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Saudi Journal of Kidney Diseases and Transplantation
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Table of Contents   
ORIGINAL ARTICLE  
Year : 2020  |  Volume : 31  |  Issue : 2  |  Page : 395-406
Assessment of cognitive functions and adaptive behavior in children with end-stage renal disease on regular hemodialysis


1 Department of Pediatrics, Faculty of Medicine, Tanta University, Tanta, Gharbia Governate, Egypt
2 Department of Neuropsychiatry, Faculty of Medicine, Tanta University, Tanta, Gharbia Governate, Egypt

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Date of Submission30-Oct-2018
Date of Decision11-Dec-2018
Date of Acceptance16-Dec-2018
Date of Web Publication09-May-2020
 

   Abstract 


Chronic kidney disease (CKD) is defined by the Kidney Disease and Outcome Quality Initiative as a child who has kidney damage lasting for at least three months with or without decreased glomerular filtration rate. Hemodialysis (HD) means removal of waste products and extra fluid directly from the blood when the kidneys do not work properly. Studies aimed at investigating neurocognitive impairment in children with CKD have identified a wide range of delays in cognitive development. The aim of this study was to assess the cognitive functions and adaptive behavior in children with end-stage renal disease (ESRD) on regular HD. This case-controlled study was conducted on 30 children suffering from ESRD who were on treatment at the Pediatric Nephrology Unit of Tanta University Hospital. Thirty apparently healthy children served as a control group, in the period from January 2017 to January 2018. All children were subjected to full history taking, careful physical and neurological examination, specific investigations including assessment of intelligence quotient (IQ) using Stanford Binet test 5th edition; assessment of adaptive behavior, assessment of executive functions by using Wisconsin Card Sorting Test; and continuous performance test. This study showed that mean values of IQ and the Vineland test were significantly lower among patients than controls. The study suggests that children with ESRD had lower IQ, adaptive behavior and executive functions than healthy control children.

How to cite this article:
Al Shahawy AK, El-Gamasy MA, Elhakeem Seleem MA, Mawlana W, El Sharkaway AH. Assessment of cognitive functions and adaptive behavior in children with end-stage renal disease on regular hemodialysis. Saudi J Kidney Dis Transpl 2020;31:395-406

How to cite this URL:
Al Shahawy AK, El-Gamasy MA, Elhakeem Seleem MA, Mawlana W, El Sharkaway AH. Assessment of cognitive functions and adaptive behavior in children with end-stage renal disease on regular hemodialysis. Saudi J Kidney Dis Transpl [serial online] 2020 [cited 2020 Jul 3];31:395-406. Available from: http://www.sjkdt.org/text.asp?2020/31/2/395/284014



   Introduction Top


Chronic kidney disease (CKD) is defined as slow and progressive deterioration of kidney function that is typically irreversible.[1] It is used to describe the whole continuum of progressive kidney disease ranging from chronic renal insufficiency (CRI) to end-stage renal disease (ESRD). The severity of CKD is defined by a decrement in glomerular filtration rate persisting for three or more months.[2]

Advances in medical care, including improvements in dialysis and transplantation, have increased the survival rates for children with ESRD. However, it is clear that this chronic disease has adverse effects on growth and development, and results in increased risk for developmental delay, neurological abnormalities and neuropsychological deficits.[3]

Several studies have suggested that children with CKD have increased risk for a wide range of delays in motor and cognitive development, particularly for children with ESRD.[4]

Most studies have demonstrated lower intelligent quotient (IQ) scores among children with ESRD than in unaffected siblings or the general population, and also when comparing pre- and posttransplantation performances.[5]

Memory deficits also have been identified in children with mild CKD as well as ESRD.[6]

Most of these studies were done in Western countries, with only a few studies conducted in the developing world. The lack of research on psychological morbidity in developing countries has led to a gap in assessing the global burden of disease.[7]

Bakr et al found that adjustment disorders were the most common disorders (18.4%) among children with ESRD on regular hemodialysis (HD), followed by depression (10.3%) and neurocognitive disorders (7.7%). In Egypt, as in many developing countries, the focus of health-care is on medical problems of the adults and rarely they address the social and psychological needs of children and adolescents, especially those with a chronic illness like CKD.[8]

Therefore, the present study aimed to evaluate cognitive functions and adaptive behavior in children with ESRD.


   Aim Top


This study aimed to assess the cognitive functions and adaptive behavior in children with ESRD on regular HD.


   Subjects and Methods Top


Subjects

This case-controlled study was conducted on 30 children suffering from ESRD who were on treatment at the Pediatric Nephrology Unit of Tanta University Hospital. Thirty apparently healthy children served as a control group; the study was conducted during the period from January 2017 to January 2018.

Inclusion criteria

The inclusion criteria included children having ESRD receiving regular HD for at least six months.

Exclusion criteria

  • Children having ESRD on various modalities of renal replacement therapy such as peritoneal dialysis or renal transplantation.
  • Children having intellectual disabilities or any neurological disorders prior to the onset of ESRD.
  • Children suffering from any chronic illness other than CKD.


Ethical considerations

Informed verbal and/or written consents were obtained from the guardians of all cases and controls included in this study. The study was approved by the Ethical Committee of Tanta University.

Methods

All children were subjected to the following:

  1. Full history taking: It included age, past history of diseases and medications, dialysis duration, developmental history, the exact age and order of sequences of the body and psychological changes of pubertal development and, age at first appearance of axillary, and pubic hair.
  2. Detailed physical and neurological examination.
  3. Anthropometric measurements including:


    1. Weight measured using self-calculating scale that is recording to the nearest 0.1 kg
    2. Height: measured against an appropriate vertical measure that is recording to the nearest 0.1 cm
    3. Body mass index: calculated as weight in kg\Height in m2; patients were grouped as normal <85th percentile, over weight >85th percentile or obese >95th percentile.[9]


  4. Routine laboratory investigations:


    1. Complete blood picture[10]
    2. Kidney function tests[11]
    3. Liver function tests[11]
    4. Serum Calcium[12]
    5. Serum phosphorus[12]
    6. Serum ferritin[13]
    7. Parathyroid hormone.[12]


  5. Specific investigations:


  1. Assessment of intelligence (IQ): using Stanford Binet test 5th edition[14]
  2. Assessment of adaptive behavior: by adaptive behavior scale 2nd edition using Arabic form translated by Dr. Fadya Alwan.


  3. Adaptive behavior has been an integral, although sometimes unstated, part of the long history of mental retardation and its definition. In the 19th century, mental retardation was recognized principally in terms of a number of factors that included awareness and understanding of surroundings, ability to engage in regular economic and social life, dependence on others, the ability to maintain one’s basic health and safety, and individual respon- sibility.[15]
  4. Assessment of executive functions by using:


  1. Wisconsin Card Sorting Test (WCST)


  2. The WCST, originally developed to assess abstract reasoning ability and the ability to shift cognitive strategies in response to changing environmental contingencies, is also considered a measure of the executive functions. Similar to other measures of the executive functions, the WCST also requires strategic planning, organized searching, utilizing environmental feedback to shift cognitive sets, directing behavior towards achieving a goal and modulating impulsive responding.[16] In the computerized version of WCST, the patients were directed to choose one of four target cards that matched a test card in shape, color, or the number of stimuli. Computer feedback indicated whether the responses were correct. Once 10 consecutive correct matches were made, the sorting criteria changed without warning and subjects were required to use a different sorting strategy.[17]

  3. Continuous Performance Test (CPT)


The very complexity of the atten- tional and inhibition systems makes the question of how to adequately and accurately assess the integrity of the components of these systems formidable. CPTs represent one group of paradigms for the evaluation of attention and, to a lesser degree, impulsivity.[18] CPTs are computerized tests of attention. Generally, a series of varying shapes, pictures or letters flash on the screen and the test subject has to click a mouse button whenever the correct figure appears. The tests typically measure errors of omission which correlate with inattention and errors of commission which correlate with impulsivity. Time needed to click and variability of response time is also measured.[19]


   Statistical Analysis Top


The data were coded, entered, and processed on computer using the Statistical Package for the Social Sciences (SPSS) software version 18.0 (SPSS Inc., Chicago, IL, USA).[20] The results were represented in tabular and diagrammatic forms and then interpreted. Mean, standard deviation, range, frequency, and percentage were used as descriptive statistics. The following tests were performed:

  1. Chi-square test was used to test the association variables for categorical data.
  2. Chi-square test was used to test the association variables for categorical data.
  3. Student’s /-test was used to assess the statistical significance of the difference between two population means in a study involving independent samples.
  4. Spearman correlation was used in the correlation between two parametric parameters.


P <0.05 was considered statistically significant.


   Results Top


[Table 1] summarizes IQ in patients and controls. There was a statistically significant decrease among patients than controls.
Table 1: Intelligence quotient in patients and controls.

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[Table 2] summarizes adaptive behavior scale (Vineland Test) in patients and controls. There was a statistically significant decrease in the Vineland test among patients than controls.
Table 2: Adaptive behavior scale (Vineland Test) in patients and controls.

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[Table 3] summarizes the WCST in patients and controls (perseverative errors). The test was impaired in patients in comparison to controls.
Table 3: Wisconsin Card Sorting Test in patients and controls (perseverative errors).

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[Table 4] summarizes the CPT (commission errors) in patients and controls. There was statistically significant increase in commission errors among patients than controls.
Table 4: Continuous Performance Test (commission errors) in patients and controls.

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[Table 5] summarizes correlation between IQ and other variables. There was no statistically significant correlation between IQ and age, hemoglobin (Hb), platelet count (PLT), total leukocyte count (TLC), blood urea, creatinine (Cr), alanine aminotransferase (ALT), aspartate aminotransferase (AST), serum bilirubin), phosphorus (PH), calcium (Ca), ferritin, WCST, CPT, weight, height, blood pressure (BP), pulse pressure, and duration on dialysis. There was statistically significant positive correlation between IQ and Vineland [Figure 1].
Figure 1: Correlation between intelligence quotient and Vineland.

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Table 5: Correlation between intelligence quotient and other variables.

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[Table 6] summarizes the correlation between Vineland and other variables. There was no statistically significant correlation between Vineland and age, Hb, PLT, TLC, urea, Cr, ALT, DSB, total serum bilirubin (TSB), S. PH, serum Ca, serum ferritin, WCST, para- thormone, weight, height, systolic blood pressure (SBP), diastolic blood pressure (DBP) and pulse pressure). There was a statistically significant positive correlation between Vineland and AST, CPT [Figure 2] and [Figure 3], respectively).
Figure 2: Correlation between Vineland and AST.

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Figure 3: Correlation between Vineland and continuous performance test.

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Table 6: Correlation between Vineland and other variables.

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[Table 7] summarizes the correlation between WCST and other variables. There was no statistically significant correlation between WCST and age, Hb, PLT, TLC, urea, Cr, ALT, DSB, TSB, S. PH, serum calcium, serum ferritin, WCST, parathormone, weight, height, SBP, DBP, and pulse pressure). There was a statistically significant positive correlation between WCST and AST, CPT [Figure 4] and [Figure 5], respectively).
Figure 4: Correlation between Wisconsin Card Sorting Test and AST.

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Figure 5: Correlation between Wisconsin Card Sorting Test and Continuous Performance Test.

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Table 7: Correlation between Wisconsin Card Sorting Test and other variables.

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[Table 8] summarizes the correlation between CPT and other variables. There was no statistically significant correlation between CPT and age, Hb, PLT, TLC, Urea, Cr, ALT, DSB, TSB, S.PH, serum calcium, serum ferritin, WCST, parathormone, weight, height, SBP, DBP, and pulse pressure). There was a statistically significant positive correlation between CPT and AST [Figure 6].
Figure 6: Correlation between continuous performance test and AST.

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Table 8: Correlation between continuous performance test and other variables.

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   Discussion Top


CKD is increasingly a public health problem. It is characterized by progressive destruction of renal mass with irreversible sclerosis and loss of nephrons over a period of at least months to many years, depending on the underlying etiology. Cognitive impairment is common in end-stage renal disease (ESRD) patients in comparison with the general population.[21]

Previous studies have shown that children and adult survivors of childhood-onset end stage kidney disease have a greater frequency of neurodevelopmental and cognitive challenges compared with the general population.[22],[23] This study showed that, mean value of IQ was significantly lower among patients than controls. This agrees with Amr et al,[24] who found that the mean value of IQ was significantly lower among their patients than their controls.

This supports previous studies that have documented lower IQ scores among children with CKD compared with healthy children.[3]

It has been found that children with renal disease in all stages of therapy (predialysis, dialysis, and transplant) performed worse than controls on a series of neuropsychological tests and this difference became more marked over time.[6]

This effect does not appear to fluctuate directly with the changes in serum urea nitrogen, as study of children before and after HD sessions did not demonstrate improvement in performance on measures of attention, problem solving, and paired associate learning after HD.[25]

This agrees also with Haavisto et al,[26] who identified lower IQ in children with kidney disease compared with healthy age-matched controls.

Furthermore, Kerry et al,[27] reported that children with CKD also had lower scores than the general population in executive functions and memory domains, and they scored lower in tests of academic skills related to mathematics, reading, and spelling.

This study showed that, mean value of adaptive behavior scale (Vineland test) was significantly lower among patients than controls.

The Vineland test is a standardized measure of adaptive behavior, the things that people do to function in their everyday lives. Whereas ability measures focus on what the examinee can do in a testing situation, the Vineland focuses on what he or she actually does in daily life. Because it is a norm-based instrument, the examinee’s adaptive functioning is compared to that of others his or her age.[28]

This agrees with Kaufman et al,[29] and Kaufman et al,[28] who found that mean values of Vineland were significantly lower among their patients than their controls.

The WCST is one of the most widely used neurocognitive test for assessing executive function that has been strongly linked to prefrontal cortical function, reflecting an integrated ability for the purpose of planning and executing goal-directed activities.[30]

This study showed that, mean value of WCST (perseverative errors) was statistically decreased in patients in comparison to controls.

This agrees with Lin et al,[30] who found that, mean value of WCST was decreased in their patients in comparison to controls.

The very complexity of the attentional and inhibition systems makes the question of how to adequately and accurately assess the integrity of the components of these systems formidable. CPT represents one group of paradigms for the evaluation of attention and, to a lesser degree, impulsivity. The tests typically measure errors of omission which correlate with inattention and errors of commission which correlate with impulsivity. Time needed to click and variability of response time is also measured.[31]

In the current study, mean value of continuous performance test (commission errors) was significantly impaired among patients than controls.

This was in agreement with Hartung et al,[32] who found that the mean value of CPT (commission errors) was significantly impaired among patients than controls.

Owolabi et al,[33] aimed to evaluate cognitive function in ESRD patients in comparison with age, sex, and level of education-matched controls in a cross-sectional study involving 80 ESRD patients receiving maintenance HD treatment and recruited conservatively at the nephrology unit of Aminu Kano Teaching Hospital during the study period from June 2010 to June 2014. Eighty apparently healthy age, sex, and education matched controls, were also recruited. They found that a significant difference existed across all the cognitive domains assessed in ESRD patients in comparison with controls. This finding is in conformity with reports from other workers e.g. Groothoff et al,[22] Bawden et al,[3] and Etgen.[31]

Cognitive dysfunction may occur as a result of deficits in a number of domains of cognition including concentration, judgment, abstraction, memory, and executive functions and this may impair the patients’ capability. There is a growing body of evidence in adults and to some extent in adolescents and pediatrics that CKD is associated with comorbi- dities such as hypertension, diabetes mellitus, hyperlipidemia, and cardiovascular stroke that are known to increase the risk of cognitive impairment.[34],[35]

The mechanism underlying cognitive impairment in persons with ESRD is largely unknown. The mechanisms proposed as mediators of relations between kidney function and cognition are similar to those that have been advanced to explain relations between other risk factors for cardiovascular disease and cognition.[36]

Earlier studies have demonstrated that renal transplantation is associated with improvements in both neuropsychological tests such as the mini-mental state examination, and neuro- physiological markers of cognitive function measured using evoked potential latencies and electroencephalographic rhythms.[37]

This cognitive impairment does not only have implication for the patient’ s ability to participate in adequate care of the ESRD but also have major implications for informed consent in relation to dialysis initiation or maintenance, and ultimately, renal transplan-tation.[38],[39]

Cognitive dysfunctions in CKD patients have implication for therapy and quality of life. For instance, cognitive impairment in ESRD patients that is severe enough to preclude reliable compliance is an established contraindication to kidney transplantation.[40]

The limitations of this study were the small number of patients who accepted to participate in this work and the difficulty in performing intelligence test and tests of executive functions in some patients due to poor cooperation.


   Conclusion Top


From this study it can be concluded that.

  1. Children with ESRD had lower IQ and adaptive behavior than healthy control children.
  2. Executive functions were lower in children with ESRD than healthy control children.



   Recommendations Top


From this study it can be recommended that:

  1. A future study should be done on a larger number of children and adolescents with ESRD to evaluate cognition and behaviour of these patients.
  2. It is important to asses the cognitive and executive functions in children with ESRD to give them the chance of good rehabilitation and better quality of life.


Conflict of interest: None declared.



 
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Kohli A, Kaur M. Wisconsin card sorting test: Normative data and experience. Indian J Psychiatry 2006; 48:181-4  Back to cited text no. 16
    
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Correspondence Address:
Mohamed Abdelaziz El-Gamasy
Department of Pediatrics, Faculty of Medicine, Tanta University, Tanta, Gharbia Governate
Egypt
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DOI: 10.4103/1319-2442.284014

PMID: 32394912

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    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6]
 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6], [Table 7], [Table 8]



 

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    Abstract
   Introduction
   Aim
   Subjects and Methods
   Statistical Analysis
   Results
   Discussion
   Conclusion
   Recommendations
    References
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