International Journal of Nephrology and Renovascular Disease Dovepress

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REVIEW

Factors Affecting Neurocognitive Function

in Children with Chronic Kidney Disease:
A Systematic Review
Elrika A Wijaya, Purboyo Solek, Dzulfikar DL Hakim, Rini Rossanti, Ahmedz Widiasta , Dany Hilmanto
Department of Child Health, Faculty of Medicine, Universitas Padjadjaran/Dr. Hasan Sadikin General Hospital, Bandung, West Java, Indonesia

Correspondence: Dany Hilmanto, Tel +628122266879, Email [email protected]

Purpose: In children, chronic kidney disease (CKD) has been known to affect neurocognitive function which can impair the quality
of life. This study aims to determine the factors and treatment modalities which might affect neurocognitive function in pediatric
population with CKD.
Patients and Methods: A systematic review was done using 3 electronic databases: PubMed, ScienceDirect, SpringerLink, and
carried out based on PRISMA guidelines. Our review included articles published in the last 10 years (2011–2021) in English, on
children aged 0–18 years with CKD. Factors affecting the children’s neurocognitive function were assessed.
Results: Eight articles were included in this study. Three articles reported that parent’s education, especially maternal education affect the
neurocognitive function of children with CKD. In relation with modalities, in general, children with CKD who had kidney transplant had
a better neurocognitive outcome. A longer duration of hemodialysis (HD) was associated with poorer neurocognitive outcomes. Other
factors that can affect the neurocognitive function included depression, a history of abnormal births, seizures, and hypertension.
Conclusion: In children, CKD might cause neurocognitive function disorders through various complex and interconnected mechan­
isms. Further studies are needed to determine the mechanism and prevention of neurocognitive disorders, as well as the best choice of
therapeutic modality to improve both kidney function and neurocognitive function in children with CKD.
Keywords: chronic kidney disease, neurocognitive function, children

Introduction
Chronic kidney disease (CKD) is an irreversible kidney disorder, anatomically and functionally.1 In general, the
prevalence of CKD is about 18 patients out of 1 million children.2 Based on data from a large study by the ItalKid
Project from a population-based register in Italy, consisting of children and young adult population less than 20 years of
age, the incidence of CKD is 12.1 cases and the prevalence is 74.7 cases out of 1 million population of people younger
than 20 years old. This study also found that CKD in the pediatric population is mostly caused by hypoplasia and
dysplasia, with or without other malformations of the urogenital system.3,4 Other kidney diseases might also cause CKD,
such as nephrotic syndrome or glomerulonephritis, urinary obstruction or infection.5
In children, chronic kidney disease has been known to affect neurocognitive function due to uremia and anemia, especially
in stage five, which can affect brain metabolism, myelination of neurons and synapse development.6 The results of the studies
regarding this topic varied from one study to another. Several studies found a lower Intelligence Quotient (IQ) in children with
CKD compared to the healthy group. Another study showed no significant differences in memory (verbal and non-verbal)
function in children with and without CKD. Other studies had stated that there were deficits in auditory assessment, verbal
working memory, and emotional recognition. Intelligence Quotient scores in children who had chronic hemodialysis (HD)
were lower than in children with moderate CKD or children who had kidney transplantation.6
Many interventions had been carried out to prevent further decline in kidney function in children with CKD. In addition
to providing conservative therapy at an early stage, renal replacement therapy (RRT), including hemodialysis (HD),

International Journal of Nephrology and Renovascular Disease 2022:15 277–288 277

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peritoneal dialysis (PD), and kidney transplantation, are some of the modalities that can be performed in children with stage
five CKD (terminal renal failure). One study found that health-related quality of life (HRQOL) was better in children with
CKD with kidney transplantation than PD and HD.7 It is known that neurocognitive function is one of many components that
can affect a person’s Health-Related Quality of Life (HRQoL); thus, neurocognitive function can be affected indirectly by the
therapeutic modality given to the patient.8,9 In patients with CKD undergoing dialysis, the prevalence of neurocognitive
disorders ranges from 30% to 70%. In general, 30% of patients with CKD had poor cognitive performance scores (about one
standard deviation lower than the control group), with 18% having memory deficits and 30% having executive function
deficits.10 This is particularly important in the children, because the brain still developed rapidly. On the other hand, impaired
neurocognitive function can affect the quality of life of children in the future.
This systematic review was made to find out about factors that can affect neurocognitive function in children with
CKD. Hopefully, through this study, we can provide a deeper description and understanding of the relationship between
CKD and neurocognitive function in children with CKD.

Materials and Methods

Search Strategy
Literature search was performed using keywords with a combination of Boolean connectors (“CHILDREN” OR
“PEDIATRIC”) AND (“END STAGE RENAL DISEASE” OR “CHRONIC KIDNEY DISEASE” OR “CKD” OR
“ESRD” OR “ESKD”) AND (“NEUROCOGNITIVE”) AND (“RENAL TRANSPLANT” OR “KIDNEY
TRANSPLANT” OR “HEMODIALYSIS” OR “PERITONEAL DIALYSIS” OR “RENAL REPLACEMENT
THERAPY”) with various combinations. The systematic review was carried out based on the Preferred Reporting
Items for Systematic Review and Meta-Analysis (PRISMA) guidelines. The authors used articles from 3 databases:
PubMed, ScienceDirect, and SpringerLink. The population of children with CKD and the therapeutic modalities were
assessed. The systematic review also assessed factors influencing neurocognitive function in children with CKD.

Eligibility Criteria
The studies included were limited to articles published in the last 10 years (2011–2021), in English, included children
aged 0–18 years with CKD who were treated either conservatively or with RRT, and whose neurocognitive function was
assessed. The exclusion criteria were researches using qualitative methods, abstracts from national/international con­
ferences, guidelines, case reports, commentaries, and review articles.

Data Extraction
The data was extracted from the literatures which met the aforementioned criteria. For continuous variables, the number
and percentage of variables were assessed. The findings were also described further in narratives. Some findings in the
form of categorical variables were described in numbers. The main outcomes assessed were impaired neurocognitive
function in children with CKD, the therapeutic modalities used, and factors that might affect neurocognitive function in
children with CKD.

Data Analysis
All studies which met the criteria were identified using the selected keywords. Then, title screening was done, followed
by abstract screening. Complete article screening was done studies that met the inclusion criteria and did not meet the
exclusion criteria.

Study Quality
The validity of the included studies was assessed using the Critical Appraisal Skills Program (CASP) tool for the cohort
studies and Center for Evidence Based Management (CEBMa) for the cross sectional studies.11,12 These tools consisted
of several checklist based on the research methods used and were used to assess the trustworthiness, relevance, and
results of the published papers.

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Results
Based on PRISMA guidelines, the article review process is illustrated in Figure 1. From the search results, 561 articles
were found after articles and duplicated titles were removed from the online database, consisted of 412 articles from
PubMed, 51 articles from ScienceDirect, and 98 articles from SpringerLink. After screening the titles and abstracts of the
articles, there were 14 articles, and after full article review was done, eight articles that met the criteria were obtained.
Two articles were literature reviews, five did not contain the required data, and one did not use children as the sample in
their research. The search results article findings are summarized in Table 1.
From this study, we found that several factors that affect the neurocognitive function of children with CKD include
the parent’s education, especially maternal education in the study of Zyada et al,13 Kogon et al,14 and Molnar-Varga
et al.15 In relation with the modalities, studies from Johnson et al,16 and Molnar-Varga et al15 showed that in general,
children with CKD children with kidney transplantation had a better neurocognitive outcome. In children with CKD,
a longer duration of HD was also found to be associated with poorer neurocognitive outcomes in a study by Popel et al,17
Zyada et al,13 and Molnar-Varga et al.15 In a control study, patients with renal impairment showed poorer neurocognitive
function than normal children by Zyada et al,13 Johnson et al,16 and Molnar-Varga et al15 Several factors that can affect
the neurocognitive function of children with CKD include depression, history of abnormal births, seizures, and
hypertension. From all included studies, it was found that the neurocognitive function domains which affected by
CKD varied, but generally, the affected domains were attention, visual-spatial, visual working memory, verbal function,
and executive function. The number of the boys was higher in the entire group of patients with CKD when compared to
the number of the girls.13–20
The stages of CKD in the included articles in this systematic review were CKD stages 1–4, dominated by CKD stage
5 patients.

Figure 1 Journal article search flowchart.

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Table 1 Summary of Journal Findings
The Research Result CKD Theurapeutic Neurocognitive Sample Research Research Country Year Researcher Title
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Stage Modalities Assessment Methods Sites Methods

● School performance was Stage V HD Wechsler Intelligence Scale 60 Egypt Cross Egypt 2017 Zyada et al11 Assessment of
worse in the HD group Kidney for Children Third Edition children Sectional cognitive
than the post-kidney Transplant (WISC III) aged 6–16 functions in
transplant group and the years children on
control group. regular
● There was a negative cor­ hemodialysis and
relation in the HD group after renal
between the duration of transplantation11
HD and the WISC III
subtest scores,
● There is a positive corre­
lation between post-
kidney transplant dura­
tion and WISC III subtest
scores
● Low educated parents
were more in the post-
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kidney transplant group

(60%) than in the trans­
plant group (25%), and
the control group (5%)

● Longer dialysis duration is Stage V Peritoneal Wechsler Preschool and 15 Canada Prospective Canada 2019 Popel et al15 Neurocognitive
associated with worse dialysis in 11 Primary Scales of patients (Alberta) Cohort (Alberta) and functional
outcome patients Intelligence–3rd edition who outcomes at 5
● HD is associated with HD continued Beery- Buktenica received years of age
poorer developmental with PD in 4 Developmental Test of transplant after renal
outcome patients Visual-Motor Integration before the transplant in
● Age at transplantation is Followed by (VMI; 5th edition) age of 5 early
not significantly asso­ kidney years childhood15
ciated with neurologic transplant in all
outcome patients
● Neurocognitive outcome

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is better than data in the
past 2–3 decades.

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Depression in patients with Stage I–IV Conventional Wechsler’s Abbreviated 1 CKD United States Cross United States 2019 Kogon Depression and
CKD shows that there are Srage V 51 patients Scales of Intelligence patients (Philadelphia) Sectional (Philadelphia) et al12 neurocognitive
functions that are affected HD (WASI) and 64 dysfunction in
by neurocognitive 2 patients Conner’s Continuous controls pediatric and
examination in the domains Transplant 18 Performance Test II (CPT aged 8–25 young adult
of attention, visual memory, patients II) years chronic kidney
visual-spatial, visual working Wechsler Intelligence Scale disease.12
memory, problem solving. IV (WISC IV)
Wechsler Memory Scale
Third Edition (WMS III)
Delis Kaplan Executive
Function System (D-KEFS)
Behaviour Rating Inventory
of Executive Function
(BRIEF)

● Abnormal birth history Stage I–V NA Wechsler’s Abbreviated 124 United States Prospective United States 2016 Hooper Neurocognitive,
and low maternal educa­ Scales of Wechsler preschool (Philadelphia, Cohort (Philadelphia, et al16 social-
tion are significantly asso­ Preschool and Primary children Kansas) Kansas) behavioral, and
ciated with lower IQ Scale of Intelligence-Third with CKD adaptive
● History of seizures Edition (WPPSI III) functioning in
related to worse execu­ Kiddie Conners’ preschool
tive function Continuous Performance children with
Test for ages 48–71 mild to
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months (K-CPT) moderate kidney

disease.16

(Continued)
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Table 1 (Continued).

The Research Result CKD Theurapeutic Neurocognitive Sample Research Research Country Year Researcher Title
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Stage Modalities Assessment Methods Sites Methods

● FSIQ, academic function, Stage V PD in all Wechsler Intelligence Scale 12 United States Cross United States 2013 Johnson Long-term
and executive function patients at early for Children Fourth Edition patients Sectional et al14 neurocognitive
are lower than the con­ treatment, then (WISC-IV) with ESRD outcomes of
trol group 2 patients Wechsler Individual in the first patients with
● Shorter duration of dialy­ changed to HD Achievement Test Second 16 months end-stage renal
sis and younger age at Edition—Abbreviated disease during
transplant are associated (WIAT-II- A) infancy.14
with better outcomes in Wide Range Assessment of
executive function, mem­ Memory and Learning,
ory, and academic Second Edition (WRAML2)
achievement Behavior Rating of
Executive Functioning
(BRIEF)

● The group with CKD had Stage II–V Conventional NA 162 United States Cross United States 2015 Ruebner Neurocognitive
lower scores in all neu­ Hemodialysis There are 11 domains patients (Philadelphia) Sectional (Philadelphia) et al17 dysfunction in
rocognitive domains, with Kidney assessed: attention, aged 8–25 children,
statistically significant Transplant language, verbal memory, years adolescents, and
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domains were attention, verbal working memory, young adults

memory (including verbal, visual memory, visual with CKD.17
visual, short-term mem­ spatial, visual working
ory, working memory), memory, executive
visual spatial, inhibitory function, inhibitory
control function, problem solving,
● Neurocognitive perfor­ set shift
mance was better in
patients with higher
eGFR, with significant dif­
ferences in the domains
of attention, visual spatial,
visual working memory
● Higher blood pressure is
associated with poorer

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● The duration of CKD NA Conventional Conner’s Continuous 340 North Cross North 2015 Mendley Duration of
affects the executive Performance Test II (CPT- children America Sectional America et al18 chronic kidney
function of the inhibitory II) aged 6–21 disease reduces
domain and Delis-Kaplan Executive years attention and
concentration Function System Tower executive
● Higher family income and Task (DKEFS) function in
better maternal education Wechsler Intelligence Scale pediatric
showed better working for Children Fourth Edition patients.18
memory component (WISC IV)
assessment results

● Transplant patients, com­ Stage V Kidney Woodcock-Johnson 35 Hungary Cross Hungary 2016 Molnar- Neurocognitive
pared to controls, have Transplant Cognitive Ability Test – children Sectional Varga et al13 functions of
lower IQs in all aspects, International Edition aged 6–18 pediatric kidney
and have better scores on (WJIE) years who transplant
verbal skills, with the received recipients.13
lowest skill on cognitive kidney
efficiency. transplants
● Younger age at started
dialysis and longer cumu­
lative dialysis time asso­
ciated with poorer
neurocognitive outcome
in children
● Higher maternal educa­
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tion is associated with

Woodcock-Johnson
Cognitive Ability Test –
International Edition
(WJIE) scores
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In a study by Ruebner et al, lower stage of CKD or those with higher Glomerular Filtration Rate (GFR) had an effect
on better neurocognitive function in patients with CKD.16
In the study of Popel et al, it was found that although the overall neurocognitive outcome in patients with CKD was
not good, in that study, the neurocognitive outcome of children with CKD was better than 2–3 decades ago. This might
be related to the development of therapeutic modalities for children with CKD.17

Discussion
According to Kidney Disease Improving Global Outcome (KDIGO), the definition of CKD is an abnormality of kidney
structure or function that lasts for more than three months, with implications for the patient’s health. CKD is classified by
the etiology, GFR category, and albuminuria category.17 Based on the Kidney Disease Outcomes Quality Initiative
(KDOQI), CKD can be defined as kidney disease with one of the following two criteria, namely (1) kidney damage for at
least three months with or without decreased glomerular filtration rate (GFR), or (2) patients with GFR less than 60 mL/
min/1.73 m2 for three months with or without renal impairment. However, there are two exceptions in children. The
minimum three-month criteria for the first criterion does not apply if the child has persistent kidney damage. The second
criterion does not apply to children <2 years of age because GFR <60 mL/min/1.73m2 can be considered normal due to
suboptimal kidney function in children this age. In children, chronic kidney disease can cause many implications, such as
failure to thrive, electrolyte disturbances, anemia, decreased quality of life, and impaired neurocognitive function.1
Neurocognitive function decline in children with CKD is caused by various factors that may be interrelated. Several
domains which consistently affected by CKD from several studies included in this systematic review were attention,
visual-spatial, visual working memory, verbal function, and executive function. The presence of attention disorder could
affect a child’s ability to acquire new abilities and perform previously learned abilities. These attention disturbances may
affect other neurocognitive domains, such as memory and verbal function.21
There were several clinical biomarkers which had been known to affect neurocognitive function from previous studies
in children with CKD. Elevated blood pressure was associated with lower full scale IQ (FSIQ) and set shifting error in
executive function. Anemia, proteinuria, longer duration of CKD, lower GFR and some certain genomic variants were
also associated with lower IQ in children. More interestingly, correlation between neuroimaging studies and cognitive
function in children with CKD was also found in a recent study. Using CT imaging, global cerebral atrophy, silent white
matter infarcts, lower cerebral density, and ventriculomegaly were found more in children with CKD compared to normal
children. When the imaging was done using Functional Magnetic Resonance Imaging Study, cerebral blood flow to the
brain was also found to be disrupted, and this might be the one of the complex mechanisms that underlay the cognitive
function decline in children with CKD.22
In one of the articles included in this systematic review, Kogon et al found that depression was one of the factors that
affect neurocognitive function in children with CKD. This finding is in line with another finding in a systematic review
by Baune et al conducted on a general population of adolescents and young adults where depression was associated with
the domains of executive function, verbal, and visual memory.23
The included studies found that high blood pressure in patients with CKD would affect their neurocognitive function.
Hypertension could cause and became a marker of CKD severity in children. It was also found to increase the risk factor
for cardiovascular disorders in the future. In patients with CKD, the pathophysiological mechanism of hypertension was
due to abnormal vascular regulation in conditions of fluid overload, increased cardiac output, and increased peripheral
vascular resistance. The activation of the renin-angiotensin-aldosterone system (RAAS), possibly due to renal tissue
damage with hypoperfused areas could cause vasoconstriction, water and salt retention, and sympathetic nerve
hyperactivity.24 Although the physiological basis for decreased neurocognitive performance in children with hyperten­
sion was unclear, there was evidence of changes in cerebrovascular reactivity in children. Cerebrovascular reactivity was
an important physiological mechanism for maintaining constant blood pressure and was defined as the capacity of
cerebral blood vessels to dilate or constrict to different stimulation. In addition, cerebrovascular reactivity was an
important biomarker of brain vascular reservoir. Hypertension might affect small blood vessels, then cause vascular
remodelling and disturbances in the regulation of cerebral blood flow. Cognitive processes stimulate the regional
distribution of blood flow, providing metabolic support to active neural regions. Hypertensive conditions might interfere

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with this normal blood flow distribution and might also reduce the ability to increase blood flow in response to increased
neuronal activity, known as the vascular hypothesis of cognitive dysfunction. This process might underlie the occurrence
of impaired cognitive function in individuals with hypertension. This study result is in line with other studies by Lande
et al, and Ostrovskaya et al, regarding hypertension in children, which showed that a decrease in executive function was
associated with impaired cerebrovascular reactivity.25,26
The accumulation of toxic urea in neurons is also a factor that may cause neurocognitive disorders, seizures, and
status epilepticus in patients with CKD. An animal study by Mazumder et al showed that there was an accumulation of
Guanidinosuccinic acid in CKD patients and an increase in adenine which then caused clonic seizures, status epilepticus,
and hippocampal neurons damage. In addition, electrolyte imbalance in the brain and peripheral nerves can cause
neurotransmission disturbances, which indirectly indicates that seizures could be a marker of brain damage and resulted
in impaired neurocognitive function in patients with CKD.27 In CKD, it was also found that the blood–brain barrier will
change and become more permeable, so that harmful components could enter the brain more easily. Blood–brain barrier
damage was partly mediated by systemic inflammation, which is one of the causes of CKD. In systemic inflammatory
conditions, cytokines and chemokines, including interleukins will enter brain tissue and cause neuronal and astrocyte
damage. Uremic conditions could also cause damage to the blood–brain barrier. Increased urea to a particular concentra­
tion could damage the tight junction epithelium in the intestine and the blood–brain barrier, leading toxic materials
entering the blood vessels. Uremia was also associated with the emergence of oxidative stress. It could cause conversion
from nitric oxide to toxic peroxynitrite, and afterwards, lipid peroxidation and neuronal damage. In animal experiments,
pyknosis and apoptosis were found in hippocampal neurons under uremic conditions. Decreased renal homocysteine
clearance in CKD could cause an increase in homocysteine, and its conversion to homocysteic acid would activate of the
N-Methyl-D-Asparate receptor, causing neuronal toxicity. Homocysteic acid might also cause endothelial dysfunction
and a pro-thrombotic effect. Impaired clearance of drugs consumed due to kidney damage and increased penetration into
the blood–brain barrier are also factors that play a role in neurotoxicity and cognitive decline in CKD.28
In patients with CKD, it is known that the occurrence of fibrosis in the renal interstitium caused changes in the
extracellular matrix (ECM) which then changed the structure of the kidney. The primary mechanism leading to the
accumulation of ECM deposition is found to be the proliferation and activation of interstitial fibroblasts to myofibroblasts
and increased ECM synthesis and release. Erythropoietin (EPO) production would be affected, and this mechanism is
essential in the disturbance of hematopoiesis process. Production of EPO occurs interstitially in fibroblast-like cells in the
renal cortex and medulla. In CKD, cells that produce EPO will experience progressive damage, accompanied by fibrosis
in the patient’s kidneys leading to anemia.29 In a study by Agrawal et al, a decline in cognitive function in adult patients
with anemia was found. In addition, cognitive function was also associated with hemoglobin levels in adult patients who
previously had an intact neurocognitive function. This may be related to a decrease in the number of red blood cells and
oxygen-carrying capacity, which impairs neurocognitive function.
Low birth weight (LBW), prematurity, and growth disorders are markers of disturbances in the intrauterine environ­
ment. There is a correlation between birth weight and the number of glomeruli, density, volume, size, and filtration rate in
the kidney after birth. The number of nephrons and birth weight were also found to be related with increased blood
pressure and later in life, the occurrence of CKD.30 In conditions where the number of nephrons is reduced, a person will
initially be able to maintain a normal GFR. The size of the nephrons will enlarge to increase the surface area necessary
for the kidneys to work. Overtime, this adaptive response will become harmful. An increase in the surface of the
glomerulus will cause sodium retention and systemic hypertension, and glomerular hyperfiltration will interfere with the
autoregulatory mechanism of the kidney, causing intraglomerular hypertension and proteinuria. This process will cause
the nephrons to become sclerotic and lead to a decrease in the number of nephrons and an even more severe
hyperfiltration process in the remaining nephron causing more nephron damage and kidney damage in a repeated
cycle. In premature infants, developing nephrons are susceptible to maldevelopment and dysfunction in the extrauterine.
Premature infants are found to have reduced nephron width and more mature-looking glomeruli than normal infants,
indicating that nephrogenesis had stopped or post-natal maturation was faster than term infants. Premature infants also
have a larger glomerular volume (indicating a glomerular hyperfiltration process), and approximately 13% of their
glomerulus have abnormal histology, with dilated Bowman’s space and less glomerular tuft.31

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As described in the previous paragraph, the mechanism that causes neurocognitive disorders in patients with CKD
who have a history of low birth weight or prematurity may be due to hypertension and uremia. However, the condition of
low birth weight and prematurity itself can cause neurocognitive disorders. Lower IQ scores in children with LBW were
associated with structural changes in the brain compared to children who born with normal birth weight in a study by
Sripada et al32 Another study by Joseph et al showed a decrease in neurocognitive function in infants born with
extremely low birth weight and gestational age <28 weeks, where neurocognitive deficits was found in ten years old
children, and this finding supported the previous study.33
There is a risk of brain structural abnormalities and neurocognitive disorders in patients undergoing dialysis. Structural
abnormalities include brain atrophy, silent brain infarction, white matter hyperintensity, and leukoaraiosis (subcortical injury
to white matter due to loss of axons and myelin secondary to ischemic injury). Some factors that are thought to cause this
include rapid changes in blood pressure during dialysis. Autoregulatory mechanism which is disrupted due to vascular
disorders in hypertensive conditions in CKD patients can cause intradialysis hypertension.34 In a study by Sandwijk et al, it
was found that through MRI a year after transplantation, there was an increase in the volume of white matter in the brain and an
improvement in neurocognitive function. The volume of white matter was found to increase due to the movement of water
from extracellular to intracellular. The pathophysiology of this process was still unclear. In CKD, there are osmotic changes in
the brain due to uremic accumulation and water retention. Under normal conditions, the brain can maintain a constant
intracellular volume by adapting to osmotic pressure. However, in chronic inflammatory triggered by uremic toxins, there is
cellular dysfunction and increased cellular permeability, leading to reduced intracellular volume in patients with CKD.35 The
finding of improved neurocognitive function in children with CKD who underwent transplantation compared with patients
who had HD was in line with findings in adults. In a study by Posselt et al, who assessed neurocognitive function in adult
patients with CKD who received transplants versus with adult patients receiving hemodialysis, it was found that neurocog­
nitive function was better in several domains in adult patients who received kidney transplantation. This may also be due to
improved post-transplant endocrine and exocrine function restoration, where potassium, phosphate, and calcium values
become normal over time.36

Study Limitations
As the limitation of this study, currently, studies regarding the association between CKD with neurocognitive function in
children are still limited, especially regarding the relationship between neurocognitive function and the therapeutic
modality. The diversity of age ranges and the use of various neurocognitive examination methods can cause the results to
be less specific, since every method to measure neurocognitive examination has different sensitivity and specificity. Each
method might also measure different domain of neurocognitive with different method for different age range, and this
might also affect the result. In the future, perhaps a similar systematic review study, which included more studies with
more homogeneous age range samples and uniform assessment tools, can be done to draw more precise and detailed
conclusions regarding neurocognitive function in children with CKD.

Conclusion
In children, CKD can cause neurocognitive function disorders through various complex and interconnected mechanisms,
and affected by several factors, such as neurocognitive function disorders, including the education of parents, especially
the mother’s educational level, the therapeutic modalities used, the presence of depression, history of abnormal births,
history of seizures, and hypertension. Treatment modality used might also affect the children’s neurocognitive function.
Children who underwent kidney transplant generally had better neurocognitive function compared to children who had
other treatment modalities. In children with CKD, the generally impaired domains include attention, visual-spatial, visual
working memory, verbal function, and executive function.

Acknowledgment
The authors thank Universitas Padjadjaran for the financial help granted in publishing this article.

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Disclosure
The authors report no conflicts of interest in this work.

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