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Biomedical Journal of Indonesia Vol 7 Issue 3 2021
The Effectiveness of Giving Growth Hormone to Children with Chronic Kidney
Disease: Systematic Literature Review
Irhamni Nur Afdhila1, Fitrisia Amelin2*, Gardenia Akhyar3
1Medical Education Program, Faculty of Medicine, Universitas Andalas, Padang 2Department of Pediatricts, Faculty of Medicine, Universitas Andalas, Padang/RSUP Dr M Djamil 3Department of Dermatovenerology, Faculty of Medicine, Universitas Andalas, Padang/RSUP Dr M Djamil
A R T I C L E I N F O
Keywords:
Growth Hormone Children
Chronic Kidney Disease Effectiveness
Corresponding author: Fitrisia Amelin
E-mail address:
[email protected]
All authors have reviewed and
approved the final version of the
manuscript.
https://doi.org/10.32539/BJI.v7i3.537
A B S T R A C T
Chronic Kidney Disease (CKD) can cause growth problems in children. This condition
will affect children’s social life and increase morbidity and morta lity. Growth
hormone (GH) is one of medication that has been used for treatment of impaired
growth in children with chronic kidney disease. In Indonesia, this management has
not been provided, because it is expensive and its effectiveness is uncertain. This
research was conducted to determine the effectiveness of growth hormone in
increasing linear growth in children with CKD. This study is a systematic review of
the Randomized Controlled Trial (RCT) study to determine the effectiveness of growth
hormone as a treatment for children with CKD. Literature search was conducted
using five databases, namely Pubmed, Google Scholar, DOAJ, BMC and CENTRAL
that matched the inclusion and exclusion criteria. The guide used in the literature
selection was the PRISMA flow chart. A Total of 10 studies were included in the
systematic review. Growth hormone is effective in increasing linear growth in
children with CKD. Generally there was a significant increase in height (standard
deviation (SD)), high velocity (SD or cm) in the therapy group compared to the control
group. The dose of growth hormone that is given varies, but the most is 4 IU / m2 /
day, once a day, by subcutaneous injection. The duration of growth hormone
administration varied from 6 months to 5 years with an average of 1.7 years. Growth
hormone did not aggravate kidney problems in children with CKD and can increase
important factors in bone formation, namely alkaline phosphatase and osteocalcin.
1. Introduction
According to Kidney Disease Improving Global
Outcome (KDIGO), chronic kidney disease (CKD) is a
kidney disorder in the form of structural and kidney
function abnormalities that occur for more than 3
months and affect health, with or without a decrease
in the glomerular filtration rate (GFR). 1
CKD is a serious health problem in children, with
increasing morbidity and mortality, as well as
causing significant economic and social problems.2
The results of the Global Burden of Disease (GBD)
study , in general, the incidence of CKD has increased
significantly in the last 27 years. CKD became the
18th leading cause of death in the world in 2016,
where previously it was ranked 27th in 1990.3 The
exact incidence rate in children is very limited, it is
estimated that the incidence of CKD in children is
higher than the existing data, because there are
many cases that do not occur. not detected.2
In Europe, the incidence of CKD in children was
about 12 out of a million population in 2008. This
number is comparable to the population in other
western countries.5 Research in Iran in 2011, there
were 16.8 out of one million children with chronic
kidney disease with a mortality rate of 18.4%.
Younger age is a predictor of death.6 In 2008,
approximately 9 out of a million children underwent
renal replacement therapy worldwide.4 In Indonesia,
there is no national data on the incidence of CKD in
children. According to data from RSCM Jakarta,
Biomedical Journal of Indonesia Journal Homepage: https://www.jurnalkedokteranunsri.id/index.php/BJI/index
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found 382 CKD patients who seek treatment at the
Department of Pediatrics in 2006 and 2007. At RSUP
dr. Kariadi during the 2015-2017 period, there were
566 pediatric patients with kidney disorders who
came for treatment, 37.6% of them were children
aged 5-12 years, 29.4% were children under five, and
29% were teenagers. 7
CKD in children is one of the diseases associated
with growth disorders in children.8 The cause of this
growth multifactorial disorder, ga ngguan nutritional
intake, metabolic acidosis which would induce the
degradation of proteins, causing muscle wasting,
production of endogenous corticosteroids and organ
resistance to growth hormone. In addition, decreased
kidney function in CKD children results in decreased
renal phosphate excretion and impaired
gastrointestinal calcium reabsorption , resulting in
hyperphosphatemia and hypocalcemia. Low calcium
in the blood stimulates parathyroid hormone to take
calcium from the bones into the blood. This is very
dangerous for the integrity and growth of the child's
bones.9 Growth problems in CKD children last for a
long time, so it can affect linear growth which is a
manifestation of long-term growth disorders. 10
Linear growth disorders in CKD children must be
intervened immediately so that there is no severe loss
of height in adulthood.9 Various approaches are
needed in the management of linear growth disorders
in children with CKD.11 Supplementation of protein
and calories alone is not enough to control
malnutrition and growth disorders in CKD children,
special therapeutic interventions also need to be
given.12 One of the special interventions that has
been studied is the administration of growth hormone
in CKD children. 8 The administration of
growth hormone in CKD children has been
recommended in several countries, and has been
approved for use by the Food and Drug
Administration (FDA).8.13 However, in Indonesia, the
administration of growth hormone has not been used
as the main therapy to improve height and weight in
children with CKD, because the price of growth
hormone is expensive and its effectiveness in treating
linear growth disorders in children with CKD is still
uncertain. Growth disorders in CKD children in
Indonesia are only given general management, such
as improving nutrition, giving vitamin D, low-
phosphate nutrition and phosp
hate binders, and preventing anemia
progression.13Assessment of the effectiveness of
growth hormone as therapy in children with CKD
needs to be done, through direct research by giving
growth hormone to children with CKD. This research
has been carried out and is still being carried out
today. However, each study was conducted with
different methods and obtained different research
results, which raises doubts.
A further literature concerning the role of growth
hormone in children with CKD are needed to compare
the differences in each study. Primary literature with
RCT studies is one of the best sources for conducting
such literature reviews. O leh therefore, researchers
are interested in creating a literature review entitled
" Effective Provision of Growth Hormone in Children
with Chronic Kidney Disease Study Randomized
Controlled Trial (RCT): a Systematic Literature
Review.
2. Research Methods
This research is a literature review with a
systematic literature review on the effectiveness of
growth hormone in children with chronic kidney
disease (CKD). The sources taken are primary
literature found in pubmed, google scholar, DOAJ,
BMC, CENTRAL, with the keywords "chronic kidney
disease or renal insufficiency chronic and child or
child health and growth hormone or human growth
hormone and stunting or growth disorder".
The research taken is research that meets the
inclusion and exclusion criteria based on the PICOS
framework. Inclusion criteria: RCT study in English,
focusing on CKD children receiving growth hormone,
there is a comparison/control group and the results
are the effect of hormone administration on CKD
children's height and the full text can be downloaded.
Exclusion criteria: studies that focus on other
diseases and studies where other interventions are
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more dominant.
The literature selection process uses a flow chart
of preferred reporting items for systematic reviews
and meta-analyses (P RISMA), and the quality of the
selected studies is assessed using The Joanna Briggs
Institute (JBI) critical appraisal for randomized
controlled trial, which consists of 13 questions. Each
question is given a score of “1” for a yes answer, and
a score of “0” for a no or unknown answer. The
literature to be extracted and analyzed is literature
with a total score of 7 (percentage >50%).
3. Results
Literature Selection Results
Figure 1. Literature Selection Results
A total of 11 primary articles were obtained after
selecting the PRISMA flow chart. The article is first
assessed for quality using JBI critical appraisal. The
results of the study quality assessment are two
studies with a score of 11, one study with a score of
10, one study with a score of 9, two studies with a
score of 8, four studies with a score of 7, and one
study with a score of 4. were included because the
percentage did not exceed 50%, so the total studies
to be extracted and analyzed were 10 studies.
14,15,16,17,18,18,20,21,22,23,24
Iden
tifi
cati
on
Sc
ree
nin
g Fe
asi
bili
ty
Incl
usio
n
Study results identified
through database search (total=39)
DOAJ (n=6), BMC (n=4)
Pubmed (n-16) Google Schoolar (n=11)
CENTRAL, (n=2) DATABASE SEARCH
(Total=39)
Identified from
preliminary studies (n=2)
selection result after duplicate article is deleted (n=36)
Study (full text) assessed
feasibility (n=21)
Study executed because:
title and abstract do not
match (n=9)
no full text (n=5)
not in English (n=1)
DATABASE SEARCH (Total=39)C
Studies included in
systematic review
(n=11)
Study executed because: Thesis (n=1)
Case report (n=3) irrelevant study (n=6)
DATABASE SEARCH (Total=39)C
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Data Extraction Results
Table 1. The Effect of Growth Hormone on Height in CKD Children
No. Researcher Name Year Result (Height)
1. Guest G. et al; Prancis30 1998 Height (SD) increased statistically significantly in the therapy group compared to the control
group
High speed (cm/year) increased statistically
significantly in the therapy group compared to
the control group
2. Fine RN, et al; Amerika34 2002 Height (SD) increased statistically significantly
in the therapy group compared to the control group
3. Koelega ACS, et al; Belanda35 1991 High speed (cm/6 months) increased statistically significantly in the therapy group
compared to the control group
4. Darabi A, et al; Iran27 2019 Height (SD) increased statistically significantly
in the therapy group compared to the control group.
5. Dyck MV, et al; Belgia29 2001 Height (SD) increased significantly in the
therapy group compared to the control group.
6. Koelega ACS, et al; Belanda37 1994 High speed (SD) increased clinically
significantly in the therapy group compared to the therapy and control group
7. Sluis IM, et al; Belanda32 2000 Height (SD) increased statistically significantly in the therapy group compared to the control
group
8. Hertel NT, et al; Denmark36 2002 Height (sd) increased in both groups, there was
no clinically significant difference between both of them.
High speed (sd) increased in both groups, there
was no clinically significant difference between boh of them
9. Mencarrelli F, et al Italia28 2009 Height (sd) increased statistically significantly in the therapy group, there was no difference
between the therapy and control groups
10. Haffiner D, et al; Jerman 31 2000 Height (SD) increased statistically significantly
in the therapy group compared to the control group
Table 2. Dosage, frequency, method of administration, and duration of administration of growth hormone in
children with CKD
No. Researcher
Name
Year Dosage Frequency Method of
Administration
Duration
1. Guest G. et al; Prancis30
1998 30 IU/m2/week equal to 4.2 IU/m2/day
Once a day Subcutaneous injection
1 years
2. Fine RN, et al;
Amerika34
2002 0.05 mg/kg/day equal
to 4 IU/m2/day
Once a day Subcutaneous
injection
1 years
3. Koelega ACS, et al; Belanda35
1991 4 IU/m2/day Once a day Subcutaneous injection
6 months
4. Darabi A, et al; Iran27
2019 4 IU/m2/day Once a day Subcutaneous injection
2 years
5. Dyck MV, et al; Belgia29
2001 1 IU/kg/week equal to 0.14 IU/kg/week
Once a day Subcutaneous injection
1 years
6. Koelega ACS, et al; Belanda37
1994 4 IU/m2/day and 2 IU/m2/day
Once a day Subcutaneous injection
2 years
7. Sluis IM, et al; Belanda32
2000 4 IU/m2/day Once a day Subcutaneous injection
2 years
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No. Researcher
Name
Year Dosage Frequency Method of
Administration
Duration
8. Hertel NT, et al;
Denmark36
2002 4 IU/m2/day and 2
IU/m2/day
Once a day Subcutaneous
injection
1 years
9. Mencarrelli F,
et al Italia28
2009 0.05 mg/kg/day equal
to 4 IU/m2/day
Once a day Subcutaneous
injection
2 years
10. Haffiner D, et
al; Jerman 31
2000 1 IU/kg/week equal to
0.14 IU/kg/week
Once a day Subcutaneous
injection
5 years
Table 3. Safety of Giving Growth Hormone to CKD Children
No. Researcher Name Year Result
(Height)
1. Guest G. et al; Prancis30 1998 Serum creatin increased slightly, but there
were no significant differences between the therapy and control groups
Inulin clearance decreased slightly, but there was no significant difference between the
therapy and control groups
1 patient in the therapy group with side effects
of papilledema
2. Fine RN, et al; Amerika34 2002 There was no significant difference in serum
creatinine between the two groups
3. Koelega ACS, et al; Belanda35 1991 No explanation
4. Darabi A, et al; Iran27 2019 GFR was slightly improved in the therapy group but was not significant
5. Dyck MV, et al; Belgia29 2001 Creatinum clearance was no significant difference between the two groups
6. Koelega ACS, et al; Belanda37 1994 No explanation
7. Sluis IM, et al; Belanda32 2000 GFR there was no significant difference
between the two groups
8. Hertel NT, et al; Denmark36 2002 GFR there was no significant difference
between the two groups
9. Mencarrelli F, et al Italia28 2009 No explanation
10. Haffiner D, et al; Jerman 31 2000 No explanation
4. Discussion
Growth Hormone Disorders in Children with
CKD
Growth hormone is secreted by the anterior
pituitary gland under stimulation by growth hormone
releasing hormone (GHRH) from the hypothalamus.
This growth hormone will bind to its receptors and
activate insulin growth factor-1 (IGF-1) in tissues,
which is a precursor for cartilage growth, cell
replication, protein synthesis, and carbohydrate
balance. IGF-1 produced in some tissues will be
released in the blood. Generally, this IGF-1 binds to
insulin growth factor binding protein (IGFBP).25
However, IGF-1 which is not bound to IGFBP (free
IGF-1), is more effective than bound IGF-1. In
children with chronic kidney disease (CKD), IGF-1
does not work optimally, because the kidney's ability
to excrete IGFBP is reduced, so circulating IGFBP
increases which causes bound IGF-1 to increase and
free IGF-1 to decrease. 25,26 In addition, another cause
of IGF-1 function is not optimal in CKD children due
to impaired signal transduction through janus kinase
2/signal transducer and activator transcription5
(JAK2/STAT5), which is a growth hormone
intermediary to activate IGF-1. which can be seen in
Figure 2 27
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Figure 2 . 27 . Transduction Disturbance Mechanism
The Effect of Growth Hormone on Children with
CKD . Height
Giving growth hormone is part of the management
of growth disorders in CKD children. Growth
hormone affects the balance between IGF-1 which
stimulates growth and inhibits IGFBP, so that the
ratio of IGF-1/IGFBP increases. 28 In a review that
has been conducted, several studies have shown a
significant increase in IGF-1 in the treatment group
compared to the control group. 16,17,18,19,22,23
Growth hormone is effective in correcting linear
growth disorders in CKD children. This can be seen
from the increase in height from eight studies as well
as significant differences between the therapy group
and the control group. 14,15,17,18,19,20,21,22,23,24 In
children who were intervened with growth hormone
for 1 year, the results were found to be effective in
increasing height in all studies. 14,15,18,23 A study
conducted on thirty prepubertal CKD children, it was
found that the height of the intervention children
increased by 0.98 standard deviations (SD), inversely
proportional to the unintervened group, the height
decreased by 1.02 SD . This study is the best result
of all studies conducted for 1 year.18
In addition to height in SD units, linear growth
can also be assessed from high speed. An ak PGK who
intervened, high-speed increase of 3.6 cm / year, with
an increase of 3.2 cm greater than the control group.
14 Response to growth hormone administration was
also effective in increasing height during 2 years of
treatment in all studies. 17,19,20,22 The best study
results showed an increase in the height of CKD
children in the therapy group reaching 1.39 SD, while
in the control group it decreased by 0.07 SD.22
There are two studies where there is a significant
increase in height in the treatment group, but there
is no significant difference when compared to the
control group. These results were obtained in the
research of Hertel et al. and Mencarrelli et al. 20,23 In
Hertel et al's study, there may be no significant
difference, because the control group taken was the
group that was still given a lower dose of growth
hormone, namely 2 IU/m²/day , while the therapy
group was 4 IU/m²/day, so that the hormone This
low dose growth rate still has an effect on the height
of CKD children.23 The Mencarelli et al study, which
was conducted on infants with CKD or with end-stage
renal disease (ESRD) who had received growth
hormone before 1 year of age, probably did not show
a significant difference in infant height between the
treatment and control groups. , because in addition
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to giving growth hormone, nutritional intake of
infants was also considered in both groups. 20
Adequate nutritional intake is the most important
factor for achieving normal growth and body
composition in infants with CKD. Growth hormone
can be used as a secondary treatment in CKD infants.
If the baby receives growth hormone therapy, it is
recommended that it be followed by adequate
nutrition, so that the effect of growth hormone
therapy is more optimal. 29
During puberty, the height increase of CKD
children is not as good as that of normal children,
due to the fact that in CKD children the growth
acceleration process is delayed and shortened, so
that the use of puberty is not optimal.30 In the
literature review that has been carried out, there are
no studies that specialize in research on pubertal
children. However, there is one study that compared
the increase in height of CKD children with growth
hormone intervention during prepubertal and
pubertal periods. This study was a cohort study (5
years), which showed that the increase in height in
CKD children who were intervened with growth
hormone in the prepubertal period was better than
during puberty. 21
CKD children receiving dialysis therapy had worse
growth retardation than CKD children without
dialysis, although growth rates increased after
transplantation.31 Research in children who received
kidney transplants, found a good response to the
administration of growth hormone. The ratio of
children's height given the intervention also
increased significantly from the children without
intervention, and the administration of growth
hormone did not affect the condition of the
transplanted kidney.14,15 However, when this study is
compared with other studies, it appears that studies
devoted to children who received transplants showed
that the increase in average height was not as good
as the others.
The most important height result is final height or
adult height. Data on CKD children who were given
growth hormone for 5 years and followed until they
reached their final adult height showed that CKD
children who were intervened had maintained the
process of pursuing growth, while CKD children who
did not receive therapy experienced progressive
growth failure. Final adult height in intervention
children was -1.6 1.2 SD and -2.1 1.2 SD in children
without intervention. 21
Dosage, Frequency, Method of Administration,
and Duration of Administration of Growth Hormone
in CKD Children The results of the RCT reviews that
have been carried out give the impression that CKD
children should be given growth hormone at a dose of
4 IU/m²/day, because many studies have conducted
experiments with this dose. 14,15,16,17,19,20,22,23 Doses
of 4 IU/m²/day are considered more effective in
increasing height than doses of 2 IU/m²/day. In
children who were intervened with growth hormone 2
IU/m²/day for 2 years, the increase in height that
balanced the dose of 4 IU /m²/day was only in the
first 6 months, then 1.5 years after that the process
of pursuing growth stopped. Height velocity increased
from -3.6 SD to 2.3 SD at intervention 4 IU/m²/day
and at intervention 2 IU/m²/day increased from -2.7
SD to 0.4 SD. There was a 2.8 SD greater difference
in the high-speed increase at a dose of 4 IU/m²/day.
19 This conclusion was drawn based on seven
studies. This is because the study did not show
significant differences in larger doses, da n two other
studies to show that the dose with a different unit IU
/ kg / week and IU / m 2 / week. 18,21,23
The frequency and method of administration of
growth hormone in all studies were the same, namely
once a day and given by subcutaneous injection. The
duration of administration of growth hormone varies,
some are researched for 6 months, some are 5 years,
and the most are 1 year and 2 years. There was no
effect of duration of administration on the magnitude
of the difference in height between the therapy and
control groups. 14,15,16,17,1 8,19,20,21,22,23
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In several reviews, there is a pattern that shows
the effect of growth hormone begins to fade with a
longer duration of treatment. 18,19,20,22 For example,
the increase in height of CKD children who received
growth hormone for the first six months was 0.57 SD,
0.41 SD for the second six months, and 0.15 SD for
the third six months, and 0, 08 SD for the last six
months. 18 The time dependence of the effectiveness
of this growth hormone cannot be concluded with
certainty, because not all data are supportive and
sufficient to draw conclusions. So, determining how
long to give growth hormone is recommended by
evaluating the patient's height every 6 months.
Safety of Giving Growth Hormone to CKD
Children
1. Kidney
The metabolic products of growth hormone,
namely growth hormone, growth hormone receptors,
IGF-1 and IGF-1 receptors are expressed in kidney
tissue. 32 Under normal circumstances, most of the
metabolic by-products of this growth hormone are
cleared in the kidney, taking advantage of efficient
glomerular filtration and extensive degradation by the
kidney. 33 In children with CKD there is a decrease
in glomerular filtration rate (GFR), which led to the
disruption of the metabolic excretion of growth
hormone. This disorder may affect or aggravate the
condition of the kidneys. 32
The safety of growth hormone on the kidneys can
be seen by assessing kidney function, namely from
serum creatinine, inulin clearance , creatinine
clearance and GFR. Inulin and creatinine can be used
as a basis for assessing GFR because almost all of
them are excreted in the kidneys. 33 In the review
that has been carried out, there are five studies that
show no significant change in the value of the kidney
function. 15,17,18,22,23 Emp at the study did not
address the results of the kidney function.
16,19,20,21 One study showed an increase in serum
creatinine followed by a decrease in inulin clearance
, but the difference was not significant between the
treatment and control groups.14 However, the results
of this study cannot be concluded, because the
increase in serum creatinine is not only caused by
impaired excretion of creatinine through urine, but
can also be caused by an increase in creatinine
production. In CKD children who receive growth
hormone, there can be an increase in muscle mass so
that muscle metabolism that produces creatinine
also increases.34
2. Other Organs
Side effects of giving growth hormone in other
organs in the study of Guest et al for 1 year, one
patient had papilledema, without symptoms of
benign intracranial hypertension (BIH).21
Papilloedema is swelling of the optic nerve due to
increased intracranial pressure.35 The diagnosis in
this study was made on the basis of routine
ophthalmologic examinations, where papilledema
resolved after discontinuation of growth hormone
therapy. Even so, it cannot be concluded that growth
hormone causes abnormalities in the eye. 21 Another
non-RCT study, which followed 30 patients who
received growth hormone and underwent routine eye
examinations, found no eye abnormalities in the
children studied.36
3. Parathyroid Hormone
The effect of growth hormone on parathyroid
hormone is still uncertain. The indirect effect of
growth hormone is on the excretion of phosphate.
Growth hormone has antiphosphaturic properties, so
it can increase phosphate levels in the body.
Increased phosphate in the body, stimulates
parathyroid hormone to work to inhibit reabsorption
of phosphate in the kidneys.37 Studies Guest et al and
Mencarrelli et al, showed that parathyroid hormone
increased in the treatment group, but the increase
was not significant.14.20
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Parathyroid hormone acts on the kidneys by
inhibiting the reabsorption of phosphate and
stimulating calcium reabsorption in the kidneys. In
addition, parathyroid hormone also works indirectly
by stimulating the 1 hydroxylase enzyme in the
kidneys which is responsible for the formation of
active vitamin D3. Vitamin D3 can increase calcium
absorption in the small intestine. With this way of
working, a slight increase in parathyroid hormone
cannot be said to be a problem in a person's body. 38
However, an excessive increase in parathyroid
hormone is also a sign of kidney disorders.39
Effect of Growth Hormone on Bone Density in
CKD Children
The normal bone replacement process
consists of two processes, namely bone formation and
bone resorption.40 Growth hormone is one that
affects the process of bone formation. Growth
hormone directly and indirectly (via IGF-1) stimulates
osteoblastogenesis and chondrogenesis.41
Osteoblasts play an important role in bone formation.
Osteoblasts are mononuclear cells that attach to the
surface of bones and form new bone. The products
produced by osteoblasts are called bone formation
markers. Alkaline phosphatase (AP) is one of the
markers of bone formation, which is an enzyme to
prepare an alkaline atmosphere in the formed osteoid
tissue, so that calcium can be easily deposited in that
tissue.42,43 AP in serum comes from liver, bone,
intestine, spleen, kidney and placenta. 42 During
childhood and adolescence, bone-derived AP
predominates and accounts for up to 90% of total
serum AP. 44 In the absence of liver disease and liver
enzyme results within normal limits, the increase in
serum AP was considered to represent bone-specific
AP.45 In this review of RCTs, three studies assessed
serum AP and found a significant increase in serum
AP in the growth hormone-treated group. 16,19,22
In addition to AP, osteocalcin is also a marker of
bone formation. Osteocalcin plays an important role
in bone, namely the process of mineralization and the
process of calcium ion homeostasis. Osteocalcin
examination is a good parameter to determine
disorders of bone metabolism during bone formation
and bone replacement.45 Low osteocalcin is
associated with an increased risk of fracture.42
Testing of osteocalcin is often used as a biomarker of
bone-forming drugs and to assess the effectiveness of
treatment outcomes. 45 In this review, there was a
study that tested for osteocalcin and there was a
significant increase in serum osteocalcin in the
growth hormone-treated group. 22
5. Conclusion
Giving growth hormone is effective in
improving the child's height PGK, and the dose
should be given is 4 IU / m 2 / day, 1x daily, by
subcutaneous injection and duration of
administration varies depending on response to
therapy. Administration of growth hormone does not
aggravate kidney disorders in children with CKD.
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