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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., Author(s): Stephen R. Hooper [sup.1] , Rebecca J. Johnson [sup.2] , Arlene C. Gerson [sup.3] , Marc B. Lande [sup.4] , Shlomo Shinnar [sup.5] , Lyndsay A. Harshman [sup.6] , [...]

OBJECTIVE:To determine the change in neurocognitive test performance in children with primary hypertension after initiation of antihypertensive therapy. STUDY DESIGN:Subjects with hypertension and normotensive control subjects had neurocognitive testing at baseline and again after 1 year, during which time the subjects with hypertension received antihypertensive therapy. Subjects completed tests of general intelligence, attention, memory, executive function, and processing speed, and parents completed rating scales of executive function. RESULTS:Fifty-five subjects with hypertension and 66 normotensive control subjects underwent both baseline and 1-year assessments. Overall, the blood pressure (BP) of subjects with hypertension improved (24-hour systolic BP load: mean baseline vs 1 year, 58% vs 38%, P

ObjectiveTo compare neurocognitive test performance of children with primary hypertension with that of normotensive controls.Study designSeventy-five children (10-18 years of age) with newly diagnosed, untreated hypertension and 75 frequency-matched normotensive controls had baseline neurocognitive testing as part of a prospective multicenter study of cognition in primary hypertension. Subjects completed tests of general intelligence, attention, memory, executive function, and processing speed. Parents completed rating scales of executive function and the Sleep-Related Breathing Disorder scale of the Pediatric Sleep Questionnaire (PSQ-SRBD).ResultsHypertension and control groups did not differ significantly in age, sex, maternal education, income, race, ethnicity, obesity, anxiety, depression, cholesterol, glucose, insulin, and C-reactive protein. Subjects with hypertension had greater PSQ-SRBD scores (P = .04) and triglycerides (P = .037). Multivariate analyses showed that hypertension was independently associated with worse performance on the Rey Auditory Verbal Learning Test (List A Trial 1, P = .034; List A Total, P = .009; Short delay recall, P = .013), CogState Groton Maze Learning Test delayed recall (P = .002), Grooved Pegboard dominant hand (P = .045), and Wechsler Abbreviated Scales of Intelligence Vocabulary (P = .016). Results indicated a significant interaction between disordered sleep (PSQ-SRBD score) and hypertension on ratings of executive function (P = .04), such that hypertension heightened the association between increased disordered sleep and worse executive function.ConclusionsYouth with primary hypertension demonstrated significantly lower performance on neurocognitive testing compared with normotensive controls, in particular, on measures of memory, attention, and executive functions.

BACKGROUND: We studied whether increased systolic blood pressure (SBP), as determined by auscultatory SBP, ambulatory SBP, and the number of cardiovascular health risk indicators, are associated with neurocognition in adolescents. METHODS: This cross-sectional study included 365 adolescents (mean age, 15.5 years) from 6 academic medical centers in the United States. The sample was 59.5% male, 52.6% White, with 23.9% of the caregivers having less than or equal to a high school degree. Primary exposures included the following: auscultatory SBP, ambulatory SBP, and the number of cardiovascular risk factors. Neurocognitive outcomes comprised nonverbal IQ, attention, and parent ratings of executive functions. RESULTS: After examining the models for the effects of targeted covariates (eg, maternal education), higher auscultatory SBP was associated with lower nonverbal IQ (β=−1.39; P <0.001) and verbal attention (β=−2.39; P <0.05); higher ambulatory 24 hours. SBP (β=−21.39; P <0.05) and wake SBP (β=−21.62; P <0.05) were related to verbal attention; and all 3 ambulatory blood pressure measures were related to sustained attention accounting for small to medium amounts of variance (adjusted R2=0.08–0.09). Higher ambulatory blood pressure sleep SBP also was significantly associated with parent ratings of behavior regulation (β=12.61; P <0.05). These associations remained stable after a sensitivity analysis removed cases with hypertension. Number of cardiovascular risk factors performed similarly, with more risk factors being associated with lower nonverbal IQ (β=−1.35; P <0.01), verbal attention (β=−1.23; P <0.01), and all parent ratings of executive functions. CONCLUSIONS: Elevated SBP, even below the hypertension range, and general cardiovascular health are associated with neurocognitive outcomes in adolescents. How these findings might guide clinical care is worthy of additional study. [ABSTRACT FROM AUTHOR]

Cerebrovascular disease (stroke) is one of the ten leading causes of death in children and adolescents. Multiple etiologies, from arteriopathies to prothrombic states, can cause stroke in youth. In adult stroke, hypertension has been shown to be the single most important modifiable risk factor. Although hypertension has not been strongly identified as a risk factor in childhood stroke to date, there is preliminary evidence that suggests that hypertension may also be associated with stroke in children. In this review, we summarize the literature that may link hypertension to stroke in the young. We have identified a series of barriers and limitations in the fields of pediatric hypertension and pediatric neurology that might explain why hypertension has been overlooked in childhood stroke. We suggest that hypertension may be a relevant risk factor that, alone or in combination with other multiple factors, contributes to the development of stroke in children. Currently, there are no consensus guidelines for the management of post-stroke hypertension in children. Thus, we recommend that blood pressure be assessed carefully in every child presenting with acute stroke in order to better understand the effects of hypertension in the development and the outcome of childhood stroke. We suggest a treatment algorithm to help practitioners manage hypertension after a stroke., Author(s): Juan C. Kupferman [sup.1] , Marc B. Lande [sup.2] , Stella Stabouli [sup.3] , Dimitrios I. Zafeiriou [sup.3] , Steven G. Pavlakis [sup.1] Author Affiliations: (1) grid.416306.6, 0000 0001 [...]

Background This study aimed to determine stroke incidence and assess the association between stroke and neurocognitive functioning in children with chronic kidney disease (CKD). Methods Data was derived from the Chronic Kidney Disease in Children (CKiD) cohort study. Stroke incidence was calculated after confirming self-reports of stroke occurrence by chart review. Each participant with stroke was matched with three stroke-free participants and performance on selected neurocognitive measures was compared. Wilcoxon rank-sum tests were used to compare neurocognitive test scores. Effect size (ES) was estimated using a modified version of Cohen's U.sub.3 metric that measures the excess percentage of the stroke group worse than the median of the control group. Results Of 891 subjects, five (0.56%) had a confirmed stroke prior to study entry. Median time at risk was 15.7 years [interquartile range, 12.5-18.4]. Estimated incidence rate of history of stroke was 36.8 per 100,000 children per year (95% confidence interval 15.3, 88.5). Controls and subjects with stroke were similar in age, CKD duration, race, and maternal education. ES for many of the neurocognitive comparisons was moderate to large. Subjects in the CKID cohort with a history of stroke had lower scores on spatial span reverse, spatial span forward, and design fluency, and worse parent ratings on BRIEF Metacognition Index compared to a matched sample of children with CKD without stroke. Conclusions Children with CKD have an increased incidence of prior ischemic stroke compared to the general pediatric population. A stroke history was associated with poorer performance on neurocognitive measures., Author(s): Juan C. Kupferman [sup.1] , Matthew B. Matheson [sup.2] , Marc B. Lande [sup.3] , Joseph T. Flynn [sup.4] , Susan Furth [sup.5] , Bradley A. Warady [sup.6] , [...]

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 ([beta] = 1.59, 95% CI = 0.24 to 2.94, p < 0.02) and suggested worse behavioral symptoms ([beta] = 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 ([beta] = - 3.48, CI = - 6.79 to - 0.17, p < 0.04). Glomerular diagnosis was related to fewer ([beta] = - 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., Author(s): Rebecca J. Johnson [sup.1] , Arlene C. Gerson [sup.2] , Lyndsay A. Harshman [sup.3] , Matthew B. Matheson [sup.4] , Shlomo Shinnar [sup.5] , Marc B. Lande [sup.6] , [...]

Background Children with primary hypertension have been reported to have diminished scores in measures of cognition. However, little is known about the relative correlation between office and ambulatory blood pressure (BP) and neurocognitive test performance, and whether short-term BP variability is associated with decreased neurocognitive function. We sought to determine whether ambulatory BP monitoring (ABPM) was more strongly associated with neurocognitive test performance compared with office BP, and whether increased short-term BP variability was associated with lower neurocognitive scores. Methods Seventy-five subjects ages 10-18 years, with untreated primary hypertension, and 75 matched normotensive controls completed neurocognitive testing. All subjects had office BP and ABPM prior to neurocognitive testing. Results On multivariate analyses, there was no significant association between office BP and neurocognitive tests. However, several ABPM parameters were significantly associated with neurocognitive test scores in the lower quartile, in particular 24 h SBP load and wake systolic blood pressure (SBP) index [Rey Auditory Verbal learning Test (RAVLT) List A Trial 1, 24 h SBP load, odds ratio (OR) = 1.02, wake SBP index, OR = 1.06; List A Total, 24 h SBP load, OR = 1.02, wake SBP index, OR = 1.06; Short Delay Recall, wake SBP index, OR = 1.06; CogState Maze delayed recall, 24 h SBP load, OR = 1.03, wake SBP index, OR = 1.08; Grooved Pegboard, 24 h SBP load, OR = 1.02; all p < 0.05]. In contrast, short-term BP variability measures were not associated with neurocognitive test performance. Conclusions ABPM is superior to office BP in distinguishing hypertensive youth with lower neurocognitive test performance., Author(s): Juan C. Kupferman [sup.1] , Donald L. Batisky [sup.2] , Joshua Samuels [sup.3] , Heather R. Adams [sup.4] , Stephen R. Hooper [sup.5] , Hongyue Wang [sup.6] , Marc [...]

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 [greater than or equal to]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, β = -0.7, 95 % confidence interval (CI) -1.28 to -0.12; ARV, β = -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., Author(s): Marc B. Lande[sup.1] , Susan R. Mendley[sup.2] , Matthew B. Matheson[sup.3] , Shlomo Shinnar[sup.4] , Arlene C. Gerson[sup.5] , Joshua A. Samuels[sup.6] , Bradley A. Warady[sup.7] , Susan L. [...]

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. Keywords Autosomal recessive polycystic kidney disease * Behavior * Chronic kidney disease * Hypertension * Neurocognition * Neuropsychological, Introduction Autosomal recessive polycystic kidney disease (ARPKD, OMIM 263200) is an important genetic cause of progressive chronic kidney disease (CKD), and occurs in an estimated 1 in 20,000 live births [...]

Data on neurocognitive function in hypertensive children are limited. In this review, we summarize recent preliminary, early studies that suggest that children with elevated blood pressure demonstrate evidence of worse performance on direct neurocognitive testing, as well as evidence of executive dysfunction based on parent ratings, compared with matched normotensive comparison groups. Furthermore, hypertensive children may have increased prevalence of learning disabilities as well as a blunted cerebrovascular reactivity compared with normotensive controls. Larger, prospective studies are needed to confirm and further explore these emerging but preliminary findings. Keywords Cognition * Elevated blood pressure * Brain * Pediatric * Executive function * Memory, Introduction As pediatric hypertension is on the rise [1, 2], there has been increased interest in evaluating the impact of both the disease and its treatment on neurocognitive function. At [...]