Self-concept and academic achievement in children with chronic kidney disease.

BACKGROUND: Within the pediatric population, a positive self-concept is associated with better academic achievement. Children with chronic kidney disease (CKD) are at risk for lower quality of life and academic underachievement. Little is known about self-concept among children with CKD and how self-concept influences academic achievement. The objectives of the present study were to (1) describe patient-reported self-concept among children with CKD and (2) evaluate the relationship between self-concept and academic performance. METHODS: This cross-sectional study included 23 children, aged 6-16 years, with mild to moderate CKD (cause of disease due to congenital anomalies of the kidney and urinary tract) and 26 age-matched comparators. Participants completed the Self-Description Questionnaire (SDQ) and the Wide Range Achievement Test (WRAT-4). Linear regression models were used to evaluate self-concept as a predictor of academic achievement in the CKD cohort. RESULTS: Self-concept ratings were comparable between children with CKD and non-CKD comparators; however, academic achievement trended lower for the CKD patients on measures of arithmetic (estimate = - 0.278, 95% confidence interval (CI) [- 0.530: - 0.026], t(45) = - 1.99, p = 0.053). All of the SDQ domains predicted WRAT-4 arithmetic performance, such that higher scores on the SDQ were associated with higher scores in mathematics. Kidney function did not have an effect on the relationship between self-concept and academic achievement. CONCLUSIONS: Despite the presence of a chronic disease, children with CKD endorse a positive self-concept. Positive self-concept may predict academic success in this population.

Does kidney transplant improve health-related quality of life for youth with chronic kidney disease?

Youth with chronic kidney disease are known to have impaired health-related quality of life (HRQOL), particularly as the disorder increases in severity. Few prospective, longitudinal investigations of HRQOL within the context of pediatric chronic kidney disease exist. In the current issue, Guha et al. provide a longitudinal assessment of HRQOL for a cohort of youth with chronic kidney disease. Their findings suggest that children may experience meaningful improvement in HRQOL when they transition from dialysis to transplant.

Improving Clinical Care for Children With CKD: A Report From a National Kidney Foundation Scientific Workshop.

Development of clinical guidelines and recommendations to address the care of pediatric patients with chronic kidney disease (CKD) has rarely included the perspectives of providers from a variety of health care disciplines or the patients and parents themselves. Accordingly, the National Kidney Foundation hosted an in-person, one and a half-day workshop that convened a multidisciplinary group of physicians, allied health care professionals, and pediatric patients with CKD and their parents, with the goal of developing key clinical recommendations regarding best practices for the clinical management of pediatric patients living with CKD. The key clinical recommendations pertained to 5 broad topics: addressing the needs of patients and parents/caregivers; modifying the progression of CKD; clinical management of CKD-mineral and bone disorder and growth retardation; clinical management of anemia, cardiovascular disease, and hypertension; and transition and transfer of pediatric patients to adult nephrology care. This report describes the recommendations generated by the participants who attended the workshop.

A longitudinal analysis of the effect of anemia on executive functions in children with mild to moderate chronic kidney disease.

BACKGROUND: Children with chronic kidney disease (CKD) are at risk for cognitive dysfunction. The aim of this study was to investigate associations between executive functions (EF), anemia, and iron deficiency. METHODS: A total of 688 children > 6 years of age enrolled in the Chronic Kidney Disease in Children (CKiD) study who underwent evaluation for EF were included. Hemoglobin (Hgb) was characterized as low (1st-5th percentile) or very low (< 1st percentile) compared to normative values for age, sex, and race irrespective of erythropoiesis-stimulating agent (ESA) usage. Longitudinal analysis was conducted using consecutive visit pairs, with anemia status defined as new onset, resolved, or persistent. Linear mixed models with random intercept were used and adjusted for key covariates. RESULTS: Anemia was present in 41% of children, and median Hgb was 11.8 gm/dl. New onset anemia was associated with lower digit span total score (- 0.75, 95% CI - 1.36, - 0.15, p = 0.01). Persistent anemia was associated with lower scores on color-word inhibition/switching (ß = - 0.98; 95% CI - 1.78, - 0.18, p = 0.02). Errors of omission were significantly higher (worse) in those with persistent anemia (ß = 2.67, 95% CI 0.18, 5.17, p = 0.04). Very low Hgb levels were significantly associated with lower color-word inhibition/switching scores (ß = - 1.33, 95% CI - 2.16, - 0.51; p = 0.002). Anemia and low GFR were associated with lower category fluency scores compared to non-anemic subjects with higher GFR (ß = - 1.09, 95% CI - 2.09, - 0.10, p = 0.03). CONCLUSIONS: The presence of anemia, in addition to its severity and duration in children with CKD, is associated with poorer scores on select measures of EF. A higher resolution version of the Graphical abstract is available as Supplementary information.

Longitudinal changes of health-related quality of life in childhood chronic kidney disease.

BACKGROUND: Few longitudinal studies have evaluated the impact of chronic kidney disease (CKD) duration on health-related quality of life (HRQOL). The study's aim was to determine how HRQOL changes over time in childhood CKD. METHODS: Study participants were children in the chronic kidney disease in children (CKiD) cohort who completed the pediatric quality of life inventory (PedsQL) on three or more occasions over the course of two or more years. Generalized gamma (GG) mixed-effects models were applied to assess the effect of CKD duration on HRQOL while controlling for selected covariates. RESULTS: A total of 692 children (median age = 11.2) with a median of 8.3 years duration of CKD were evaluated. All subjects had a GFR greater than 15 ml/min/1.73 m2. GG models with child self-report PedsQL data indicated that longer CKD duration was associated with improved total HRQOL and the 4 domains of HRQOL. GG models with parent-proxy PedsQL data indicated that longer duration was associated with better emotional but worse school HRQOL. Increasing trajectories of child self-report HRQOL were observed in the majority of subjects, while parents less frequently reported increasing trajectories of HRQOL. There was no significant relationship between total HRQOL and time-varying GFR. CONCLUSIONS: Longer duration of the disease is associated with improved HRQOL on child self-report scales; however, parent-proxy results were less likely to demonstrate any significant change over time. This divergence could be due to greater optimism and accommodation of CKD in children. Clinicians can use these data to better understand the needs of pediatric CKD patients. A higher resolution version of the Graphical abstract is available as Supplementary information.

Overview of the findings and advances in the neurocognitive and psychosocial functioning of mild to moderate pediatric CKD: perspectives from the Chronic Kidney Disease in Children (CKiD) cohort study.

The Chronic Kidney Disease in Children (CKiD) prospective cohort study was designed to address the neurocognitive, growth, cardiovascular, and disease progression of children and adolescents with mild to moderate CKD. The study has had continuous funding from NIDDK for 17 years and has contributed significant advances in pediatric CKD. The goals of this educational review are threefold: (1) to provide an overview of the neurocognitive and psychosocial studies from CKiD to date; (2) to provide best practice recommendations for those working with the neurocognitive and psychosocial aspects of pediatric CKD based on CKiD findings; and (3) to help chart future goals and directives for both research and clinical practice. This collection of 22 empirical studies has produced a number of key findings for children and adolescents with mild to moderate CKD. While various studies suggest a relatively positive presentation for this population as a whole, without evidence of significant impairment or deterioration, findings do indicate the presence of neurocognitive dysfunction, emotional-behavioral difficulties, and lower quality of life for many children with CKD. These findings support the promotion of best practices that are accompanied by additional future clinical and research initiatives with this patient population.

Patient- and parent proxy-reported outcome measures for life participation in children with chronic kidney disease: a systematic review.

BACKGROUND: The burden of chronic kidney disease (CKD) and its treatment may severely limit the ability of children with CKD to do daily tasks and participate in family, school, sporting and recreational activities. Life participation is critically important to affected children and their families; however, the appropriateness and validity of available measures used to assess this outcome are uncertain. The aim of this study was to identify the characteristics, content and psychometric properties of existing measures for life participation used in children with CKD. METHODS: We searched MEDLINE, Embase, PsychINFO, Cumulative Index to Nursing and Allied Health Literature and the Cochrane Kidney and Transplant register to August 2019 for all studies that used a measure to report life participation in children with CKD. For each measure, we extracted and analyzed the characteristics, dimensions of life participation and psychometric properties. RESULTS: From 128 studies, we identified 63 different measures used to assess life participation in children with CKD. Twenty-five (40%) of the measures were patient reported, 7 (11%) were parent proxy reported and 31 (49%) had both self and parent proxy reports available. Twenty-two were used in one study only. The Pediatric Quality of Life Inventory version 4.0 generic module was used most frequently in 62 (48%) studies. Seven (11%) were designed to assess ability to participate in life, with 56 (89%) designed to assess other constructs (e.g. quality of life) with a subscale or selected questions on life participation. Across all measures, the three most frequent activities specified were social activities with friends and/or family, leisure activities and self-care activities. Validation data in the pediatric CKD population were available for only 19 (30%) measures. CONCLUSIONS: Life participation is inconsistently measured in children with CKD and the measures used vary in their characteristics, content and validity. Validation data supporting these measures in this population are often incomplete and are sparse. A meaningful and validated measure for life participation in children with CKD is needed.

Bicarbonate, blood pressure, and executive function in pediatric CKD-is there a link?

BACKGROUND: In adult chronic kidney disease (CKD), metabolic acidosis is associated with diminished cognition, notably executive function (EF). Data from the Chronic Kidney Disease in Children (CKiD) study demonstrate a risk for impairment of EF, a finding associated with heightened blood pressure variability (BPV). We sought to determine whether low serum bicarbonate is also associated with performance on tests of EF in pediatric CKD and to investigate potential interaction with BPV. METHODS: CKiD participants with serum bicarbonate, blood pressure, and selected cognitive measurements available were evaluated. An EF summary score was derived from scores on the Delis-Kaplan Executive Function System, Conners' Continuous Performance Test, and Digit Span Backwards subtest from the Wechsler Intelligence Scale for Children-IV-Integrated. Parents completed the Behavioral Rating Inventory of Executive Function (BRIEF) to yield a Global Executive Composite (GEC) score. Linear mixed models with bicarbonate and hypertension as predictors and linear regression with bicarbonate and BPV were used to predict EF level. RESULTS: Data were available for 865 children. Twenty-two percent had low bicarbonate (CO2 ≤ 20 mmol/L) at baseline. On multivariate analysis, there was no relationship between bicarbonate, hypertension, and EF. There was no significant CO2×hypertension interaction found. A significant interaction (p = 0.01) between high CO2 (≥ 26 mmol/L) and BPV was detected in the model with GEC as the EF outcome, indicating that while higher BPV was associated with worse EF in the low and normal CO2 groups, higher BPV was associated with better EF in the high CO2 group. CONCLUSIONS: Our analyses revealed an interaction between one measure of BPV and low bicarbonate on neurocognition in pediatric CKD, suggesting a potential role for control of both bicarbonate and blood pressure in preserving cognition in early CKD. Further research is needed to confirm and further define this association.

A longitudinal analysis of the effect of anemia on health-related quality of life in children with mild-to-moderate chronic kidney disease.

BACKGROUND: To evaluate impact of anemia on health-related quality of life (HRQOL) over time in a large pediatric cohort with mild-to-moderate chronic kidney disease (CKD). METHODS: Participants were enrolled in the Chronic Kidney Disease in Children Study (CKiD), a multicenter, longitudinal cohort. HRQOL was measured using the Pediatric Quality of Life Inventory (PedsQL). Anemia was defined as hemoglobin < 5th percentile for age, sex, and race. Two longitudinal analyses were conducted on consecutive visit pairs. Models examined effects of anemia status on both HRQOL score over time and change in HRQOL score between consecutive visits. The sample included 733 children with a median estimated GFR 54 ml/min/1.73 m2. Thirty percent of children had anemia at index visit. RESULTS: Analysis of HRQOL scores revealed the presence of anemia was associated with significantly lower overall HRQOL (ß = - 2.90 (95% CI = - 7.74, - 0.21), p = 0.04) and physical functioning (ß = - 5.72 (- 9.49, - 2.25), p = 0.001) according to children. On parent ratings, the development of anemia was associated with lower emotional functioning scores (ß = - 4.87 (- 8.72, - 0.11), p = 0.045). In the second model, children who developed anemia were rated by caregivers as having more decreased physical functioning than children who remained anemia-free (ß = - 3.30 per year (- 5.83, - 0.76), p = 0.01). Caregivers did not observe declines in their children's other PedsQL subscales in the presence of developed anemia. Children with resolved or persistence did not show improvement or decline in any aspect of HRQOL functioning relative to non-anemic subjects. CONCLUSIONS: In children with CKD, anemia has an adverse effect on HRQOL which persists over time but does not appear to be progressive.

A longitudinal examination of parent-reported emotional-behavioral functioning of children with mild to moderate chronic kidney disease.

BACKGROUND: Children with mild to moderate chronic kidney disease (CKD) are at increased risk for deficits in neurocognition. Less is known about how CKD affects emotional-behavioral functioning in this population. METHODS: Parent ratings of emotional-behavioral functioning at baseline and over time were examined for 845 children with mild to moderate CKD using the Behavior Assessment System for Children, Second Edition Parent Rating Scales (BASC-2 PRS). Associations with demographic and disease-related predictors were also examined. RESULTS: Children with mild to moderate CKD had parent-reported emotional-behavioral functioning largely within normal limits, at baseline and over time. The proportion with T-scores at least 1 SD above the mean was 24% for Internalizing Problems and 28% for Attention Problems. A greater proportion of participants scored lower than expected (worse) on scales measuring adaptive skills (25%). Persistent hypertension predicted attention problems (ß = 1.59, 95% CI = 0.24 to 2.94, p < 0.02) and suggested worse behavioral symptoms (ß = 1.36, 95% CI = - 0.01 to 2.73, p = 0.05). Participants with proteinuria at baseline, but not at follow-up, had fewer attention problems than participants whose proteinuria had not resolved (ß = - 3.48, CI = - 6.79 to - 0.17, p < 0.04). Glomerular diagnosis was related to fewer (ß = - 2.68, 95% CI = - 4.93 to - 0.42, p < 0.02) internalizing problems. CONCLUSIONS: Although children with CKD generally have average emotional-behavioral parent ratings, a notable percentage of the population may be at risk for problems with attention and adaptive behavior. Providers working with this population should facilitate psychosocial referrals when indicated.

Academic achievement in children with chronic kidney disease: a report from the CKiD cohort.

BACKGROUND: There are limited data to describe academic achievement outcomes for children with mild to moderate pediatric chronic kidney disease (CKD). The objective of this study was to describe the prevalence of low academic achievement in patients with mild to moderate CKD. METHODS: Wechsler Individual Achievement Test, Second Edition, Abbreviated (WIAT-II-A) data were collected at entry into the Chronic Kidney Disease in Children (CKiD) study. Achievement in basic reading, spelling, mathematics, and total achievement was evaluated with a focus on the effects of comorbid CKD-related variables, neurocognitive, and school-based characteristics on academic achievement. RESULTS: WIAT-II-A data were available for 319 children in the CKiD cohort. Low total academic achievement was present in 34% percent of the sample. There was no significant effect of CKD-related medical variables on academic achievement. Mathematics had the lowest distribution of achievement scores. In univariate models, low achievement was significantly related to days of missed school (p = 0.006) and presence of individualized education plan (p < 0.0001). CONCLUSIONS: Low academic achievement was seen in over one-third of children with CKD, with the most difficulty observed in the domain of mathematics. Providers and educators should monitor for academic difficulties in this population in order to facilitate early educational assistance and promote positive educational outcomes.

No guts, no glory: models of integrated care within a GI subspecialty practice.

The focus in pediatric medicine has shifted from a concentration on mortality and morbidity to a more comprehensive view encompassing the physical, social, and psychological aspects of health. What follows is a description of four integrated, collaborative care clinics within the GI subspecialty at Children's Mercy Kansas City that specifically address this trend in pediatric healthcare. With these descriptions, we hope to inform broader acceptance and utilization of similar models across other pediatric populations.

Long-term neurocognitive outcomes of patients with end-stage renal disease during infancy.

BACKGROUND: End-stage renal disease (ESRD) during infancy has been associated with poor short-term neurocognitive outcomes. Limited information exists regarding long-term outcomes. METHODS: Neurocognitive outcomes for 12 patients diagnosed with ESRD during the first 16 months of life were assessed. Nine patients (mean age: 11 years) were compared to their healthy siblings (mean age: 10 years) on measures of intellectual and executive functioning, memory, and academic achievement using paired-samples t tests. RESULTS: Patients' Full Scale IQ (FSIQ) scores (M = 78, SD = 16.1) were significantly lower than sibling controls (M = 94, SD = 18.9; p < 0.03). For patients, FSIQ negatively correlated with total months on dialysis (r = -0.6, p < 0.04), as did WISC-IV Processing Speed (r = -0.6, p < 0.05). Patients' scores on the Metacognition Index of the BRIEF (M = 61.4, SD = 16.3) were significantly higher (indicating greater risk for dysfunction) than siblings (M = 46.7, SD = 6.4; p < 0.04). Patients' scores (M = 84, SD = 19) on the WIAT-II-A Total Achievement were significantly lower than siblings (M = 103, SD = 20, p < 0.01). Younger age at transplant was associated with higher scores on measures of Processing Speed (r = -0.7, p < 0.05), as well as higher scores on measures of executive functioning, memory, and academic achievement. CONCLUSIONS: In summary, patients diagnosed with ESRD as infants had intellectual and metacognitive functioning significantly lower than sibling controls. Fewer months on dialysis and younger age at transplant were associated with better outcomes.

Barramundi (Lates calcarifer) desaturase with Δ6/Δ8 dual activities.

Barramundi is a commercially farmed fish in Australia. To examine the potential for barramundi to metabolise dietary α-linolenic acid (ALA, 18:3 n-3), the existence of barramundi desaturase enzymes was examined. A putative fatty acid Δ6 desaturase was cloned from barramundi liver and expressed in yeast. Functional expression revealed Δ6 desaturase activity with both the 18 carbon (C(18)) and C(24) n-3 fatty acids, ALA and 24:5 n-3 as well as the C(18) n-6 fatty, linoleic acid (LA, 18:2 n-6). Metabolism of ALA was favoured over LA. The enzyme also had Δ8 desaturase activity which raises the potential for synthesis in barramundi of omega-3 (n-3) long chain polyunsaturated fatty acids from ALA via a pathway that bypasses the initial Δ6 desaturase step. Our findings not only provide molecular evidence for the fatty acid desaturation pathway in the barramundi but also highlight the importance of taking extracellular fatty acid levels into account when assessing enzyme activity expressed in Saccharomyces cerevisiae.

Neurocognition in Pediatric Chronic Kidney Disease: A Review of Data From the Chronic Kidney Disease in Children (CKiD) Study.

Pediatric chronic kidney disease (CKD) is associated with deficits in neurocognitive functioning, ranging from mild to severe, and correlated with the severity of kidney disease. Clinical variables that are associated with neurocognitive deficits include lower kidney function, hypertension, proteinuria, and metabolic acidosis. Commonly reported neurocognitive difficulties include academic underachievement and deficits in attention regulation and executive function as well as somewhat lower intellectual abilities compared with peer and normative data. Although often mild, these neurocognitive deficits may have broad implications for quality of life and likely contribute to both poorer high school graduation rates and long-term underemployment in the adult CKD population. The presence of neurocognitive deficits in predialytic CKD has been well characterized, but further longitudinal research is warranted to describe cognitive changes as children progress from early stage CKD to kidney replacement therapy. Such studies should include both cognitive and neuroimaging evaluations to better inform the impact of CKD progression on neurocognitive outcomes.

The Similarities and Differences Between Glomerular vs. Non-glomerular Diagnoses on Intelligence and Executive Functions in Pediatric Chronic Kidney Disease: A Brief Report.

Pediatric chronic kidney disease (CKD) appears to be a heterogeneous group of conditions, but this heterogeneity has not been explored with respect to its impact on neurocognitive functioning. This study investigated the neurocognitive functioning of those with glomerular (G) vs. non-glomerular (NG) diagnoses. Data from the North American CKiD Study were employed and the current study included 1,003 children and adolescents with mild to moderate CKD. The G Group included 260 participants (median age = 14.7 years) and the NG Group included 743 individuals (median age = 9.0 years). Neurocognitive measures assessed IQ, inhibitory control, attention regulation, problem solving, working memory, and overall executive functioning. Data from all visits were included in the linear mixed model analyses. After adjusting for sociodemographic and CKD-related covariates, results indicated no differences between the diagnostic groups on measures of IQ, problem solving, working memory, and attention regulation. There was a trend for the G group to receive better parent ratings on their overall executive functions (p < 0.07), with a small effect size being present. Additionally, there was a significant G group X hypertension interaction (p < 0.003) for inhibitory control, indicating that those with both a G diagnosis and hypertension performed more poorly than the NG group with hypertension. These findings suggest that the separation of G vs. NG CKD produced minimal, but specific group differences were observed. Ongoing examination of the heterogeneity of pediatric CKD on neurocognition, perhaps at a different time point in disease progression or using a different model, appears warranted.

Endothelial cell COX-2 expression and activity in hypoxia.

The clinical experience with selective cyclooxygenase (COX)-2 inhibitors reveals there are important protective roles for COX-2 in the cardiovascular system. This study examined the response to hypoxia of endothelial cell eicosanoid synthesis with respect to the role of COX-2 and its molecular regulation in hypoxia. Human umbilical vein endothelial cells (HUVEC) were exposed to hypoxia and the effects on COX-2, prostacyclin (PGI(2)) and thromboxane (TXA(2)) synthesis were examined. COX-2 promoter constructs were used to examine the role of Hypoxia Inducible Factors (HIFs) in COX-2 responses to hypoxia. Hypoxia caused an increase in PGI(2) synthesis, but not TXA(2) synthesis. PGI(2), but not TXA(2) synthesis, was absolutely dependent on upregulation of COX-2 by hypoxia. Mutations of transcription factor binding sites in the promoter showed a lack of involvement of NFkappaB in the response to hypoxia, but suggested involvement of HIFs. Transfection of HUVEC with HIF expression vectors increased activity of the promoter construct and increased native COX-2 expression in normoxia. EMSA showed HIF binding in nuclear extracts of hypoxic HUVEC to a region of the COX-2 promoter. The endothelial cell response to hypoxia involves increased production of the anti-thrombotic eicosanoid, PGI(2), which is dependent on COX-2 upregulation by a HIF-mediated process.