الفهرس 
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Abstract
This cross sectional study was conducted on 100 subjects aged 8-18 years, 75 patients with CKD (stages 2, 3, 4 and 5) and 25 healthy controls at pediatric nephrology department, Ain Shams University. CKD patients were divided into 3 groups according to their GFR; group (A) (pre-dialysis stages 2 and 3), group B (predialysis stages 4 and 5) and group C (children on regular hemodialysis).
We aimed to assess the neurocognitive functions in pediatric patients with chronic renal disease using Wechsler Intelligence Scale, Benton Visual Retention Test (BVRT), and Wisconsin Card Sorting Test (WCST). Psychosocial status was assessed using Children Depression Inventory (CDI), and Children’s manifest anxiety scale (CMAS). Also we aimed to detect any structural MRI brain abnormalities in these children and to identify clinical variables that may be associated with neurocognitive dysfunction such as hypertension, and anemia.
Our findings suggest that children with CKD have low-average intellectual functions (full-scale intelligence quotient) compared with the general population. Cognition seems to worsen with advancing CKD, with the poorest performance observed in children on dialysis. Both verbal and performance IQ were lower in CKD patients than their matched controls. However the deterioration in PIQ was more pronounced than that of the VIQ in all CKD groups. Moreover in the present study certain verbal IQ subsets were more affected than other subsets in children with mild to moderate CKD. These children had worse scores at “digit span” than at the remaining verbal IQ subsets; comprehensive, arithmetic ability, & similarity. With progression of the chronic kidney disease, the deterioration progressed to include the remaining subsets of the VIQ. Digit Span subtest is a measure of short-term verbal memory and attention. Also these children had worse scores in certain subsets of PIQ in comparison to the remaining subsets. The deterioration at “Coding “scores were more pronounced than that of other subsets of PIQ. With the progression of the chronic kidney disease, the deterioration progressed to include the remaining subsets of PIQ.
CKD patients had deficits observed at other cognitive functions including attention, memory (visual) and executive function denoted by worse scores at BVRT and WCST.
In the current study, VIQ was significantly higher in children with higher SES. Also IQ scores were influenced by school performance; children who did not DROP out of school, did not repeat grades IQ, and had lesser duration of school absence had significantly higher scores of TIQ, VIQ, & PIQ. Prolonged duration of CKD was associated with worse TIQ & VIP scores in our CKD patients. Moreover IQ scores were positively correlated with hemoglobin levels, but negatively correlated with serum levels of parathyroid hormone.
BVRT scores were affected by the duration of chronic kidney disease, school performance, GFR, and PTH levels. Children with CKD having a “disability” regarding BVRT scores “worse performance” had significantly longer duration of CKD, lower GFR, and higher PTH levels. As regards school performance, the percentage of CKD patients with worse Benton scores was higher in those who repeated school grades, dropped out school and did not attend school regularly.
WCST scores were influenced by SES, school performance, age of onset and duration of CKD, and PTH levels. The number of completed categories in WCST (better performance) was higher in children having higher socioeconomic status. Also it was positively correlated with the age of onset of CKD. However it was negatively correlated with the duration of CKD. As regards school performance; CKD patients who dropped out school, repeated grades, and had longer duration of school absence had a significantly higher number of trials administrated, and a lower number of completed categories at WCST and thus worse performance. Lastly higher PTH was associated with worse performance (higher number of trials administrated, and lower number of completed categories) at WCST. However neither blood pressure nor hemoglobin level was significantly associated with worse scores at BVRT or WCST.
Regarding psychosocial assessment, in the present study, 29% of children with CKD had depression either moderate or severe, while the corresponding figure for the control group was 8% using Children Depression Inventory (CDI). Twenty-six percent of children with CKD had moderate depression, & 2.6 % had severe depression. As regards anxiety we demonstrated that anxiety was more prevalent than depression. Moderate to severe anxiety was more prevalent in CKD patients 37% than the control group 12 % using Children’s Manifest Anxiety scale. However there was no statistical significance difference between CKD groups (P=0.064).Thirty percent of children with CKD had moderate anxiety and 6.6 % had severe anxiety.
We observed that depression among our CKD patients was associated with school performance, weight, and height. Children with CKD who did not attend school regularly or dropped out school had more depression rates. Also the stress of being stunted and underweight in comparison to their healthy peers was associated with depression. Moreover additional stressors such as the stigma of HCV infection and complications associated with the vascular access of dialysis may have a contributing role. Ten percent of all our CKD patients had HCV infection (8% on regular dialysis, and 2% with advanced CKD). Sixty-four percent of children on regular dialysis had aneurysmal dilatation of AV fistula, 44% had thrombosis, and 24% had infection requiring hospitalization. Furthermore the use of medications whose side effects include depression and anxiety may be one of the factors influencing rates of psychiatric disorders in the present study. About 56% (of children in group A were using these medications. However fewer number of patients in groups B & C were using these drugs 24 % &12 % respectively.
However in the current study depression was not associated with socioeconomic status, age of diagnosis, duration of CKD, presence of bone deformities, and hemoglobin level. Also there was no significant correlation between anxiety and the following factors: socioeconomic status, age of diagnosis and duration of CKD, school dropout, school grade repetition, school absence, weight, height, blood pressure, bone deformities, and glomerular filtration rate in our children with chronic kidney. However school absence was significantly the highest in patients with severe anxiety in the dialysis group.
Regarding MRI brain, the current study showed that white matter lesions were reported in two patients with CKD on regular dialysis and none of them had any neurological symptoms and signs. These white lesions were mainly periventricular, frontal, and subcortical. However there were neither silent infarcts nor microbleeds in any case in the current study.
As regards brain volumetry, there was no cases of global cerebral atrophy among our studied groups. However one case with CKD stage 3 was reported to have temporal lobe atrophy. Regarding specific areas of interest related to memory and attention such as hippocampus, caudate, putamen, globus pallidus, amygdala, and nucleus accumbens, the present study showed that there was no difference between CKD groups and control group apart from left caudate which surprisingly was larger in size in the dialysis group than in the control group. Regarding the function of the caudate nucleus it is a part of the basal ganglion that mediates procedural memory.
In the current study the hippocampal volume was negatively correlated with the duration of the CKD and serum PTH as well. The longer the duration of CKD, the smaller hippocampal volume. Similarly, the higher PTH, the smaller hippocampal volume. Regarding cerebral blood flow to hippocampus there was no statistically significant difference between groups B & C. However hippocampal perfusion on both sides was positively correlated with the GFR. Also left hippocampal perfusion was negatively correlated with the PTH.
In conclusion children with CKD may have poor neurocognitive functions and reduced educational attainment compared with healthy children and this was more evident with the progression of the kidney disease. Children with CKD may have average to low-average cognition compared with the general population, with significant deficits at educational outcomes, visual and verbal memory, attention, & executive function. Neuropsychiatric conditions including depression and anxiety disorders are also more prevalent among these patients especially in those on regular hemodialysis. All of these comorbidities may be contributing to poor quality of life in children with CKD.