Brain growth and development occur at peak rates in early childhood through adolescence, and for some children, this must happen in conjunction with chronic kidney disease (CKD), associated medical ...conditions, and their treatment(s). This review provides an overview of key findings to date on the topic of the brain in pediatric CKD. Here, we specifically address the topics of neuroimaging and cognition in pediatric CKD with consideration to biomarkers of disease progression that may impact cognition. Current cognitive data suggest that most children with mild to moderate CKD do not exhibit significant cognitive impairments, but, rather, the presence of somewhat lower intellectual abilities and subtle deficits in selected executive functions. Although promising, modern neuroimaging data remain inconclusive in linking cognitive findings to neuroimaging correlates in the pediatric CKD population. Certainly, it is important to note that even subtle cognitive concerns can present barriers to learning, social functioning, and overall quality of life if not appropriately recognized or addressed. Further longitudinal research utilizing concurrent and targeted cognitive and neuroimaging evaluations is warranted to better understand the impact of CKD progression on brain development and associated neurocognitive outcomes.
Posttraumatic stress disorder (PTSD) is considered a disorder of recovery where individuals fail to learn and retain extinction of the traumatic fear response. In maltreated youth, PTSD is common, ...chronic, and associated with comorbidity. Studies of extinction-related structural volumes (amygdala, hippocampus, anterior cingulate cortex (ACC), and ventral medial prefrontal cortex (vmPFC)) and this stress diathesis, in maltreated youth were not previously investigated. In this cross-sectional study, neuroanatomical volumes associated with extinction in maltreated youth with PTSD (N=31), without PTSD (N=32), and in non-maltreated healthy volunteers (n=57) were examined using magnetic resonance imaging. Groups were sociodemographically similar. Participants underwent extensive assessments for strict inclusion/exclusion criteria and DSM-IV disorders. Maltreated youth with PTSD demonstrated decreased right vmPFC volumes compared with both maltreated youth without PTSD and non-maltreated controls. Maltreated youth without PTSD demonstrated larger left amygdala and right hippocampal volumes compared with maltreated youth with PTSD and non-maltreated control youth. PTSD symptoms inversely correlated with right and left hippocampal and left amygdala volumes. Confirmatory masked voxel base morphometry analyses demonstrated greater medial orbitofrontal cortex gray matter intensity in controls than maltreated youth with PTSD. Volumetric results were not influenced by psychopathology or maltreatment variables. We identified volumetric differences in extinction-related structures between maltreated youth with PTSD from those without PTSD. Alterations of the vmPFC may be one mechanism that mediates the pathway from PTSD to comorbidity. Further longitudinal work is needed to determine neurobiological factors related to chronic and persistent PTSD, and to PTSD resilience despite maltreatment.
Hypertension is associated with cardiovascular events in adults. Subclinical changes to left ventricular strain and diastolic function have been found before development of decreased left ventricular ...ejection fraction and cardiovascular events. Our objective was to study effects of blood pressure (BP) on ventricular function in youth across the BP spectrum. Vital signs and labs were obtained in 346 participants aged 11 to 19 years who had BP categorized as low-risk (N=144; systolic BP <75th percentile), mid-risk (N=83; systolic BP ≥80th and <90th percentile), and high-risk (N=119; systolic BP ≥90th percentile). Echocardiography was performed to assess left ventricular strain and diastolic function. Differences between groups were analyzed by ANOVA. General linear models were constructed to determine independent predictors of systolic and diastolic function. Mid-risk and high-risk participants had greater adiposity and more adverse metabolic labs (lower HDL high-density lipoprotein, higher glucose, and higher insulin) than the low-risk group. Mid-risk and high-risk participants had significantly lower left ventricular ejection fraction and peak global longitudinal strain than the low-risk group (both P≤0.05). The E/e′ ratio was higher in the high-risk group versus the low-risk and mid-risk groups, and the e′/a′ ratio was lower in the high-risk versus the low-risk group (both P≤0.05). BP and adiposity were statistically significant determinants of left ventricular systolic and diastolic function. Subclinical changes in left ventricular systolic and diastolic function can be detected even at BP levels below the hypertensive range as currently defined.
For children and young adults, living with chronic kidney disease (CKD) poses physical, mental, and social challenges. The mental health functioning of children and adolescents with CKD plays an ...important role in the medical, educational, vocational, and quality of life outcomes, yet receives little systematic attention in the busy pediatric nephrology clinic. This article will provide an overview of the prevalence of mental illness and symptoms in children and young adults with CKD, strategies to assess for dysfunction, and the long-term outcomes associated with impaired functioning. While there is a relative dearth of literature regarding evidence-based interventions in this population to improve mental health functioning, we provide “best practice” strategies based on the available literature to address emotional and/or behavioral challenges once they are identified. More research is needed to define appropriate interventions to alleviate mental health issues and social-emotional distress, and this review of the literature will serve to provide directions for future research.
Hypertension-related increased arterial stiffness predicts development of target organ damage (TOD) and cardiovascular disease. We hypothesized that blood pressure (BP)-related increased arterial ...stiffness is present in youth with elevated BP and is associated with TOD.
Participants were stratified by systolic BP into low- (systolic BP <75th percentile, n=155), mid- (systolic BP ≥80th and <90th percentile, n=88), and high-risk BP categories (≥90th percentile, n=139), based on age-, sex- and height-specific pediatric BP cut points. Clinic BP, 24-hour ambulatory BP monitoring, anthropometrics, and laboratory data were obtained. Arterial stiffness measures included carotid-femoral pulse wave velocity and aortic stiffness. Left ventricular mass index, left ventricular systolic and diastolic function, and urine albumin/creatinine were collected. ANOVA with Bonferroni correction was used to evaluate differences in cardiovascular risk factors, pulse wave velocity, and cardiac function across groups. General linear models were used to examine factors associated with arterial stiffness and to determine whether arterial stiffness is associated with TOD after accounting for BP.
Pulse wave velocity increased across groups. Aortic distensibility, distensibility coefficient, and compliance were greater in low than in the mid or high group. Significant determinants of arterial stiffness were sex, age, adiposity, BP, and LDL (low-density lipoprotein) cholesterol. Pulse wave velocity and aortic compliance were significantly associated with TOD (systolic and diastolic cardiac function and urine albumin/creatinine ratio) after controlling for BP.
Higher arterial stiffness is associated with elevated BP and TOD in youth emphasizing the need for primary prevention of cardiovascular disease.
Hypertension is associated with left ventricular hypertrophy (LVH), a risk factor for cardiovascular events. Since cardiovascular events in youth are rare, hypertension has historically been defined ...by the 95th percentile of the normal blood pressure (BP) distribution in healthy children. The optimal BP percentile associated with LVH in youth is unknown. We aimed to determine the association of systolic BP (SBP) percentile, independent of obesity, on left ventricular mass index (LVMI), and to estimate which SBP percentile best predicts LVH in youth. We evaluated SBP, anthropometrics, and echocardiogram in 303 adolescents (mean age 15.6 years, 63% white, 55% male) classified by SBP as low-risk (L=141, <80th percentile), mid-risk (M=71, 80–<90th percentile), or high-risk (H=91, ≥90th percentile) using the mean of 6 measurements at 2 visits according to the 2017 guidelines. Logistic regression was used to determine the sensitivity and specificity of various SBP percentiles associated with LVH. ResultsBP groups did not differ by age or demographics but differed slightly by body mass index. Mean BP, LVMI, and prevalence of LVH increased across groups (BPL=111/75, M=125/82, and H=133/92 mm Hg; LVMIL=31.2, M=34.2, and H=34.9 g/m; LVHL=13%, M=21%, H=27%, all P<0.03). SBP percentile remained a significant determinant of LVMI after adjusting for covariates. The 90th percentile for SBP resulted in the best balance between sensitivity and specificity for predicting LVH (LVMI≥38.6 g/m). Abnormalities in cardiac structure in youth can be found at BP levels below those used to define hypertension.
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: β = 0.053, P = 0.02; visual spatial: β = 0.062, P = 0.02; and visual working memory: β = 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.
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