Observations of Positive Parenting from Online Parent-Child Interactions at Age 1.

Objective: Brief, reliable, and cost-effective methods to assess parenting are critical for advancing parenting research. Design: We adapted the Three Bags task and Parent Child Interaction Rating System (PCIRS) for rating online visits with 219 parent-child dyads (White, n = 104 [47.5%], Black, n = 115 [52.5%]) and combined the video data with survey data collected during pregnancy and when children were aged 1. Results: The PCIRS codes of positive regard, stimulation of child cognitive development, and sensitivity showed high reliability across the three parent-child interaction tasks. A latent positive parenting factor combining ratings across codes and tasks showed good model fit, which was similar regardless of parent self-identified race or ethnicity, age, socioeconomic disadvantage, marital/partnered status, and parity, as well as methodological factors relevant to the online video assessment method (e.g., phone vs. laptop/tablet). In support of construct validity, observed positive parenting was related to parent-reported positive parenting and child socioemotional development. Finally, parent reports of supportive relationships in pregnancy, but not neighborhood safety or pandemic worries, were prospectively related to higher positive parenting observed at age 1. With the exception of older parental age and married/partnered status, no other parent, child, sociodemographic, or methodological variables were related to higher overall video exclusions across tasks. Conclusions: PCIRS may provide a reliable approach to rate positive parenting at age 1, providing future avenues for developing more ecologically valid assessments and implementing interventions through online encounters that may be more acceptable, accessible, or preferred among parents of young children.

The Influence of Pandemic-Related Worries During Pregnancy on Child Development at 12 Months.

The COVID-19 pandemic has been linked to increased risk for perinatal anxiety and depression among parents, as well as negative consequences for child development. Less is known about how worries arising from the pandemic during pregnancy are related to later child development, nor if resilience factors buffer negative consequences. The current study addresses this question in a prospective longitudinal design. Data was collected from a sub-study (n = 184) of a longitudinal study of pregnant individuals (total n = 1173). During pregnancy (April 17-July 8, 2020) and the early postpartum period (August 11, 2020-March 2, 2021), participants completed online surveys. At 12 months postpartum (June 17, 2021-March 23, 2022), participants completed online surveys and a virtual laboratory visit, which included parent-child interaction tasks. We found more pregnancy-specific pandemic worries were prospectively related to lower levels of child socioemotional development based on parent report (B = - 1.13, SE = .43, p = .007) and observer ratings (B = - 0.13, SE = .07, p = .045), but not to parent-reported general developmental milestones. Parental emotion regulation in the early postpartum period moderated the association between pregnancy-specific pandemic worries and child socioemotional development such that pregnancy-specific pandemic worries did not relate to worse child socioemotional development among parents with high (B = - .02, SE = .10, t = - .14, p = .89) levels of emotion regulation. Findings suggest the negative consequences of parental worry and distress during pregnancy on the early socioemotional development of children in the context of the COVID-19 pandemic. Results highlight that parental emotion regulation may represent a target for intervention to promote parental resilience and support optimized child development.

Development of Iron Status Measures during Youth: Associations with Sex, Neighborhood Socioeconomic Status, Cognitive Performance, and Brain Structure.

BACKGROUND: Iron is essential to brain function, and iron deficiency during youth may adversely impact neurodevelopment. Understanding the developmental time course of iron status and its association with neurocognitive functioning is important for identifying windows for intervention. OBJECTIVES: This study aimed to characterize developmental change in iron status and understand its association with cognitive performance and brain structure during adolescence using data from a large pediatric health network. METHODS: This study included a cross-sectional sample of 4899 participants (2178 males; aged 8-22 y at the time of participation, M [SD] = 14.24 [3.7]) who were recruited from the Children's Hospital of Philadelphia network. Prospectively collected research data were enriched with electronic medical record data that included hematological measures related to iron status, including serum hemoglobin, ferritin, and transferrin (33,015 total samples). At the time of participation, cognitive performance was assessed using the Penn Computerized Neurocognitive Battery, and brain white matter integrity was assessed using diffusion-weighted MRI in a subset of individuals. RESULTS: Developmental trajectories were characterized for all metrics and revealed that sex differences emerged after menarche such that females had reduced iron status relative to males [all R2partial > 0.008; all false discovery rates (FDRs) < 0.05]. Higher socioeconomic status was associated with higher hemoglobin concentrations throughout development (R2partial = 0.005; FDR < 0.001), and the association was greatest during adolescence. Higher hemoglobin concentrations were associated with better cognitive performance during adolescence (R2partial = 0.02; FDR < 0.001) and mediated the association between sex and cognition (mediation effect = -0.107; 95% CI: -0.191, -0.02). Higher hemoglobin concentration was also associated with greater brain white matter integrity in the neuroimaging subsample (R2partial = 0.06, FDR = 0.028). CONCLUSIONS: Iron status evolves during youth and is lowest in females and individuals of low socioeconomic status during adolescence. Diminished iron status during adolescence has consequences for neurocognition, suggesting that this critical period of neurodevelopment may be an important window for intervention that has the potential to reduce health disparities in at-risk populations.

The Influence of Pandemic-Related Worries During Pregnancy on Child Development at 12 Months.

The COVID-19 pandemic has been linked to increased risk for perinatal anxiety and depression among parents, as well as negative consequences for child development. Less is known about how worries arising from the pandemic during pregnancy are related to later child development, nor if resilience factors buffer negative consequences. The current study addresses this question in a prospective longitudinal design. Data was collected from a sub-study ( n = 184) of a longitudinal study of pregnant individuals (total n = 1,173). During pregnancy (April 17-July 8, 2020) and the early postpartum period (August 11, 2020-March 2, 2021), participants completed online surveys. At 12 months postpartum (June 17, 2021-March 23, 2022), participants completed online surveys and a virtual laboratory visit, which included parent-child interaction tasks. We found more pregnancy-specific pandemic worries were prospectively related to lower levels of child socioemotional development based on parent report (B=-1.13, SE = .43, p = .007) and observer ratings (B=-0.13, SE = .07, p = .045), but not to parent-reported general developmental milestones. Parental emotion regulation in the early postpartum period moderated the association between pregnancy-specific pandemic worries and child socioemotional development such that pregnancy-specific pandemic worries did not related to worse child socioemotional development among parents with high (B=-.02, SE = .10, t=-.14, p = .89) levels of emotion regulation. Findings suggest the negative consequences of parental worry and distress during pregnancy on the early socioemotional development of children in the context of the COVID-19 pandemic. Results highlight that parental emotion regulation may represent a target for intervention to promote parental resilience and support optimized child development.

Sleep-related breathing disorders and cardiometabolic risk factors in pediatric kidney transplant recipients.

BACKGROUND: SRBDs have been shown to increase the risk of cardiovascular disease, which is a significant cause of mortality in kidney transplant recipients. Few studies have investigated the association between SRBDs and cardiometabolic risk factors in pediatric kidney transplant recipients. METHODS: This was a cross-sectional study of pediatric kidney transplant recipients using baseline cardiometabolic data from a previous clinical trial (NCT01007994). Parents/guardians of pediatric kidney transplant recipients filled out 22-item PSQ. A score greater than 33% was defined as a diagnosis of a SRBD. Fisher's exact test, Mann-Whitney U test, and regressions were used to determine associations. RESULTS: Among the 58 transplant recipients enrolled, 14.80% (n = 8) of participants identified as Black and 40.7% (n = 22) were male. The median age was 13 (IQR 8.25, 17) years and median number of years post-transplant for participants was 2 (IQR 1, 4). The prevalence of SRBDs was 26% (n = 14). The presence of a SRBD was associated with abnormalities in multiple cardiometabolic risk factors including total cholesterol level (ß = 23.63; 95% CI 3.58-43.67), LDL level (ß = 24.94; 95% CI 6.37-43.50), triglyceride level (ß = 54.62; 95% CI 8.74-100.50), and LVH (OR = 5.12; 95% CI 1.12-23.45) when adjusted for age, sex, and race. CONCLUSIONS: Similar to associations reported in the general pediatric and general CKD populations, SRBD is associated with increased cardiometabolic risk in pediatric kidney transplant recipients.

Left Ventricular Measurements and Strain in Pediatric Patients Evaluated for Systemic Hypertension and the Effect of Adequate Anti-hypertensive Treatment.

Pediatric hypertension (HTN) is an epidemic that is associated with HTN in adulthood and adverse cardiovascular outcomes. We hypothesized that children with HTN would have left ventricular (LV) hypertrophy and abnormal LV global longitudinal strain (GLS) on echocardiogram and that these values would differ by weight, race, and HTN treatment. Data were collected from first visits to the HTN Program from 12/2011 to 9/2018, excluding patients with cardiac disease or heart transplantation. LV measurements including LV mass index (LVMI), LV GLS, and diastolic indices were compared between groups. Multivariable logistic regression was used to identify risk factors for an abnormal LVMI. There were 212 patients with an interquartile age range of 13-18 years. On univariate analysis, LVMI was higher in hypertensive, obese, and African American patients. LV strain was less negative in obese and African American patients. Adequately treated patients with HTN had a higher LVMI and a higher E/e' ratio compared to patients with no HTN. On multivariate analysis, only obesity was associated with an LVMI ≥ 95th percentile (OR 2.9, 95% CI 1.4, 5.8). LVMI is higher in hypertensive, obese, and African American patients; however, in the multivariate analysis, obesity was the only independent risk factor for an abnormal LVMI. LVMI was still higher in those adequately treated for HTN compared to patients without HTN, possibly due to concomitant obesity. Future studies should focus on subclinical changes in LV performance seen in obese and hypertensive patients and the impact on long-term health.

Decreased Neural Connectivity in the Default Mode Network Among Youth and Young Adults With Chronic Kidney Disease.

An increasing amount of literature has indicated that chronic kidney disease (CKD) is associated with cognitive deficits that increase with worsening disease severity. Although abnormalities in brain structure have been widely documented, few studies to date have examined the functioning of brain areas associated with the specific cognitive domains affected by CKD (namely, attention and executive functions). Furthermore, few studies have examined functional connectivity among CKD youth who are relatively early in the course of the disease. The present study used functional magnetic resonance imaging to examine the resting state connectivity in 67 youth with CKD (mean age, 17 y) and 58 age-matched healthy controls. Using seed-based multiple regression, decreased connectivity was observed within the anterior cingulate portion of the default mode network. In addition, decreased connectivity within the dorsolateral prefrontal cortex, paracingulate gyrus, and frontal pole were correlated significantly with disease severity. These data indicate that connectivity deficits in circuits implementing attentional processes may represent an early marker for cognitive decline in CKD.

The Disproportionate Burden of the COVID-19 Pandemic Among Pregnant Black Women.

The COVID-19 pandemic has disproportionately impacted the well-being of vulnerable populations in the US, including Black people. The impact on pregnant women is of special concern for the intrauterine and post-natal development of their offspring. We evaluated in an online survey a sample of 913 pregnant women, 216 Black, 571 White, 126 Other, during a 2-week stay-at-home mandate in the Philadelphia region. We applied logistic regression models and analysis of covariance to examine general and pregnancy-specific worries and negative consequences arising from the COVID-19 pandemic, symptoms of anxiety and depression, and resilience. Black pregnant women reported greater likelihood of having their employment negatively impacted, more concerns about a lasting economic burden, and more worries about their prenatal care, birth experience, and post-natal needs. In the full sample, 11.1% of women met screening criteria for anxiety and 9.9% met criteria for depression. Black women were more likely to meet criteria for depression than White women, but this difference was not significant accounting for covariates. Resilience factors including self-reliance and emotion regulation were higher in Black women. Racial disparities related to COVID-19 in pregnant women can advance the understanding of pregnancy related stressors and improve early identification of mental health needs.

Restoration of nocturnal blood pressure dip and reduction of nocturnal blood pressure with evening anti-hypertensive medication administration in pediatric kidney transplant recipients: A pilot randomized clinical trial.

Non-dipping and nocturnal hypertension are commonly found during ABPM in pediatric kidney transplant recipients. These entities are independently associated with increased cardiovascular disease risk in adults. Kidney transplant recipients aged 5-21 years with eGFR > 30 mL/min/1.73 m2 and ABPM demonstrating non-dipping status and normal daytime BP were randomized to intervention (short acting BP medication added in the evening) or control (no medication change) in this pilot, randomized, open-label, blinded end-point clinical trial. ABPM, echocardiography, and PWV were performed at baseline, 3 months, and 6 months. The trial included 17 intervention and 16 control participants. Conversion to dipper status occurred in 53.3% vs 7.7% (P = .01) at 6 months for intervention and controls, respectively. Systolic dip was greater in the intervention group compared to controls (10.9 ± 4.5 vs 4.2 ± 4.6, P = .001), and average systolic nighttime BP was significantly lower in the intervention group (106 ± 8.3 vs 114.9 ± 9.5 mm Hg, P = .01) at 6 months. There were no significant differences in LVMI, PWV, or eGFR between groups. Within-group changes in the intervention group demonstrated improvements in non-dippers, dipping, systolic nighttime BP and nighttime BP load. Restoration of nocturnal dip and improvement in nocturnal BP were observed in the population following chronotherapy. Future studies are needed with larger sample sizes over a longer period of time to delineate the long-term effect of improved nocturnal dip on target organ damage.

Clinical Innovation: A Multidisciplinary Program for the Diagnosis and Treatment of Systemic Hypertension in Children and Adolescents.

Pediatric systemic hypertension (HTN) is underdiagnosed and undertreated. The Divisions of Cardiology and Nephrology at our institution developed a comprehensive outpatient HTN program to (1) screen children at risk for HTN, (2) assess cardiovascular health, and (3) optimize medical management. We report our findings during all initial visits (n = 304) from December 2011 to September 2018. Of the cohort, 38% were obese and 36% reported little to no exercise. More than half of patients ≥11 years old did not have recommended lipid screening. When evaluating ambulatory blood pressure monitoring results, clinic blood pressure did not accurately diagnose patients with or without HTN and many patients on antihypertensive medications were inadequately treated. Visit recommendations included addition of or changes to antihypertensive medication in 35% of patients. A multidisciplinary program dedicated to pediatric HTN helps screen patients who are at risk. Ambulatory blood pressure monitoring identifies HTN in patients with normal clinic blood pressure and those on antihypertensive medication.

Depression and neurocognitive dysfunction in pediatric and young adult chronic kidney disease.

BACKGROUND: Depression affects 7-35% of children with chronic kidney disease (CKD), and in adults with CKD, the presence of depression links to poorer medical outcomes, social functioning difficulties, and neurocognitive impairments. The relationship between depression and neurocognitive function in youth with CKD is unclear. We sought to identify factors associated with depression in youth with CKD and to determine whether depression affects neurocognitive performance. METHODS: We conducted cross-sectional analyses in 71 CKD and 64 control participants aged 8 to 25 years who completed depression inventories and neurocognitive assessments as part of the Neurocognitive Assessment and Magnetic Resonance Imaging Analysis of Children and Young Adults with CKD Study. In the CKD group, multivariable logistic regression analysis determined associations between clinical and demographic factors and depression. In the full study cohort, multivariable linear regression analyses, including an interaction term between CKD status and depression evaluated the effect of depression on 11 neurocognitive outcome domains. RESULTS: Obesity significantly associated with depression in the CKD group (OR 10.25, P = 0.01). In adjusted analyses, depressed youth with CKD scored worse than non-depressed CKD participants by 0.6-1.0 standard deviations in 5 neurocognitive domains: attention, visual memory, visual-spatial, visual working memory, and problem solving. CONCLUSIONS: CKD youth with obesity are more likely to be depressed, and those who are depressed exhibit worse neurocognitive performance. Depression may represent a therapeutic target to improve neurocognitive performance in youth with CKD.

Effect of blood T1 estimation strategy on arterial spin labeled cerebral blood flow quantification in children and young adults with kidney disease.

PURPOSE: To compare blood T1 estimation approaches used for quantifying cerebral blood flow (CBF) with arterial spin labeled (ASL) perfusion MRI in a developmental cohort of chronic kidney disease (CKD) patients with anemia and a control group. METHODS: 61 patients with CKD and 47 age-matched control subjects were studied. Blood T1 approaches included: (1) a fixed value, (2) estimation based on measured hematocrit (Hct), and (3) estimation based on Age+Sex using a published formula. Resulting T1 and CBF values were compared along with group, age and sex effects. RESULTS: Highly significant group differences in CBF using fixed blood T1 were reduced when Hct-corrected blood T1 was used, and were eliminated entirely when using the Age+Sex estimated approach. In the control cohort, fixed T1 method showed the strongest correlations of CBF with age and sex. Hct-corrected T1 preserved a significant correlation between CBF and age and sex, while Age+Sex estimated T1 produced a poor fit of CBF with age and sex. CONCLUSIONS: Blood T1 estimation method can confound the interpretation of CBF changes measured using ASL MRI in patients with CKD. Blood T1 should ideally be corrected for hematocrit effects in clinical populations with anemia.

Regional Cerebral Blood Flow in Children and Young Adults with Chronic Kidney Disease.

Purpose To investigate the pathophysiologic effects of chronic kidney disease (CKD) on brain function in children with CKD by correlating cerebral blood flow (CBF) with clinical and behavioral indexes. Materials and Methods In this prospective study, 73 pediatric patients with CKD (mean age, 15.80 years ± 3.63; range, 9-25 years) and 57 control subjects (mean age, 15.65 years ± 3.76; range, 9-25 years) were recruited. CBF measurements were acquired with an MRI arterial spin labeling scheme. Neurocognitive measurements were performed with traditional and computerized neurocognitive batteries. Clinical data were also collected. Group-level global and regional CBF differences between patients with CKD and control subjects were assessed. Regression analyses were conducted to evaluate the associations among regional CBF, clinical variables, and cognitive performance. Results Patients with CKD showed higher global CBF compared with control subjects that was attributable to reduced hematocrit level (mean, 60.2 mL/100 g/min ± 9.0 vs 56.5 mL/100 g/min ± 8.0, respectively). White matter CBF showed correlation with blood pressure (r = 0.244, P = .039), a finding suggestive of altered cerebrovascular autoregulation. Regional CBF differences between patients and control subjects included regions in the "default mode" network. In patients with CKD, positive extrema in the precuneus showed a strong correlation with executive function (ρ = 0.608, P = .001). Conclusion Systemic effects of estimated glomerular filtration rate, hematocrit level, and blood pressure on CBF and alterations in regional CBF may reflect impaired brain function underlying neurocognitive symptoms in CKD. These findings further characterize the nature of alterations in brain physiologic features in children, adolescents, and young adults with CKD.

Brain Magnetic Resonance Imaging Findings in Children and Young Adults With CKD.

BACKGROUND: The neuroanatomic basis for cognitive impairment in chronic kidney disease (CKD) is incompletely characterized. We performed advanced quantitative structural magnetic resonance imaging (MRI) to determine whether CKD affects brain structure and whether poorer neurocognitive performance in CKD is associated with structural brain differences. STUDY DESIGN: Cross-sectional. SETTING & PARTICIPANTS: 85 individuals with CKD stages 2 to 5 and 63 healthy controls, aged 8 to 25 years PREDICTORS: CKD versus control, estimated glomerular filtration rate (eGFR), and kidney transplant status were analyzed as predictors of MRI findings. MRI volumes in 19 prespecified regions of gray matter (GM), white matter (WM), and cerebrospinal fluid were analyzed as predictors of neurocognitive performance (median z scores) in 7 prespecified domains. OUTCOMES: 19 prespecified brain regions of interest (ROIs) in 7 prespecified domains. Neurocognitive performance in 7 prespecified domains. MEASUREMENTS: ROI volumes were compared in CKD versus controls using unadjusted t tests and analysis of covariance (ANCOVA). Associations of ROI volumes with eGFR and kidney transplant status in participants with CKD were analyzed using ANCOVA and linear regression. Associations of neurocognitive performance and ROI volumes were analyzed by linear regression. RESULTS: Participants with CKD had lower whole-brain, cortical, and left parietal GM volumes than controls in unadjusted analyses, but no differences were found in adjusted analysis. In participants with CKD, lower eGFR was associated with higher WM volume in whole-brain (P=0.05) and frontal (P=0.04) ROIs, but differences were not significant after multiple comparisons correction. Kidney transplant recipients had lower GM volumes in whole-brain (P=0.01; Q=0.06), frontal (P=0.02; Q=0.08), and left and right parietal (P=0.01; Q=0.06; and P=0.03; Q=0.1) ROIs and higher whole-brain WM volume (P=0.04; Q=0.1). Neurocognitive performance in the CKD group was not associated with ROI volumes. LIMITATIONS: Unable to assess changes in brain structure and kidney function over time; analysis limited to prespecified ROIs and neurocognitive domains. CONCLUSIONS: CKD in children and young adults may be associated with lower GM and higher WM volumes in some ROIs. Differences were relatively subtle in the CKD group as a whole, but were more prominent in recipients of a kidney transplant. However, neurocognitive performance was not explained by differences in brain ROI volumes, suggesting a functional rather than structural basis for neurocognitive impairment in CKD.

Neurocognitive Dysfunction in Children, Adolescents, and Young Adults With CKD.

BACKGROUND: Neurocognitive dysfunction is a known complication in children with chronic kidney disease (CKD). However, less is known about putative mechanisms or modifiable risk factors. The objective of this study was to characterize and determine risk factors for cognitive dysfunction in children, adolescents, and young adults with CKD compared with controls. STUDY DESIGN: Cross-sectional study. SETTING & PARTICIPANTS: The Neurocognitive Assessment and Magnetic Resonance Imaging Analysis of Children and Young Adults With Chronic Kidney Disease (NiCK) Study included 90 individuals aged 8 to 25 years with CKD compared with 70 controls. PREDICTORS: CKD versus control, estimated glomerular filtration rate (eGFR), ambulatory blood pressure. OUTCOMES: Performance on neurocognitive assessment with relevant tests grouped into 11 domains defined a priori by expert opinion. Results of tests were converted to age-normalized z scores. MEASUREMENTS: Each neurocognitive domain was analyzed through linear regression, adjusting for eGFR and demographic and clinical variables. For domains defined by multiple tests, the median z score of tests in that domain was used. RESULTS: We found significantly poorer performance in multiple areas of neurocognitive function among individuals with CKD compared with controls. Particular deficits were seen in domains related to attention, memory, and inhibitory control. Adjusted for demographic and clinical factors, we found lower performance in multiple domains with decreasing eGFRs (attention: ß=0.053, P=0.02; visual spatial: ß=0.062, P=0.02; and visual working memory: ß=0.069, P=0.04). Increased diastolic load and decreased diastolic nocturnal dipping on ambulatory blood pressure monitoring were independently associated with impairments in neurocognitive performance. LIMITATIONS: Unable to assess changes in neurocognitive function over time, and neurocognitive tests were grouped into predetermined neurocognitive domains. CONCLUSIONS: Lower eGFR in children, adolescents, and young adults is associated with poorer neurocognitive performance, particularly in areas of attention, memory, and inhibitory control. Hypertension identified on ambulatory blood pressure monitoring may be an important risk factor, illustrating that neurocognitive function is an area of target-organ damage in CKD.

Evaluation of Neurocognition in Youth with CKD Using a Novel Computerized Neurocognitive Battery.

BACKGROUND AND OBJECTIVES: Neurocognitive problems in CKD are well documented; time-efficient methods are needed to assess neurocognition in this population. We performed the first study of the efficient 1-hour Penn Computerized Neurocognitive Battery (CNB) in children and young adults with CKD. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We administered the Penn CNB cross-sectionally to individuals aged 8-25 years with stage 2-5 CKD (n=92, enrolled from three academic nephrology practices from 2011 to 2014) and matched healthy controls (n=69). We analyzed results from 12 tests in four domains: executive control, episodic memory, complex cognition, and social cognition. All tests measure accuracy and speed; we converted raw scores to age-specific z-scores on the basis of Philadelphia Neurodevelopmental Cohort (n=1790) norms. We analyzed each test in a linear regression with accuracy and speed z-scores as dependent variables and with (1) CKD versus control or (2) eGFR as explanatory variables, adjusted for race, sex, and maternal education. RESULTS: Patients with CKD (mean±SD eGFR, 48±25 ml/min per 1.73 m(2); mean age, 16.3±3.9 years) and controls (mean eGFR, 98±20 ml/min per 1.73 m(2); mean age, 16.0±4.0 years) were similar demographically. CKD participants had lower accuracy than controls in tests of complex cognition, with moderate to large effect sizes: -0.53 (95% confidence interval [95% CI], -0.87 to -0.19) for verbal reasoning, -0.52 (95% CI, -0.83 to -0.22) for nonverbal reasoning, and -0.64 (95% CI, -0.99 to -0.29) for spatial processing. For attention, patients with CKD had lower accuracy (effect size, -0.35 [95% CI, -0.67 to -0.03]) but faster response times (effect size, 0.44 [95% CI, 0.04 to 0.83]) than controls, perhaps reflecting greater impulsivity. Lower eGFR was associated with lower accuracy for complex cognition, facial and visual memory, and emotion identification tests. CONCLUSIONS: CKD is associated with lower accuracy in tests of complex cognition, attention, memory, and emotion identification, which related to eGFR. These findings are consistent with traditional neurocognitive testing in previous studies.

Executive Functioning in Children, Adolescents, and Young Adults with Chronic Kidney Disease.

OBJECTIVE: To compare behavior ratings of executive functioning in individuals with chronic kidney disease (CKD), using the Behavior Rating Inventory for Executive Functions (BRIEF), with a typically developing comparison group and to examine the correlation between disease severity and ratings of executive functioning. METHODS: Participants included 92 individuals with CKD (eGFR < 90 mL/min per 1.73 m), aged 8 to 25 years, recruited from nephrology clinics in both hospital and community settings. The disease severity ranged from CKD Stage II to V. The BRIEF was completed by parents for individuals younger than 18 years of age and the BRIEF-Adult was completed by individuals who were older than 18. RESULTS: For individuals with CKD younger than 18 years of age, the parent-reported BRIEF revealed significant group differences when compared with controls on the Metacognition Index and the individual scales of Initiate, Working Memory, and Plan/Organize. A large proportion of individuals with CKD were rated as being at-risk for executive dysfunction. For the individuals of 18 years of age and older, there were no significant group differences. The relationship between BRIEF ratings and disease severity was limited to a few scales across both versions of the BRIEF. CONCLUSION: This study supported the presence of executive dysfunction through a parent report, although the level of impairment was mild and its association with disease severity was related to select executive functions. Few difficulties were reported by older adolescents and young adults with CKD. It will be important for developmental-behavioral pediatricians to be cognizant of the level and pattern of executive function capabilities in their patients with CKD, and possible discrepancies with parent reports, so as to facilitate their management and transition planning.

Design and methods of the NiCK study: neurocognitive assessment and magnetic resonance imaging analysis of children and young adults with chronic kidney disease.

BACKGROUND: Chronic kidney disease is strongly linked to neurocognitive deficits in adults and children, but the pathophysiologic processes leading to these deficits remain poorly understood. The NiCK study (Neurocognitive Assessment and Magnetic Resonance Imaging Analysis of Children and Young Adults with Chronic Kidney Disease) seeks to address critical gaps in our understanding of the biological basis for neurologic abnormalities in chronic kidney disease. In this report, we describe the objectives, design, and methods of the NiCK study. DESIGN/METHODS: The NiCK Study is a cross-sectional cohort study in which neurocognitive and neuroimaging phenotyping is performed in children and young adults, aged 8 to 25 years, with chronic kidney disease compared to healthy controls. Assessments include (1) comprehensive neurocognitive testing (using traditional and computerized methods); (2) detailed clinical phenotyping; and (3) multimodal magnetic resonance imaging (MRI) to assess brain structure (using T1-weighted MRI, T2-weighted MRI, and diffusion tensor imaging), functional connectivity (using functional MRI), and blood flow (using arterial spin labeled MRI). Primary analyses will examine group differences in neurocognitive testing and neuroimaging between subjects with chronic kidney disease and healthy controls. Mechanisms responsible for neurocognitive dysfunction resulting from kidney disease will be explored by examining associations between neurocognitive testing and regional changes in brain structure, functional connectivity, or blood flow. In addition, the neurologic impact of kidney disease comorbidities such as anemia and hypertension will be explored. We highlight aspects of our analytical approach that illustrate the challenges and opportunities posed by data of this scope. DISCUSSION: The NiCK study provides a unique opportunity to address key questions about the biological basis of neurocognitive deficits in chronic kidney disease. Understanding these mechanisms could have great public health impact by guiding screening strategies, delivery of health information, and targeted treatment strategies for chronic kidney disease and its related comorbidities.