeding [2]. However, this represents the
minority of older children with CKD. Therapies
with proven benefit in improving growth, such as
growth hormone [67], should not be delayed by
prolonged trials of supplemental calories.

Nasogastric (NG) Versus
Gastrostomy Tube Feeding
Home tube feeding either with a NG tube or gastrostomy has been used successfully in infants
discharged from the neonatal intensive care unit
[68] and has been found to promote growth and
decrease the length of hospital stay [68–70].
There are two methods for delivering enteral
tube feeds: nasogastric or gastrostomy.
Nasogastric tube feeding  The use of NG feeding in children with CKD began in the 1980s [71,
72]. NG tube feeding is suitable to provide nutri-


27  Controlled Enteral and Parenteral Nutrition in Children on Dialysis

493

Table 27.1  Summary of studies assessing the use of enteral feeding among children with CKD in association with
growth
Study year
published
Kari et al.
[28] 2000

Population

N = 81
Age: 0.7* (0 to
4.5) years
GFR: <20 ml/
min/1.73m2
Group 1:
Conservative
therapy: N = 25
Group 2:
Preemptive
transplant:
N = 20
Group 3:
Dialysis N = 36

Study design
Case series

Ledermann
et al. [55]
2000

N = 20
Age: 0.34 (0.02
to 1) years
All on
peritoneal
dialysis

Case series

Ellis et al.
[115] 2001

N = 137
Age: All
<6 years at the
start of dialysis
<3 months:
N = 51
3–23 months:
N = 52
2–5 years:
N = 34
Peritoneal
dialysis:
N = 126
Hemodialysis:
N = 8

Cohort study
using data from
North
American
Pediatric Renal
Transplant
Cooperative
Study

Intervention

Tube feeds:
N = 66
100% estimated
average
requirement for
calories
Conservative:
Tube feeds
N = 20
Preemptive
transplant:
Tube feeds
N = 14
Dialysis: Tube
feeds N = 32
Tube feeds:
N = 18
NG: N = 9
G-tube: N = 8
NG and G-tube:
N = 1
Two did not
receive tube feeds
Goal
RDA > 100% for
calories

Supplemental
feeds received in
N = 96

NG only: N = 52
G-tube only:
N = 27
NG and G-tube:
N = 8
NG + othera:
N = 3
Others: N = 5
The rest received
no supplemental
feeds
Did not report
caloric intake

Duration
1.9* (0.1 to 6.8)
years

Outcome
The study demonstrated
catch-up growth among
infants and young
children treated with
tube feeding

Follow up 1 and
2 years from the
start of
peritoneal
dialysis

Mean height-for-age
SDS at the start was
−1.8 ± 1.1
and − 1.1 ± 1.2 at
1 year (p = 0.046) and
−0.8 ± 1.4 at 2 years
(p = 0.06)
Mean weight-for-age
SDS at the start of PD
was −1.6 ± 1.5,
0.3 ± 1.5 at 1 year
(p = 0.008) and
0.3 ± 1.8 at 2 years
(p = 0.008)
No significant
difference in height-for-­
age SDS in those who
received supplemental
feeding at the start of
dialysis compared to
those who did not
Change in height-for-­
age SDS was
−0.69 ± 0.68 in those
receiving enteral feeds
versus −0.63 ± 0.66 in
those who did not

30 days,

6 months, and
1 year post
dialysis
initiation

(continued)


B. J. Foster and A. Tsampalieros

494
Table 27.1 (continued)
Study year
published
Parekh
et al. [52]
2001

Population
N = 24
GFR: <65 ml/
min/1.73m2
Age not
reported
Dialysis: N = 7
Transplant:
N = 0
No renal
replacement
therapy: N = 17

Study design
Cohort
Controls from:
1. USRDS
pediatric
growth study
[116] (N = 42)
2. Abitbol
[117] (N = 12)

Intervention
G tube: N = 15
Oral and NG or
G-tube: N = 3
Oral: N = 6
≥100% RDA for
calories
Supplemented
with sodium

Duration
1 and 2 year
follow-up

Waller
et al. [57]
2003

N = 99

Age: 1.6 (0.4 to
6.0)
GFR: <41 mL/
min/1.73m2
(median 22)
All received
conservative
therapy

Cohort study

Tube feeds (NG
and G-tube):
N = 41
The rest of the
participants were
fed orally

3.6 (1.8 to 4.9)
years

Waller
et al. [118]
2005

N = 162
Age: 9.9* (0.3
to 17.1) years
GFR: <60 ml/
min

Conservative:
N = 96
Hemodialysis:
N = 7
Peritoneal
dialysis: N = 19
Transplanted:
N = 40

Cohort study

G-tube: N = 28
The rest of the
participants were
fed normally

1.1* (0.15 to
1.7) years

Outcome
Net increase in
height-for-age SDS of
+0.15 over 2 years in
the treatment group
Treatment group had a
1.37 greater increase in
height-for-age SDS at
1 year compared to
untreated patients in the
USRDS [116] p = 0.017

and a 1.83 greater
increase in height-for-­
age SDS at 2 years
compared to Abitbol
[117] controls p = 0.003
Overall height-for-age
SDS increased by 0.09
per year; however no
significant difference in
change in height among
those receiving tube
feeds versus not
(change in height-for-­
age SDS/year of 0.13
versus 0.05) p = 0.16
Weight- and BMI-for-­
age SDS increased
significantly in those
receiving enteral feeds
vesus not receiving
Change in weight SDS/
year 0.47 versus 0.22
p = 0.005) and change
in BMI-for-age SDS/
year 0.56 versus 0.24
p = 0.002
Overall patients grew
normally (i.e., change
in height-for-age SDS
per year and change in

weight SDS per year
were not different
compared to an
expected mean change
of 0)
There was no
significant difference in
growth in those fed via
G-tube compared to
those fed normally


27  Controlled Enteral and Parenteral Nutrition in Children on Dialysis

495

Table 27.1 (continued)
Study year
published
Cansick
et al. [56]
2007

Population
N = 35
Age: 2.8 (0.25
to 8.90) years
Peritoneal
dialysis: N = 14
Hemodialysis:

N = 4
Both: N = 17

Study design
Case series

Hijazi et al.
[119] 2009

N = 52
Age: 4.4 ± 5.3,
(0.5–18)
months
Peritoneal
dialysis: N = 50
Hemodialysis:
N = 2

Sienna
et al. [61]
2010

N = 20
Age: 1.7* (0.9
to 15.6) years
GFR: 13.8*(3.9
to 61.8) ml/
min/1.73m2
Hemodialysis:
N = 2

Peritoneal
dialysis: N = 6
CKD: N = 11
Unknown:
N = 1
Comparison
group: N = 82
Age:
9.2 ± 3.1 years
GFR: 45.3*(7.4
to 140.1) ml/
min/1.73m2
Hemodialysis:
N = 3
Peritoneal
dialysis: N = 3

Cohort study
comparing
growth in two
different eras
Era 1: Born
1983–1995
N = 23
Era 2: Born
1996–2008
N = 29
Cohort study

Intervention

Tube feeds:
N = 32
By G-tube and/or
NG
≥100% RDA for
calories
Study does not
specify what the
remaining three
received
G-tube: N = 20
NG: N = 32
≥100% RDA for
calories
21 patients were
on growth
hormone

G-tube fed
(N = 20)
≥100% RDA
9/20 were on
growth hormone
Comparison
group included
children with
CKD who did not
have a G-tube
during the study
period (N = 82)

Duration
Until 10 years
of age,
transplanted or
started growth
hormone

Outcome
Children <2 years
showed catch-up
growth in the first year
on dialysis (height-for-­
age SDS 0.31* (−0.78
to 3.13).
No catch-up growth in
older children

25 years of
follow-up

Height-for-age SDS at
most recent encounter
in children from era 2
(−1.4 ± 0.9) was higher
than that in era 1
(−3.0 ± 1.5); p = 0.001

2.9* (0.9 to
11.8) years

Mean height-for-age
Z-score at G-tube
insertion was
−2.35 ± 1.86 and at
removal was
−1.51 ± 0.99 this was a
nonsignificant increase
and was not
significantly different
from comparison
population
Mean BMI-for-age
Z-score increased in
those receiving G-tube
feeds: At G-tube
insertion, it was
−1.22 ± 1.68 and at
removal was
0.43 ± 0.86 p < 0.05
No significant increase
in the comparison group

(continued)