CLINICAL RESEARCH www.jasn.

org

Growth in Very Young Children Undergoing Chronic

Peritoneal Dialysis
Lesley Rees,* Marta Azocar, Dagmara Borzych, Alan R. Watson, Anja Buscher,
Alberto Edefonti,** Ilmay Bilge, David Askenazi, Giovanna Leozappa,
Claudia Gonzales, Koen van Hoeck, Donna Secker,*** Aleksandra Zurowska,
Kai Ronnholm, Antonia H. M. Bouts, Heather Stewart, Gema Ariceta,
Bruno Ranchin, Bradley A. Warady,**** and Franz Schaefer, for the International
Pediatric Peritoneal Dialysis Network (IPPN) registry
*Great Ormond Street Hospital for Children NHS Trust, London, United Kingdom; Hospital Luis Calvo Mackenna,
Santiago, Chile; Center for Pediatrics and Adolescent Medicine, Heidelberg, Germany; Medical University of
Gdansk, Gdansk, Poland; Children & Young Peoples Kidney Unit, Notthingham, United Kingdom; Universitats-
Kinderklinik Essen, Essen, Germany; **Fondazione Ospedale Maggiore Policlinico, Milano, Italy; Istanbul University
Medical Faculty, Istanbul, Turkey; Childrens Hospital of Alabama, Birmingham, Alabama; Diparimento
Nefrologia-Urologia, Unita` di Dialisi, Rome, Italy; Hospital Sotero del Ro, Santiago, Chile; University Hospital
Antwerp, Edegem, Belgium; ***Hospital for Sick Children, Toronto, Canada; HUCH Hospital for Children and
Adolescents, Helsinki, Finland; Academic Medical Center, Amsterdam, Holland; University of North Carolina,
Chapel Hill, North Carolina; Hospital de Cruces, Baracaldo, Spain; Hopital Femme Mere Enfant, Lyon, France;
and ****Childrens Mercy Hospital, Kansas City, Missouri

ABSTRACT
Very young children with chronic kidney disease often have difficulty maintaining adequate nutrition, which
contributes to the high prevalence of short stature in this population. Characteristics of the dialysis prescrip-
tion and supplemental feeding via a nasogastric (NG) tube or gastrostomy may improve growth, but this is
not well understood. Here, we analyzed data from 153 children in 18 countries who commenced chronic
peritoneal dialysis at 24 months of age. From diagnosis to last observation, 57 patients were fed on
demand, 54 by NG tube, and 10 by gastrostomy; 26 switched from NG to gastrostomy; and 6 returned from
NG to demand feeding. North American and European centers accounted for nearly all feeding by gastros-
tomy. Standardized body mass index (BMI) uniformly decreased during periods of demand feeding and
increased during NG and gastrostomy feeding. Changes in BMI demonstrated significant regional variation:
26% of North American children were obese and 50% of Turkish children were malnourished at last

CLINICAL RESEARCH
observation (P 0.005). Body length decreased sharply during the first 6 to 12 months of life and then
tended to stabilize. Time fed by gastrostomy significantly associated with higher lengths over time (P
0.001), but adjustment for baseline length attenuated this effect. In addition, the use of biocompatible
peritoneal dialysate and administration of growth hormone independently associated with improved length,
even after adjusting for regional factors. In summary, growth and nutritional status vary regionally in very
young children treated with chronic peritoneal dialysis. The use of gastrostomy feeding, biocompatible
dialysis fluid, and growth hormone therapy associate with improved linear growth.

J Am Soc Nephrol 22: 23032312, 2011. doi: 10.1681/ASN.2010020192

Received February 17, 2010. Accepted June 28, 2011.
Published online ahead of print. Publication date available at
www.jasn.org.
Correspondence: Dr. Lesley Rees, Renal Office, Great Ormond
Street Hospital for Children NHS Trust, London WC1N 3JH,
United Kingdom. Phone: 0207-762-6725; Fax: 0207-829-8841;
E-mail: Reesl@gosh.nhs.uk
Copyright 2011 by the American Society of Nephrology

J Am Soc Nephrol 22: 23032312, 2011 ISSN : 1046-6673/2212-2303 2303

 CLINICAL RESEARCH www.jasn.org
One-third of total postnatal statural growth occurs during the
first 2 years of life. Hence, early growth is crucial for realization
of the growth potential of children born with chronic kidney
disease (CKD). Difficulties with spontaneous feeding, vomit-
ing, and periods of inadequate intake because of infections and
surgery, along with the very rapid growth at this age and there-
fore high calorie and protein requirements, can rapidly lead to
loss of as much as 2 height SD scores (SDS).1 4 Some centers
report good growth with the use of enteral feeding, but this is
by no means universal.2,3,511
The International Pediatric Peritoneal Dialysis Network
(IPPN) was established in 2007. This prospective registry col-
lects comprehensive patient clinical and laboratory informa-
tion from 69 centers in 25 countries around the world that care
for children on chronic peritoneal dialysis (CPD). All children
starting CPD in each center are registered with the IPPN, and
data reporting continues as long as CPD is performed. Such a
database offers the potential to analyze and correlate clinical
practice and outcomes in many patients.
The objective of this study was to determine associations of
feeding practices and other dialysis-related factors with length
and weight gain in children who commenced CPD within the
first 2 years of life.
RESULTS
Study Population
All children entering the registry at age 2 years between
March 2007 and November 2009 were entered into the study.
This comprised 153 children (61% boys) followed at 49 pedi-
atric nephrology centers in 18 countries. Children were from
Europe (n 67), Latin America (n 33), North America (n
27), Turkey (n 20), and Asian countries (n 6).
Detailed prospective longitudinal information was avail-
able 6, 12, 18, and 24 months after study enrollment in 84, 57,
39, and 23 subjects, respectively. Forty-five (29%) children left
the study early because they died (n 8), were transplanted
(n 19), transferred to hemodialysis (n 12), were lost to
follow-up (n 4), or their native kidney function recovered
(n 2). Additional retrospective information on length
and/or weight was available for the time of birth in 138, at
peritoneal dialysis (PD) initiation in 131, and at the start of
enteral nutrition in all 87 children receiving enteral feeds.
Kidney disease had been diagnosed antenatally or within
the first week of life in 56%, within the first month in 9%,
within the first year in 29%, and within the second year in 6%
of children. CKD was diagnosed later in the six Asian children
(median 5.7 months) than in those from North America and
Europe (median 0 months, P 0.05), but age at PD initiation
did not differ between regions. Diagnoses were renal hypo/
dysplasia with or without obstruction or reflux (n 84), con-
genital and infantile nephrotic syndrome (n 29), polycystic
kidney disease (n 12), renovascular events including hemo-
2304 Journal of the American Society of Nephrology
lytic uremic syndrome (n 16), oxalosis (n 7), and other/
unknown (n 5).
Fifty-five percent had one or more comorbidities, including
defined syndromes (DenysDrash, Potter, SeniorLoken, Caroli,
Goldenhar, Alagille, PierreRobin, and chromosomal abnormal-
ities) (23%); impaired cognitive development (24%); and abnor-
malities of eye (10%), hearing (5%), pulmonary tract (10%), and
gastrointestinal tract (3%).
Further clinical and laboratory information at the time of
study entry is given in Table 1.
Feeding Patterns
The overall time course of feeding regimens from birth to last
observation is shown in Figure 1. Five feeding patterns were
observed: 57 patients were fed on demand or were offered an oral
dietary supplement from the time of diagnosis to the end of the
observation period. Fifty-two patients received continuous na-
sogastric (NG) tube feeding from a median age of 2 months
(interquartile range 0 to 5) to the end of the observation pe-
riod. In six patients, NG tube feeding was performed for a
median of 5.5 months and then discontinued. Another 26 chil-
dren were switched to gastrostomy feeding after a median of
3.8 months of NG tube feeding. Primary gastrostomy feeding
was instituted in ten patients at a median age of 8.2 (3.5 to 10.6)
months, usually at the time of PD initiation.
Body mass index (BMI) SDS and length SDS were similar in
the enterally fed children and those on demand feeds at birth
and at initiation of PD, and they did not differ at initiation of
enteral feeding between patients starting NG tube or gastros-
tomy feeds. A cross-sectional description of patient character-
istics according to nutritional management at the time of study
entry is given in Table 1. The distribution of BMI SDS and
length SDS at each time point in the children with a constant
feeding modality and at least 6 months of follow-up is shown in
Supplemental Figure 1.
BMI SDS uniformly decreased over time during periods
without enteral feeding, whereas NG tube and gastrostomy
feeding reversed the loss of BMI SDS. The median (interquar-
tile range) annualized change in standardized BMI was 0.54
(1.91) SDS/year during periods of demand feeding versus
0.97(3.43) SDS/year during NG tube feeding (P 0.0005)
and 1.24 (3.24) SDS/year during gastrostomy feeding (P
0.05). At last observation the children with exclusive or pre-
dominant demand feeding (Figure 1, upper panels 1 and 2)
were significantly lighter than the children who received en-
teral feeding (Figure 1, upper panels 3 to 5) (P 0.001).
Length SDS was significantly decreased below 0 at birth,
decreased further during the first 6 to 12 months of life, and
then tended to stabilize. Although growth failure was equally
severe in children fed by demand and in those receiving NG
tube feeds (Figure 1, lower panels 1 to 3), growth appeared to
be better preserved in infants started on or switched to gastros-
tomy feeding (Figure 1, lower panels 4 and 5). Considering
feeding periods of at least 6-month duration, the median
change in standardized length was 1.35 (2.63) SDS/year dur-
J Am Soc Nephrol 22: 23032312, 2011
 Table 1. Patient characteristics at study entry for total cohort and according to feeding method at baseline
All Patients Demand Feeding NG Tube Feeding Gastrostomy Feeding
Number of patients 153 66 54 33
Age at diagnosis of renal disease (months) 0.12 (0 to 2.7) 0.93 (0 to 5.2)c 0.0 (0 to 1.6)a 0.1 (0 to 2)a
Age at start of EF (months) 3.1 (0.1 to 5.8) 1.73 (0.1 to 5.4) 2.2 (0.2 to 7.96)
Age at start of PD (months) 5.0 (1.4 to 0.7.3) 7 (3.2 to 14.1)b 3.4 (0.7 to 5.9)a 6.3 (0.9 to 9.7)b
Age at study entry (months) 10.8 (7.2 to 18) 11.8 (7.4 to 18.6) 9.0 (7.2 to 14.4) 10.8 (7 to 15)

J Am Soc Nephrol 22: 23032312, 2011

Length SDS at birth 0.47 (1.79 to 0.46) 0.47 (1.69 to 0.33) 0.47 (2.58 to 0.13) 0.14 (1.74 to 1.06)
Length SDS at start of EF 1.69 (2.96 to 0.28) 1.77 (3.16 to 0.25) 1.43 (2.58 to 0.05)
Length SDS at start of PD 1.69 (3.45 to 0.19) 1.80 (3.14 to 0.47 2.05 (4.50 to 0.08 1.26 (2.76 to 0.57)
Length SDS at study entry 2.44 (3.72 to 1.30) 2.63 (3.91 to 1.54)c 2.72 (4.12 to 1.69)c 2.06 (3.27 to 0.88)b
Length SDS at study entry excluding infants 2.55 (3.77 to 1.26) 2.63 (3.91 to 1.54)c 2.72 (4.12 to 1.61)c 1.91 (2.83 to 0.24)b
on rhGH
BMI SDS at birth 0.58 1.6 0.17 1.48 0.65 1.55 0.68 1.74
BMI SDS at start of EF 1.14 1.56 1.1 1.37
BMI SDS at PD start 0.66 1.8 0.58 1.58 0.84 2.10 0.62 1.9
BMI SDS at study entry 0.40 1.53 0.58 1.69 0.47 1.40 0.11 1.36
n (%) oligoanuric 83 (54) 43 (65)c 30 (55) 10 (30)a
n (%) with comorbidities 84 (55) 34 (52) 31 (57) 19 (57)
n (%) automated PD 112 (76) 49 (74)c 41 (76)c 22 (96)a,b
PD fluid turnover (L/m2 per day) 5.3 (3.5 to 7.9) 4.3 (2.8 to 6.8)c 5.3 (3.6 to 8.3) 6.6 (5.5 to 9.6)a
Dialytic glucose exposure (g/kg per day) 4.2 (2.9 to 7.1) 3.4 (2.3 to 5.3)b,c 4.5 (3.2 to 7.7)a 6.6 (4.0 to 8.1)a
n (%) using biocompatible PD fluid 66 (43) 25 (38) 27 (50) 14 (42)
n (%) using amino acid PD fluid 8 (5.3) 3 (4.6) 5 (9.3) 0 (0)
n (%) phosphate binders 107 (69.9) 54 (83.1) 34 (62.9) 19 (57.6)
n (%) NaCl supplements 56 (36.8) 19 (29.2)c 22 (40.7) 15 (45.5)a
n (%) bicarbonate supplements 58 (38.2) 29 (44.6)c 22 (40.7) 7 (21.2)a
n (%) growth hormone 6 (4.0) 0 (0)c 2 (3.7) 4 (12.1)a
Hemoglobin (g/dl) 10.8 1.8 10.8 1.7 10.8 1.7 10.8 2.0
Bicarbonate (mmol/L) 24.3 4.6 23.2 4.4 24.9 3.8 25.5 5.8
Albumin (g/L) 34.0 7.4 34.0 7.2 34.3 7.5 33.8 7.5
Urea (mg/dl) 83 45 92 37 72 37 83 48
www.jasn.org

Calcium (mmol/L) 2.40 0.23 2.40 0.25 2.40 0.23 2.42 0.22
Inorganic phosphorus (mmol/L) 1.75 0.51 1.82 0.52 1.66 0.46 1.77 0.56
PTH (pg/ml) 222 (85 to 529) 178 (74 to 510) 247 (97 to 575) 243 (110 to 371)
Total Kt/V urea 3.06 (2.32 to 3.81) 3.0 (2.17 to 3.57) 3.22 (2.32 to 3.94) 2.91 (2.3 to 3.6)
Data are given as mean SD, median (interquartile range), or percent of patients. EF, enteral feeding.

Growth of Very Young Children on PD

Superscript letters indicate significant difference between feeding modality groups: adifferent from demand feeding; bdifferent from NG tube feeding; cdifferent from gastrostomy feeding.
CLINICAL RESEARCH

2305
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Figure 1. Whereas both nasogastric tube (NGT) and gastrostomy (GS) feeding improve nutritional status, only GS feeding associates
with stabilized linear growth in young infants undergoing CPD. The data points represent mean estimates at key time points of postnatal
development, (i.e., birth, commencement of CPD, initiation and discontinuation of nasogastric tube or gastrostomy feeding, enrollment
to IPPN [study entry], and last available observation). Two-dimensional error bars denote the 95% confidence intervals to mean age and
SDS at the respective time point.

ing periods of demand feeding, 0.72 (1.59) SDS/year during
NG tube feeding, and 0.50 (2.47) SDS/year during periods of
gastrostomy feeding (P 0.05 for gastrostomy versus demand
feeds). Length SDS at last observation was significantly greater
in the patients with gastrostomy feeding as compared with
those with demand and/or NG tube feeding (P 0.05).
Regional Variation
Treatment practices, growth, and weight gain were also analyzed
with respect to the region of residence (Figure 2, Table 2). At the
time of study entry, North American children were more likely
to be oligoanuric, using ambulatory PD with a higher dialytic
glucose exposure, and receiving growth hormone than chil-
dren in the other regions. Biocompatible PD fluids were applied
more commonly in European children. Turkish children had sig-
nificantly lower serum albumin and higher inorganic phosphorus
levels and more often received amino-acid-containing PD fluid.
Children from Latin America had the largest residual urine out-
put, the highest rate of phosphate binder, and the lowest rate of
oral sodium chloride (NaCl) supplement administration. NG
tube feeding was used for some time in 74% of North American,
60% of European, 50% of Turkish, 45% of Latin American, and in
one of the six Asian children. Gastrostomy tubes were used in 74%
of North American, 21% of European, 6% of Latin American, and
no Turkish and Asian children (P 0.0001).
BMI SDS dropped from birth to PD initiation in Turkish
children (P 0.001), tended to decrease in Latin American
children, and tended to increase in North American children,
resulting in a significant difference among these regions at the
start of PD (P 0.05). Although these trends continued after
PD initiation, European children significantly improved their
BMI SDS. As a result, BMI SDS at last observation was higher
in North American (P 0.0001) and European (P 0.005)
children than in Turkish children, and BMI SDS was higher in
North American than in Latin American children (P 0.01).
BMI at last observation was below the 5th percentile in 50% of
the Turkish children, and above the 95th percentile in 26% of
the North American infants (P 0.005).
Whereas the postnatal loss of length SDS was more marked
and the mean length SDS at PD initiation was lower in North
American than in children from any other region (P 0.05),
length SDS improved significantly while on PD in North Ameri-
can as compared with children from the other regions (P
0.005). It also developed better in European than in Turkish chil-

2306 Journal of the American Society of Nephrology J Am Soc Nephrol 22: 23032312, 2011
 www.jasn.org CLINICAL RESEARCH

(r 0.30, P 0.0003) and inversely corre-

lated with residual urine volume (r 0.29,
P 0.01), whereas length SDS showed no
associations with these variables.

Recombinant Growth Hormone

Treatment
Length SDS was significantly greater at
study entry in the six children who received
recombinant human growth hormone
(rhGH) at study entry. Eight children who
received rhGH for at least 6 months in the
prospective study showed a 1.50 0.81
SDS increase in standardized length as
compared with no net change (0.05
0.93 SDS) in the untreated children (P
0.0001) (Supplemental Figure 3).

Multivariate Analysis of Factors

Associated with Growth and Weight
Gain
Generalized estimating equation modeling
was used to explore the effect size and sig-
nificance of various factors contributing to
the distribution of length SDS and BMI
SDS in the prospective study. When adjust-
ing for age at PD start and age and BMI SDS
at study entry, BMI increased by 0.5 SDS
per year of exposure to enteral feeding.
Apart from the effect of enteral feeding
Figure 2. Minor regional variation in linear growth despite major differences in nutri-
time, BMI SDS showed no significant trend
tional control in infants undergoing CPD. Course of BMI SDS and length SDS by region
in 67 European, 27 North American, 33 Latin American, and 20 Turkish children. Six
over time. Residence in North America was
children from different Asian countries are not represented. Data are mean 95% associated with significantly higher BMI
confidence intervals. aSignificant change from birth to PD start; bSignificant change SDS, and residence in Turkey was associ-
from PD start to last observation. *P 0.05; ***P 0.001. Reference lines indicate the ated with lower BMI SDS, independent of
50th (SDS 0) and 5th (SDS 1.645) percentiles. enteral feeding (Table 3).
The length SDS, adjusted for age and
dren (P 0.05). Consequently, length SDS at IPPN entry and last length at study entry, age at PD start, and region of residence,
observation were lowest in children from Turkey. did not change significantly with time, but it was significantly
higher in patients receiving biocompatible PD fluid and in
PD Prescription those receiving rhGH for at least 6 months (Table 4). The effect
Children treated with biocompatible PD solutions were signifi- of enteral feeding time was dependent on the inclusion of base-
cantly taller at study entry (length SDS 2.09 1.69) than chil- line length SDS in the model. Without adjustment, length SDS
dren using conventional PD fluids (2.88 1.86, P 0.008). increased by 0.59 0.21 per year of gastrostomy feeding (P
Among the children followed prospectively for at least 6 months, 0.0007) whereas time on NG tube feeding had no significant
length SDS did not change in children on conventional solutions effect. The effect of gastrostomy feeding time lost significance
(0.06 1.96 SDS/year, NS), whereas significant catch-up when correcting for length SDS at baseline (Table 4). Daily PD
growth was observed in those dialyzed with biocompatible PD fluid turnover and the use amino-acid fluid showed no inde-
fluid (0.52 1.82 SDS/year) (Supplemental Figure 2). pendent associations with length SDS.
The children receiving amino-acid PD fluids at study entry
were lighter (BMI SDS 1.61 1.91 versus 0.29 1.47, P
0.006) but did not differ in length SDS, and they did not show any DISCUSSION
difference in BMI or length SDS change over time during follow-
up. BMI SDS at study entry was positively correlated with dialytic Although the importance of nutrition in infancy is undisputed,
glucose exposure (r 0.31, P 0.0001) and PD fluid turnover the role of enteral feeding and its modalities in improving

J Am Soc Nephrol 22: 23032312, 2011 Growth of Very Young Children on PD 2307
 CLINICAL RESEARCH www.jasn.org

Table 2. Patient and treatment characteristics according to region

Characteristics Europe North America Latin America Turkey
Number of patients 67 27 33 20
Age (months)
at diagnosis 0 (0 to 0.9) 0 (0 to 0.3)c,d 1.7 (0.2 to 6)b 0.9 (0 to 4.1)b
at start of enteral feeding 0.9 (0 to 4.7) 0.8 (0.2 to 4.9) 5.4 (3.2 to 9.8) 5.4 (0.7 to 11.6)
at start of PD 4.7 (0.7 to 9.7) 5.3 (1.3 to 8.8) 6.9 (2.9 to 12.1) 3.3 (0.8 to 6.4)
Feeding modality, n (%)
demand feeding 22 (33)b 3 (11)a,c,d 17 (52)b 10 (50)b
NGT 3 demand feeding 1 (2)d 1 (4) 0 (0)d 3 (15)a,c
NGT 30 (45)b 3 (11)a,c,d 14 (42)b 7 (35)b
gastrostomy 5 (8) 4 (15) 1 (3) 0 (0)
NGT 3 gastrostomy 9 (13)b 16 (59)a,c,d 1 (3)b 0 (0)b
n (%) with comorbidities 27 (40.3)b 19 (70.4)a 17 (51.5) 9 (45)
n (%) oligoanuric 25 (43.1)b,c 12 (75)a,c,d 3 (9.4)a,b 6 (30)b
n (%) automated PD 52 (80)b 27 (100)a,c,d 29 (88)b,d 13 (65)b,c
PD fluid turnover 5.3 (3.5 to 9.1)d 6.9 (5.9 to 8.4)d 5.0 (3.5 to 6.5) 3.8 (2.4 to 5.0)a,b
(L/m2 per day)
Dialytic glucose exposure 4.7 (2.8 to 7.1)b,d 7.2 (4.1 to 9.9)a,c,d 3.8 (2.9 to 5.1)b 6.6 (4.0 to 8.1)a,b
(g/kg per day)
n (%) using biocompatible PD fluids 54 (80.6)b,c,d 3 (11.1)a 4 (12.1)a 3 (15)a
n (%) using amino-acid PD fluid 3 (4.5)d 0 (0)d 0 (0)d 5 (25)a,b,c
n (%) phosphate binders 45 (67.2)b,c 11 (40.7)a,c,d 31 (93.4)a,b 15 (75)b
n (%) NaCl supplements 37 (55.2)c,d 10 (37)c 3 (9.1)a,b 5 (25)a
n (%) bicarbonate supplements 17 (25.3)c 5 (18.5)c 25 (75.8)a,b,d 8 (40)c
n (%) growth hormone 2 (3)b 4 (14.9)a,c 0 (0)b 0 (0)
Hemoglobin (g/dl) 11.1 1.7 10.6 2.5 10.7 1.7 10.1 2.2
Bicarbonate (mmol/L) 25.3 4.1d 24.9 6.6d 23.3 3.2 21.7 4.1a,b
Albumin (g/L) 33.7 6.7d 35.4 6.8d 37.1 6.9d 27.9 7.4a,b,c
Urea (mg/dl) 80 44 100 49 84 41 71.2 49
Calcium (mmol/L) 2.42 0.23 2.44 0.28 2.41 0.19 2.30 0.23
Inorganic phosphorus (mmol/L) 1.70 0.36d 1.68 0.62d 1.76 0.41d 2.05 0.75a,b,c
PTH (pg/ml) 140 (49 to 351) 224 (110 to 477) 317 (200 to 523) 509 (97 to 1003)
Total Kt/V urea 3.05 (2.62 to 3.66) 2.36 (1.79 to 3.12) 3.75 (2.89 to 4.14) 3.76 (2.37 to 5.0)
PD medication and biochemical data are given at time of entry to the IPPN study. The six infants from Asian countries are not represented. Data are given as
mean SD, median (interquartile range), or percent of patients. NGT, nasogastric tube.
Superscript letters indicate significant difference between regions: adifferent from Europe; bdifferent from North America; cdifferent from Latin America;
d
different from Turkey.

Table 3. Generalized estimating equation modeling of factors predicting BMI growth has been a controversial topic for
SDS during the observation period many years.511 Analysis of the worldwide
IPPN database adds a novel perspective on
Standardized
Outcome Variable Parameter
95% Confidence
P
the efficacy and global variation of current
Interval growth-promoting strategies in young in-
Estimate SEM
fants and the relative roles of nutritional
BMI SDS
intercept 0.07 0.19 0.45 to 0.31 0.721
measures, dialysis prescription, and other
observation time (years) 0.06 0.18 0.41 to 0.30 0.75 factors. The combination of comprehen-
age at PD start (years) 0.23 0.13 0.01 to 0.47 0.058 sive prospective data collection with retro-
age at study entry (years) 0.05 0.13 0.20 to 0.30 0.71 spective milestone analysis of length and
BMI SDS at study entry 0.70 0.05 0.61 to 0.80 0.0001 weight at birth, PD initiation, and start and
Region of residence (reference: Europe) change of enteral feeding provided a com-
North America 0.39 0.18 0.05 to 0.74 0.026 plete picture of early infantile growth pat-
Latin America 0.19 0.13 0.44 to 0.07 0.153 terns.
Turkey 0.55 0.20 0.95 to 0.16 0.006 We observed a high prevalence of early
Asia 0.21 0.33 0.43 to 0.85 0.516
growth failure across different regions of
Time on enteral feeding (years) 0.50 0.23 0.04 to 0.96 0.032
Dialytic glucose exposure (g/kg per day) 0.03 0.02 0.08 to 0.02 0.182
the world. Notably, length was already
Standardized parameter estimate indicates a unit greater BMI SDS at follow-up per unit of
slightly reduced at birth, compatible with
independent variable. a link between intrauterine growth con-

2308 Journal of the American Society of Nephrology J Am Soc Nephrol 22: 23032312, 2011
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Table 4. Generalized estimating equation modeling of factors predicting institution of enteral feeding.12 However,
length SDS during the observation period only 41% of the infants in this study were
Standardized enterally fed even after the start of dialysis,
95% Confidence
Outcome Variable Parameter P reflecting marked global variation in feed-
Interval
Estimate SEM ing strategies and, possibly, a perceived
Length SDS lower need for intensified nutritional man-
intercept 0.76 0.23 1.98 to 0.31 0.0008 agement in infants less affected by feeding
age at PD start (years) 0.16 0.13 0.10 to 0.42 0.226 problems.
age at study entry (years) 0.05 0.12 0.19 to 0.29 0.672 Our analysis clearly demonstrates that
length SDS at study entry 0.88 0.03 0.83 to 0.94 0.0001 NG tube and gastrostomy feeding are effec-
Region of residence (reference: Europe)
tive in improving the nutritional status, as
North America 0.14 0.20 0.25 to 0.54 0.477
indicated by BMI SDS, in young infants
Latin America 0.13 0.16 0.17 to 0.44 0.393
Turkey 0.02 0.17 0.34 to 0.31 0.928
with advanced and end-stage CKD. How-
Asia 0.22 0.21 0.63 to 0.18 0.282 ever, the relationship between enteral feed-
Observation time (years) 0.09 0.12 0.33 to 0.15 0.463 ing and growth seems to be more complex.
Time with NG tube (years) 0.03 0.18 0.32 to 0.38 0.862 The restitution of a normal BMI distribu-
Time with gastrostomy (years) 0.25 0.22 0.21 to 0.73 0.211 tion by NG tube feeding did not prevent
Growth hormone treatment 0.57 0.24 0.10 to 1.04 0.017 further growth failure, at least within the
Use of biocompatible PD fluid 0.42 0.12 0.19 to 0.65 0.0004 given time window of observation. Infants
Use of amino-acid PD fluid 0.13 0.17 0.36 to 0.11 0.296 initiated on or switched to gastrostomy
PD fluid turnover (L/m2 per day) 0.01 0.02 0.03 to 0.05 0.708 feeding showed somewhat better preserva-
Standardized parameter estimate indicates a unit greater length SDS at follow-up per unit of
independent variable (constant factors: presence 1).
tion of growth as compared with demand-
fed children. The beneficial effect of gastros-
tomy feeding prevailed when correcting for
ditions and renal development. Severe growth failure oc- confounding factors such as region of residence of the prospec-
curred before and early after initiation of dialysis, followed by tive study, but it lost significance when correcting for length
stabilization of growth rates in the second year of life. In view of SDS at first observation, probably because length had already
the excellent growth reported for this age group in single-cen- normalized in some children who had started gastrostomy
ter studies, the observed outcomes show a large potential for feeding before entering the IPPN registry. We can only specu-
improvement at the global population level. late why gastrostomy use was associated with superior growth.
Although this observational study cannot prove causalities, The most likely explanation for the difference between NG and
it identified several factors and conditions consistently associ- gastrostomy feeding is a reduction in vomiting: the presence of
ated with early infantile growth patterns that deserve attention. a NG tube may act as a stent passing through the gastroesoph-
Nutrition is generally considered to be the most important ageal junction. This will usually improve with a gastrostomy.14
determinant of body growth in infancy. Calorie and protein Also, a slightly higher fraction of gastrostomy patients received
requirements are proportionately greater at this age than at any oral sodium supplements, although the difference was signifi-
other time of life. Significant protein losses occur in the peri- cant only when compared with children fed by demand.
toneal dialysate.4,12 Infants on CPD are often difficult to feed The marked regional variation and overall low rate of gas-
and are prone to gastroesophageal reflux and vomiting. This is trostomy use would suggest that the findings in this paper
attributed to uremic anorexia, raised intra-abdominal pressure should prompt a reconsideration of enteral feeding policies for
due to PD,13 and the need to concentrate the feed in oliguric young children on CPD. We do not know why so few children
infants. Severe vomiting may in itself compromise growth be- had a gastrostomy; one reason may be a relative reluctance to
cause of the ensuing fluid and electrolyte imbalances. perform an open gastrostomy procedure, which is recom-
Enteral feeding by NG or gastrostomy tube is regarded as a mended instead of percutaneous placement when patients are
key measure to optimize nutrition and growth in young in- already established on PD.14,15
fants.14 An additional benefit of tube feeding beyond the pro- The lack of detailed data on the prescription and actual
vision of energy, protein, and fluid is the ability to use it to intake of nutrients is a limitation of our study. These types of
administer medications such as NaCl supplements, which are data are difficult to collect and assess accurately. Reassuringly,
commonly required both in polyuric infants with structural a designated renal dietician was available in all but 2 of the 49
renal abnormalities and in anuric infants with high ultrafiltra- contributing centers. Also, the KDOQI pediatric nutrition
tion-related losses4,12; salt depletion is known to limit guidelines12 were made available through the IPPN website
growth.10 Provision of NaCl by tube is much easier and causes and were consulted regularly by the centers. Nevertheless, we
less vomiting than administration by mouth. observed marked regional variation in nutritional outcomes,
The recent Kidney Disease Outcomes Quality Initiative with a 0.6 SD negative and 0.4 SD positive mean BMI differ-
(KDOQI) pediatric nutritional guidelines recommend early ence attributable to children living in Turkey and the United

J Am Soc Nephrol 22: 23032312, 2011 Growth of Very Young Children on PD 2309
 CLINICAL RESEARCH www.jasn.org
States as compared with Europe, respectively, independent of
feeding modalities. These differences may be explained by sub-
stantial global variation regarding the contents and/or effectu-
ation of dietary prescriptions. Of course, we cannot rule out
other unidentified confounding factors contributing to the re-
gional differences in BMI SDS.
It is remarkable that the regional differences in nutritional
status appeared to align with linear growth patterns only in the
milestone analysis from birth to study entry, but not in the
multivariate analysis of the prospective study. Although wors-
ening malnutrition coincided with growth failure in the Turk-
ish children, infants in North America, while continuously
gaining BMI SDS also grew significantly less well than Euro-
pean children while followed longitudinally. In Europe major
malnutrition was prevented throughout the disease process,
but growth retardation still developed, albeit at a milder degree
than in the other regions. These findings are compatible with
the view that growth in infancy is a multifactorial process, with
adequate nutrition being just one of several prerequisites.
Unexpectedly, the use of biocompatible PD fluids low in
toxic glucose degradation products was consistently associated
with better body growth. The association prevailed even after
correction for nutritional status and region and was quantita-
tively stronger than the effect of gastrostomy feeding. Although
the causality postulate would require testing by controlled
studies, one might speculate about a growth-preserving effect
of attenuated local and systemic inflammatory processes and
carbonyl stress accomplished with reduced GDP exposure.
In contrast, the use of amino-acid PD solutions was not
associated with improved growth and was actually a negative
predictor of BMI SDS by univariate analysis, most likely be-
cause of bias by indication related to the selective use of amino
acid solutions in the most malnourished children.
Increasing evidence from uncontrolled and controlled trials
supports the efficacy of rhGH in very young children with
CKD.16 18 Although provided to only eight children for at least
6 months, rhGH therapy was independently associated with
improved growth in this study. The severe overall growth re-
tardation observed even in the European and North American
centers and the fact that even gastrostomy feeding only miti-
gated but did not readily reverse growth failure should be rea-
son to consider early institution of rhGH in young infants who
are failing to grow adequately despite provision of an adequate
dietary intake.
In conclusion, the IPPN database is unique in its ability to
study and compare protocols throughout the world and, by
virtue of the numbers of patients for study, to be able to ascer-
tain the best practice. Because complete case reporting is
achieved, information bias is kept to a minimum. Interroga-
tion of the database has shown severe early growth failure in
infants on CPD and an important association between early
gastrostomy feeding and better preservation of growth rates at
this crucial time. It has also generated interesting hypotheses
regarding additional dialysis-related factors of influence to be
tested in future clinical trials.
2310 Journal of the American Society of Nephrology
CONCISE METHODS
Data Collection
The following data were collected at entry to the registry: patient char-
acteristics (age, sex, diagnosis and comorbidity, age at diagnosis of
CKD, age at start of enteral feeding and CPD, and the presence of
residual urine), feeding method (demand feeding, NG tube or gas-
trostomy), medications (use of erythropoietin, iron, sodium or bicar-
bonate supplements, vitamin D, phosphate binders, and/or rhGH),
blood levels (hemoglobin, bicarbonate, calcium, phosphate, parathy-
roid hormone, and albumin), dialysis program (PD modality, dialy-
sate turnover, average dialysate glucose concentration, type of fluid
used, Kt/V urea, and creatinine clearance), and supine length weight
and BMI (length was measured to the nearest 5 mm by infantometers
in 12 centers and by tape in 28 centers). The above observations were
collected prospectively at 6-month intervals. In addition, anthropo-
metric data at birth, at the start of PD, and at the start and at any
change of enteral feeding modalities were collected retrospectively.
The prospective analysis was terminated on November 30, 2009 or
alternatively if the patient died, was transplanted, or transferred to
chronic hemodialysis.
Statistics
Length and BMI were normalized to SDS using the World Health
Organization 2006 normative values for children up to age 5 years.19
Data were checked for normal distribution by the KolmogorovSmir-
noff test. Data are expressed by mean SD for normally distributed
and by median and interquartile range for non-normally distributed
variables. Between-group differences in group means (log-trans-
formed in case of non-Gaussian distribution) were assessed by t test
for two-group comparisons and by ANOVA followed by Newman
Keuls testing for multiple comparisons. Differences in proportions
were assessed using 2 tests.
Generalized estimating equation analysis was performed on the
prospective part of the study, which started with entry to the IPPN
registry. Associations of time-invariant factors (region of residence,
6 months of growth hormone treatment, and use of biocompatible
or amino-acid PD fluid) and time-variant covariates (cumulative ob-
servation time with NG tube or gastrostomy, PD fluid turnover, and
dialytic glucose exposure) related to nutritional and dialytic manage-
ment with the evolution of length and BMI SDS were explored using
the Repeated statement of the SAS GENMOD procedure (time vari-
able: observation time in prospective study). An autoregressive cor-
relation matrix structure was assumed. Data were analyzed using SAS
version 9.2 (SAS Institute, Cary, NC).
ACKNOWLEDGMENTS
The authors gratefully acknowledge the support of the International
Society for Peritoneal Dialysis, Baxter Health Care, Fresenius Medical
Care, Ipsen, Pfizer, IBM, and Sandoz. We also appreciate the contin-
ued dedicated support of IPPN by the medical and nursing staff in all
collaborating centers.
J Am Soc Nephrol 22: 23032312, 2011

The following principal investigators are contributing to the IPPN
registry:
Argentina: E. Sojo, Hospital de Pediatria Garrahan, Buenos Aires;
P.A Coccia, Hospital Italiano de Buenos Aires; A. Suarez, Hospital de
Ninos Sor. Maria Ludovica La Plata; P.G. Valles, Hospital Pediatrico
Humberto Notti, Mendoza; R. Salim, Rennius S.A. Salta. Belgium: K.
van Hoeck, University Hospital Antwerp, Edegem. Brazil: V. Koch,
Instituto da Crianca Hospital das Clinicas FMUSP, Sao Paulo. Can-
ada: J. Feber, Childrens Hospital of Eastern Ontario, Ottawa; D.A.
Geary, Hospital for Sick Children, Toronto; C. White, BC Childrens
Hospital, Vancouver. Chile: M. Valenzuela, Hospital Guillermo Grant
Benavente, Concepcion; J. Villagra, Hospital Base, Osorno; F. Cano,
Hospital Luis Calvo Mackenna, Santiago, M.A. Contreras, Roberto
del Rio Hospital, Santiago; A. Vogel, Pontivicia Universidad Catolica
de Chile, Santiago; P. Zambrano, Hospital Dr. Gonzales Cortes, San-
tiago, P. Berrocal Hospital Sotero del Rio, Santiago. China: M.C.
Chiu, Department of Pediatric & Adolescent Medicine, Hong Kong,
H. Xu, Childrens Hospital of Fudan University, Shanghai. Czech Re-
public: K. Vondrak, University Hospital Motol, Prague. Finland: K.
Ronnholm, Hospital for Children and Adolescents, Helsinki; France:
B. Ranchin, Hopital Femme Me`re Enfant, Lyon; T. Ulinski, Armand
Trousseau Hospital, Paris; M. Fischbach, Childrens Dialysis Center,
Strasbourg. Germany: R. Buscher, Childrens Hospital Essen; M.
Kemper, University Medical Center, Hamburg; L. Pape, Medical
School, Hannover; F. Schaefer, D. Borzych, Center for Pediatrics and
Adolescent Medicine, Heidelberg; J. Misselwitz, Kidney Center for
Children and Adolescent; G. Klaus, University Hospital, Marburg; D.
Haffner, University Childrens Hospital, Rostock. Greece: F. Papach-
ristou, Aristoteles University, Thessaloniki. India: A. Bagga, All India
Institute of Medical Sciences, New Delhi; M. Kanitkar, Armed Forces
Medical College, Pune. Italy: E. Verrina, G. Gasini Institute, Genova;
A. Edefonti, Fondazione Ospedale Maggiore Policlinico, Milano; G.
Leozappa, Dipartimento Nefrologia-Urologia, Rome. Israel: D. Lan-
dau, Soroka Medical Center, Beer-Sheva. Korea: I. S. Ha, Dialysis
Center for Children and Adolescents, Seoul; K. H. Paik, Samsung
Medical Center, Seoul. Macedonia: E. Sahpazova Pediatric Clinic,
Skopje. The Netherlands: J.W. Groothoff, Academic Medical Center,
Amsterdam. Nicaragua: Y. Silva, Hospital Infantil de Nicaragua, Ma-
nagua. Poland: A.M. Zurowska, D. Borzych, Medical University,
Gdansk; D. Drozdz, University Childrens Hospital, Krakow; M.
Lipka, Childrens Memorial Health Institute, Warsaw, M. Sczepan-
ska, Dialysis Division for Children, Zabrze. Romania: O. Brumariu,
St. Maria Childrens Hospital, Iasi. Singapore: H.K. Yap, Shaw-NKF-
NUH Childrens Kidney Center. Spain: G. Ariceta, Hospital de Cru-
ces, Baracaldo. Turkey: A.S. Bakkaloglu, Hacettepe University, An-
kara; S. Bakkaloglu, Gazi University, Ankara; I. Bilge, Department of
Pediatric Nephrology, Capa-Istanbul; E. Serdaroglu, Dr. Behcet Chil-
dren Research and Educational Hospital, Izmir; A. Bal, Tepecik Chil-
dren and Research Hospital, Izmir; S. Mir, Ege University Faculty of
Medicine, Izmir-Bornova. United Kingdom: L. Rees, Great Ormond
Street Hospital, London. A.R. Watson, Children & Young Peoples
Kidney Unit, Notthingham. Uruguay: J. Grunberg, SE.N.NI.AD,
Montevideo. United States: L. Greenbaum, Childrens Healthcare
Pediatric Dialysis Unit, Atlanta; A. Neu, Johns Hopkins Hospital,
Baltimore; D. Askenazi, Childrens Hospital of Alabama, Birming-
J Am Soc Nephrol 22: 23032312, 2011
www.jasn.org CLINICAL RESEARCH
ham; D. Gipson, University of North Carolina, Chapel Hill; H.
Patel, Childrens Hospital, Columbus; S. Pottoore, Childrens
Medical Center, Dallas; V. Dharnidharka, Division of Pediatric
Nephrology, Gainesville; T. Bunchman, Helen DeVos Childrens
Hospital; A. Chua, Texas Childrens Hospital, Houston; B.A.
Warady, Childrens Mercy Hospital, Kansas City; J. Zaritsky,
UCLA Medical Center, Los Angeles.
DISCLOSURES
None.
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J Am Soc Nephrol 22: 23032312, 2011