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.

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.

Depressive Symptoms in Children with Chronic Kidney Disease.

OBJECTIVE: To assess depression in children with chronic kidney disease and to determine associations with patient characteristics, intellectual and educational levels, and health-related quality of life (HRQoL). STUDY DESIGN: Subjects aged 6-17 years from the Chronic Kidney Disease in Children cohort study completed the Children's Depression Inventory (CDI), Wechsler Abbreviated Scales of Intelligence, Wechsler Individual Achievement Test-II-Abbreviated, and the Pediatric Inventory of Quality of Life Core Scales 4.0. Regression analyses determined associations of CDI score and depression status with subject characteristics, intellectual and educational levels, and HRQoL. A joint linear mixed model and Weibull model were used to determine the effects of CDI score on longitudinal changes in glomerular filtration rate and time to renal replacement therapy. RESULTS: A total of 344 subjects completed the CDI. Eighteen (5%) had elevated depressive symptoms, and another 7 (2%) were being treated for depression. In adjusted analyses, maternal education beyond high school was associated with 5% lower CDI scores (estimate, 0.95; 95% CI, 0.92-0.99). Depression status was associated with lower IQ (99 vs 88; P = .053), lower achievement (95 vs 77.5; P < .05), and lower HRQoL by parent and child reports (effect estimates, -15.48; 95% CI, -28.71 to -2.24 and -18.39; 95% CI, -27.81 to -8.96, respectively). CDI score was not related to change in glomerular filtration rate. CONCLUSION: Children with depression had lower psychoeducational skills and worse HRQoL. Identifying and treating depression should be evaluated as a means of improving the academic performance and HRQoL of children with chronic kidney disease.

Association of blood pressure variability and neurocognition in children with chronic kidney disease.

BACKGROUND: Children with chronic kidney disease (CKD) and hypertension have increased blood pressure variability (BPV), which has been associated with lower neurocognitive test scores in adults. Children with CKD are at risk for decreased neurocognitive function. Our objective was to determine whether children with CKD and increased BPV had worse performance on neurocognitive testing compared with children with CKD and lower BPV. METHODS: This was a cross-sectional and longitudinal analysis of the relation between BPV and neurocognitive test performance in children ≥6 years enrolled in the Chronic Kidney Disease in Children (CKiD) study. Visit-to-visit BPV was assessed by the standard deviation of visit BPs (BPV-SD) and average real variability (ARV). Ambulatory BPV was assessed by SD of wake and sleep periods on 24-h ambulatory BP monitoring. RESULTS: We assessed 650 children with a mean follow-up period of 4.0 years. Children with systolic visit-to-visit BPV in the upper tertile had lower scores on Delis-Kaplan Executive Function System (D-KEFS) Verbal Category Switching than those with BPV in the lower tertile (BPV-SD, 8.3 vs. 9.5, p = 0.006; ARV, 8.5 vs. 9.6, p = 0.02). On multivariate analysis, the association between lower Category Switching score and increased BPV remained significant after controlling for mean BP, demographic characteristics, and disease-related variables [BPV-SD, ß = -0.7, 95 % confidence interval (CI) -1.28 to -0.12; ARV, ß = -0.54, CI -1.05 to -0.02). Ambulatory BPV was not independently associated with any cognitive measure. CONCLUSIONS: Higher systolic visit-to-visit BPV was independently associated with decreased D-KEFS Category Switching scores in children with mild-to-moderate CKD.

Duration of chronic kidney disease reduces attention and executive function in pediatric patients.

Chronic kidney disease (CKD) in childhood is associated with neurocognitive deficits. Affected children show worse performance on tests of intelligence than their unaffected siblings and skew toward the lower end of the normal range. Here we further assessed this association in 340 pediatric patients (ages 6-21) with mild-moderate CKD in the Chronic Kidney Disease in Childhood cohort from 48 pediatric centers in North America. Participants underwent a battery of age-appropriate tests including Conners' Continuous Performance Test-II (CPT-II), Delis-Kaplan Executive Function System Tower task, and the Digit Span Backward task from the age-appropriate Wechsler Intelligence Scale. Test performance was compared across the range of estimated glomerular filtration rate and duration of CKD with relevant covariates including maternal education, household income, IQ, blood pressure, and preterm birth. Among the 340 patients, 35% had poor performance (below the mean by 1.5 or more standard deviations) on at least one test of executive function. By univariate nonparametric comparison and multiple logistic regression, longer duration of CKD was associated with increased odds ratio for poor performance on the CPT-II Errors of Commission, a test of attention regulation and inhibitory control. Thus, in a population with mild-to-moderate CKD, the duration of disease rather than estimated glomerular filtration rate was associated with impaired attention regulation and inhibitory control.

Neurocognition in children with autosomal recessive polycystic kidney disease in the CKiD cohort study.

BACKGROUND: Autosomal recessive polycystic kidney disease (ARPKD) is an inherited disorder characterized by enlarged, cystic kidneys with progressive chronic kidney disease (CKD), systemic hypertension, and congenital hepatic fibrosis. Children with ARPKD can have early onset CKD and severe hypertension, both of which are known to have adverse neurocognitive effects. The objectives of this study were (1) to determine whether ARPKD patients have greater neurocognitive deficits compared to that of children with other causes of CKD, and (2) to examine the relative prevalence of hypertension in ARPKD, a known risk factor for neurocognitive dysfunction. METHODS: We performed a cross-sectional, control-matched analysis of 22 ARPKD patients with mild-to-moderate CKD in the Chronic Kidney Disease in Children (CKiD) cohort study, compared with a control group of 44 children with other causes of CKD, matched based on glomerular filtration rate, age at study entry, and age at diagnosis. RESULTS: Children with ARPKD in this cohort had neurocognitive functioning comparable to children with other causes of CKD in domains of intellectual functioning, academic achievement, attention regulation, executive functioning, and behavior. Blood pressure parameters were similar between the two groups; however, ARPKD patients required a significantly greater number of antihypertensive medications to achieve similar BP levels. CONCLUSIONS: ARPKD patients are potentially at risk for neurocognitive dysfunction due to early onset CKD and more severe hypertension. However, this study of children with mild-to-moderate CKD in the CKiD cohort did not demonstrate increased risk in children with ARPKD compared to children with other causes of CKD. Further studies are needed to determine if these findings are applicable to children with more severe manifestations of ARPKD.

The impact of short stature on health-related quality of life in children with chronic kidney disease.

OBJECTIVES: To compare the health-related quality of life (HRQoL) of children with chronic kidney disease (CKD) and short stature (SS) with that of children with CKD and normal height (NH), to evaluate the impact of catch-up growth and growth hormone (GH) use on HRQoL, and to describe the concordance of perceptions of HRQoL between children with SS and NH and their parents. STUDY DESIGN: Four hundred eighty-three children and/or parents enrolled in the multicenter Chronic Kidney Disease in Children study who had completed the Pediatric Quality of Life Inventory (Version 4.0) on at least 2 Chronic Kidney Disease in Children study visits composed this substudy population. Participants were dichotomized into NH or SS groups. The demographic characteristics that varied at baseline (sex, glomerular filtration rate, and parent education) were controlled for in the main analysis evaluating the impact of catch-up growth and use of GH on HRQoL. RESULTS: Multivariate modeling (controlling for confounding variables) revealed a significant association between both catch-up growth and GH use on parent-proxy reports of child physical functioning (P < .05) and social functioning (P < .05). Older children with CKD (15-17 years old) had significantly higher ratings than their parents on the Pediatric Quality of Life Inventory Physical, Emotional, Social, and School Functioning scales compared with younger children (8-14 years old). CONCLUSION: The finding that height gains and GH use are associated with increases in physical and social functioning by parent report provides additional support for interventions to improve height in children with CKD. The importance of evaluating both the parent and child perceptions of HRQoL is supported by our results.

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.

Sleep and fatigue symptoms in children and adolescents with CKD: a cross-sectional analysis from the chronic kidney disease in children (CKiD) study.

BACKGROUND: Although symptoms of sleepiness and fatigue are common in adults with chronic kidney disease (CKD), little is known about the prevalence of these symptoms in children with CKD. STUDY DESIGN: Cross-sectional analysis within a cohort study. SETTING & PARTICIPANTS: We describe the frequency and severity of sleep problems and fatigue and assess the extent of their association with measured glomerular filtration rate (mGFR) and health-related quality of life (HRQOL) in 301 participants of the Chronic Kidney Disease in Children cohort. OUTCOMES & MEASUREMENTS: Sleep and fatigue-related items from the Pediatric Quality of Life Inventory 4.0 Generic Scales and the CKD-related Symptoms List were used. RESULTS: Median mGFR was 42.0 mL/min/1.73 m(2) (25th-75th percentiles, 31.2-53.2), and median age was 13.9 years (25th-75th percentiles, 10.8-16.2). Children with mGFR of 40-<50, 30-<40, or <30 mL/min/1.73 m(2) had 2.07 (95% CI, 1.05-4.09), 2.35 (95% CI, 1.17-4.72), and 2.59 (95% CI, 1.15-5.85) higher odds of having more severe parent reports of low energy than children with mGFR > or = 50 mL/min/1.73 m(2). Compared with participants with mGFR > or = 50 mL/min/1.73 m(2), those with mGFR < 30 mL/min/1.73 m(2) had 3.92 (95% CI, 1.37-11.17) higher odds of reporting more severe weakness, and those with mGFR of 40-<50 mL/min/1.73 m(2) had 2.95 (95% CI, 1.26-6.88) higher odds of falling asleep during the day. Low energy, trouble sleeping, and weakness were associated with lower HRQOL scores. LIMITATIONS: Symptoms of sleep and fatigue represent the child's or parent's perception of symptom severity, whereas individual items can lead to imprecise measurements of sleep and fatigue. CONCLUSIONS: Lower mGFR was associated with increased weakness, low energy, and daytime sleepiness. Furthermore, a strong association between trouble sleeping, low energy, and weakness with decreases in overall HRQOL was observed. Detection and treatment of poor sleep and fatigue may improve the development and HRQOL of children and adolescents with CKD.

Parent perspectives of health related quality of life in adolescents with chronic kidney disease due to underlying urological disorders: an assessment using the Child Health Questionnaire-Parent Form 50.

PURPOSE: Little is known about health related quality of life in adolescents with chronic kidney disease due to urological anomalies. We assessed generic health related quality of life in this population using a validated parent proxy instrument. MATERIALS AND METHODS: In this multicenter prospective cohort study the Child Health Questionnaire-Parent Form 50, a generic health related quality of life parent proxy instrument, was administered to 92 parents of adolescents 10 to 18 years old with chronic kidney disease. Mean summary measure and scale scores in adolescents with urological anomalies were compared to scores in those with other causes of kidney disease and in a representative American population sample. RESULTS: The cohort included 35 adolescents with an underlying diagnosis of congenital urological anomaly and 57 with another cause of kidney disease. There were no significant differences in mean scale or summary measure scores between the 2 diagnostic groups. When compared to a representative population sample, adolescents with congenital urological anomalies scored significantly worse on the questionnaire physical summary measure (44.5, 95% CI 39.9-49.1 vs 52.0, 95% CI 51.1-52.9, p = 0.002), and on the Child Health Questionnaire scales physical functioning, role physical, general health perceptions, family activities and parental emotional impact. CONCLUSIONS: As assessed by Child Health Questionnaire-Parent Form 50, parents reported that adolescents with chronic kidney disease due to urological disorders scored lower on the physical summary measure than a population based reference sample and they reported a negative effect on family activities and parental emotional well-being. These findings suggest that the Child Health Questionnaire-Parent Form 50 could provide a family based assessment of generic health related quality of life in adolescents with urological disorders.

Quality of life for children with chronic kidney disease.

Medical care advancements for children with chronic kidney disease (CKD) receiving hemodialysis, peritoneal dialysis, or with a renal transplant have resulted in relatively improved long-term patient survival compared with adult patients with CKD. Optimal care for the pediatric patient with CKD requires attention not only to medical management, but also the psychosocial and developmental factors that either will ensure or prevent a pediatric patient's successful transition into adulthood. We review the range of issues that impact pediatric CKD patients' health-related quality of life (HRQOL), the history of pediatric CKD patients' HRQOL investigation, and the instruments currently available to assess HRQOL.

Neurocognitive, Social-Behavioral, and Adaptive Functioning in Preschool Children with Mild to Moderate Kidney Disease.

OBJECTIVE: The negative impact of end-stage kidney disease on cognitive function in children is well established, but no studies have examined the neurocognitive, social-behavioral, and adaptive behavior skills of preschool children with mild to moderate chronic kidney disease (CKD). METHOD: Participants included 124 preschool children with mild to moderate CKD, aged 12 to 68 months (median = 3.7 years), and an associated mean glomerular filtration rate (GFR) of 50.0 mL·min·1.73 m. In addition to level of function and percent of participants scoring ≥1 SD below the test mean, regression models examined the associations between biomarkers of CKD (GFR, anemia, hypertension, seizures, and abnormal birth history), and developmental level/IQ, attention regulation, and parent ratings of executive functions, social-behavior, and adaptive behaviors. RESULTS: Median scores for all measures were in the average range; however, 27% were deemed at risk for a developmental level/IQ <85, 20% were at-risk for attention variability, and parent ratings indicated 30% and 37% to be at risk for executive dysfunction and adaptive behavior problems, respectively. Approximately 43% were deemed at risk on 2 or more measures. None of the disease-related variables were significantly associated with these outcomes, although the presence of hypertension approached significance for attention variability (p < .09). Abnormal birth history and lower maternal education were significantly related to lower developmental level/IQ; seizures were related to lower parental ratings of executive function and adaptive behavior; and abnormal birth history was significantly related to lower ratings of adaptive behavior. When predicting risk status, the logistic regression did evidence both higher GFR and the lack of anemia to be associated with more intact developmental level/IQ. CONCLUSION: These findings suggest relatively intact functioning for preschool children with mild to moderate CKD, but the need for ongoing developmental surveillance in this population remains warranted, particularly for those with abnormal birth histories, seizures, and heightened disease severity.

Casual blood pressure and neurocognitive function in children with chronic kidney disease: a report of the children with chronic kidney disease cohort study.

BACKGROUND AND OBJECTIVES: Children with chronic kidney disease (CKD) are at risk for cognitive dysfunction, and over half have hypertension. Data on the potential contribution of hypertension to CKD-associated neurocognitive deficits in children are limited. Our objective was to determine whether children with CKD and elevated BP (EBP) had decreased performance on neurocognitive testing compared with children with CKD and normal BP. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This was a cross-sectional analysis of the relation between auscultatory BP and neurocognitive test performance in children 6 to 17 years enrolled in the Chronic Kidney Disease in Children (CKiD) project. RESULTS: Of 383 subjects, 132 (34%) had EBP (systolic BP and/or diastolic BP ≥90(th) percentile). Subjects with EBP had lower mean (SD) scores on Wechsler Abbreviated Scales of Intelligence (WASI) Performance IQ than those with normal BP (normal BP versus EBP, 96.1 (16.7) versus 92.4 (14.9), P = 0.03) and WASI Full Scale IQ (97.0 (16.2) versus 93.4 (16.5), P = 0.04). BP index (subject's BP/95(th) percentile BP) correlated inversely with Performance IQ score (systolic, r = -0.13, P = 0.01; diastolic, r = -0.19, P < 0.001). On multivariate analysis, the association between lower Performance IQ score and increased BP remained significant after controlling for demographic and disease-related variables (EBP, ß = -3.7, 95% confidence interval [CI]: -7.3 to -0.06; systolic BP index, ß = -1.16 to 95% CI: -2.1, -0.21; diastolic BP index, ß = -1.17, 95% CI: -1.8 to -0.55). CONCLUSIONS: Higher BP was independently associated with decreased WASI Performance IQ scores in children with mild-to-moderate CKD.

Neurocognitive functioning of children and adolescents with mild-to-moderate chronic kidney disease.

BACKGROUND AND OBJECTIVES: Few data exist on the neurocognitive functioning of children with mild-to-moderate chronic kidney disease (CKD). The primary objectives of this paper are (1) to determine the neurocognitive status in this population and (2) to identify sociodemographic and health-status variables associated with neurocognitive functioning. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This was a cross-sectional study of 368 children, aged 6 to 16 years, from the Chronic Kidney Disease in Children (CKiD) cohort. Median iGFR was 43 ml/min per 1.73 m(2), and the median duration of CKD was 8.0 years. Approximately 26% had underlying glomerular disease. Measures of intelligence, academic achievement, attention regulation, and executive functioning were obtained at study entry. The prevalence of neurocognitive deficits was determined by comparing participant scores on each measure of neurocognitive functioning with normative data. The association between hypothesized predictors of neurocognitive dysfunction was evaluated using multivariate regression analyses. RESULTS: Neurocognitive functioning was within the average range for the entire group; however, 21% to 40% of participants scored at least one SD below the mean on measures of intelligence quotient (IQ), academic achievement, attention regulation, or executive functioning. Higher iohexol-based GFR (iGFR) predicted a lesser risk for poor performance on measures of executive function. Participants having elevated proteinuria (i.e., urine protein/creatinine >2) scored lower on verbal IQ, full-scale IQ, and attention variability than those without elevated proteinuria. CONCLUSIONS: Whereas most children with mild-to-moderate CKD have no major neurocognitive deficits, a substantial percentage did show neurocognitive dysfunction that places them at risk for poor long-term educational and occupational outcomes.

Health-related quality of life of children with mild to moderate chronic kidney disease.

OBJECTIVE: To compare the health-related quality of life (HRQoL) of children with chronic kidney disease (CKD) with healthy children; to evaluate the association between CKD severity and HRQoL; and to identity demographic, socioeconomic, and health-status variables that are associated with impairment in HRQoL in children with mild to moderate CKD. METHODS: This was a cross-sectional assessment of HRQoL in children who were aged 2 to 16 and had mild to moderate CKD using the Pediatric Inventory of Quality of Life Core Scales (PedsQL). Overall HRQoL and PedsQL domain means for parents and youth were compared with previously published norms by using independent sample t tests. Study participants were categorized by kidney disease stage (measured by iohexol-based glomerular filtration rate [iGFR]), and group differences in HRQoL were evaluated by using analysis of variance and Cuzick trend tests. The association between hypothesized predictors of HRQoL and PedsQL scores was evaluated with linear and logistic regression analyses. RESULTS: The study sample comprised 402 participants (mean age: 11 years, 60% male, 70% white, median iGFR: 42.5 mL/min per 1.73 m(2), median CKD duration: 7 years). Youth with CKD had significantly lower physical, school, emotional, and social domain scores than healthy youth. iGFR was not associated with HRQoL. Longer disease duration and older age were associated with higher PedsQL scores in the domains of physical, emotional, and social functioning. Older age was associated with lower school domain scores. Maternal education > or =16 years was associated with higher PedsQL scores in the domains of physical, school, and social functioning. Short stature was associated with lower scores in the physical functioning domain. CONCLUSIONS: Children with mild to moderate CKD, in comparison with healthy children, reported poorer overall HRQoL and poorer physical, school, emotional, and social functioning. Early intervention to improve linear growth and to address school functioning difficulties is recommended.