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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 Although hypertension is known to have an adverse impact on health-related quality of life (HRQoL) in adults, little is known about the effects of hypertension and use of antihypertensive medications on HRQoL in hypertensive children with chronic kidney disease (CKD). Methods Cross-sectional and longitudinal assessment of impact of elevated blood pressure (BP) and antihypertensive medication use on HRQoL scores obtained in children enrolled in the Chronic Kidney Disease in Children (CKiD) Study. Blood pressure was measured both manually and by ambulatory blood pressure monitoring. HRQoL was assessed with the PedsQL survey. Results The study sample included 551 participants with sufficient data for cross-sectional and longitudinal analyses. Cross-sectional analysis of presence of prehypertension or hypertension and impact on HRQoL found mild associations between elevated BP and HRQoL scores with overall PedsQL parent and child scores averaging 79 vs. 76.5 and 83 vs. 78.5, respectively. However, no associations persisted under longitudinal multivariate analysis. Conclusions Despite apparent small effects of elevated BP on HRQoL at baseline, no association was found between the presence of elevated BP and HRQoL over time in children with mild-to-moderate CKD. In addition, antihypertensive medication use did not appear to have an impact on HRQoL in this population., Author(s): Cynthia Wong[sup.1] , Arlene Gerson[sup.2] , Stephen R. Hooper[sup.3] , Matthew Matheson[sup.4] , Marc Lande[sup.5] , Juan Kupferman[sup.6] , Susan Furth[sup.7] , Bradley Warady[sup.8] , Joseph Flynn[sup.9] , For [...]

Background Children with chronic kidney disease (CKD) may have impaired caloric intake through a variety of mechanisms, with decreased appetite as a putative contributor. In adult CKD, decreased appetite has been associated with poor clinical outcomes. There is limited information about this relationship in pediatric CKD. Methods A total of 879 participants of the Chronic Kidney Disease in Children (CKiD) study were studied. Self-reported appetite was assessed annually and categorized as very good, good, fair, or poor/very poor. The relationship between appetite and iohexol or estimated glomerular filtration rate (ieGFR), annual changes in anthropometrics z-scores, hospitalizations, emergency room visits, and quality of life were assessed. Results An ieGFR 90. Appetite did not predict changes in height, weight, or BMI z-scores. Patients not reporting a very good appetite had more hospitalizations over the next year than those with a very good appetite. Worse appetite was significantly associated with lower parental and patient reported quality of life. Conclusions Self-reported appetite in children with CKD worsens with lower ieGFR and is correlated with clinical outcomes, including hospitalizations and quality of life., Author(s): Frank W. Ayestaran[sup.1] [sup.2] , Michael F. Schneider[sup.3] , Frederick J. Kaskel[sup.4] , Poyyapakkam R. Srivaths[sup.5] , Patricia W. Seo-Mayer[sup.6] , Marva Moxey-Mims[sup.7] , Susan L. Furth[sup.8] [sup.9] , [...]

Background Self-reported physical activity (PA) and screen time exposure in adolescents with chronic kidney disease (CKD) has not been evaluated. Methods We performed a cross-sectional analysis of PA and screen time in 224 adolescents at entry into the Chronic Kidney Disease in Children (CKiD) cohort. We compared proportions of CKiD vs. healthy 2012 National Health and Nutrition Examination Survey (NHANES) participants reporting the recommended 60 min of PA 7 days/week or [less than or equal to] 2 h/day of entertainment screen time (binomial probability test). Within CKiD, we assessed correlates of PA and screen time using multivariable logistic and linear regression and examined longitudinal data for 136 participants. Results Median age of CKiD participants was 15 years, and 60 % were male. Median estimated glomerular filtration rate (eGFR) was 41.3 (IQR 30.8, 52.3) ml/min/1.73 m.sup.2. Only 13 % of CKiD participants met recommendations for PA vs. 25 % of NHANES (p < 0.001), while 98 % in CKiD exceeded the recommended screen time vs. 73 % in NHANES (p < 0.001). Within CKiD, obesity (p = 0.04) and lower eGFR (p = 0.02) were independently associated with greater screen time. Conclusions Adolescents with CKD engage in significantly less PA and greater screen time than healthy youth in the United States, and this may worsen over time., Author(s): Stephanie L. Clark[sup.1] [sup.2] , Michelle R. Denburg[sup.1] [sup.2] , Susan L. Furth[sup.1] [sup.2] Author Affiliations: (1) Division of Nephrology, The Children's Hospital of Philadelphia, 34th Street and Civic [...]

BACKGROUND. There is frequent uncertainty in the identification of specific etiologies of chronic kidney disease (CKD) in children. Recent studies indicate that chromosomal microarrays can identify rare genomic imbalances that can clarify the etiology of neurodevelopmental and cardiac disorders in children; however, the contribution of unsuspected genomic imbalance to the incidence of pediatric CKD is unknown. METHODS. We performed chromosomal microarrays to detect genomic imbalances in children enrolled in the Chronic Kidney Disease in Children (CKiD) prospective cohort study, a longitudinal prospective multiethnic observational study of North American children with mild to moderate CKD. Patients with clinically detectable syndromic disease were excluded from evaluation. We compared 419 unrelated children enrolled in CKiD to multiethnic cohorts of 21,575 children and adults that had undergone microarray genotyping for studies unrelated to CKD. RESULTS. We identified diagnostic copy number disorders in 31 children with CKD (7.4% of the cohort). We detected 10 known pathogenic genomic disorders, including the 17q12 deletion HNF1 homeoboxB (HNF1B) and triple X syndromes in 19 of 419 unrelated CKiD cases as compared with 98 of 21,575 control individuals (OR 10.8, P = 6.1 x [10.sup.-20]). In an additional 12 CKiD cases, we identified 12 likely pathogenic genomic imbalances that would be considered reportable in a clinical setting. These genomic imbalances were evenly distributed among patients diagnosed with congenital and noncongenital forms of CKD. In the vast majority of these cases, the genomic lesion was unsuspected based on the clinical assessment and either reclassified the disease or provided information that might have triggered additional clinical care, such as evaluation for metabolic or neuropsychiatric disease. CONCLUSION. A substantial proportion of children with CKD have an unsuspected genomic imbalance, suggesting genomic disorders as a risk factor for common forms of pediatric nephropathy. Detection of pathogenic imbalances has practical implications for personalized diagnosis and health monitoring in this population. TRIAL REGISTRATION. ClinicalTrials.gov NCT00327860. FUNDING. This work was supported by the NIH, the National Institutes of Diabetes and Digestive and Kidney Diseases (NIDDK), the National Institute of Child Health and Human Development, and the National Heart, Lung, and Blood Institute., Introduction Chronic kidney disease (CKD) is a major public health problem that affects up to 13% of the United States population (1-3). The impact of CKD in children is particularly [...]

Background Hepcidin, a key iron regulatory protein, is elevated in patients with chronic kidney disease (CKD). Its role in the development and progression of the anemia of CKD in children remains poorly defined. Methods Cross-sectional and longitudinal study in children aged 1-16 years with stage 2-4 CKD in the Chronic Kidney Disease in Children (CKiD) cohort (n=133) with hepcidin measured at baseline and hemoglobin (HGB) measured annually at follow-up. Anemia was defined as HGB Results Hepcidin levels correlated negatively with glomerular filtration rate (GFR; r=-0.22, p=0.01) and positively with ferritin (r=0.67, p Conclusions Higher hepcidin levels are associated with a decreased HGB and an increased risk of incident anemia, and this association is most significant among subjects with lower GFR. Keywords Chronic kidney disease * Children * Anemia * Hepcidin, Introduction The identification of hepcidin as a key iron-regulatory protein has helped to clarify the mechanisms underlying the anemia of chronic kidney disease (CKD), beyond erythropoietin deficiency alone. Hepcidin, encoded [...]

At a recent meeting of international experts on clinical aspects of progressive chronic kidney disease (CKD), an extensive analysis of extant clinical trials was used to develop more effective and economical surrogate markers for CKD outcomes in adults. This article describes the reasons for this undertaking, the methods and conclusions of the meeting, and the relevance of these findings to pediatric nephrology. Keywords Surrogate markers * Chronic kidney disease * Kidney function * GFR * Pediatric CKD * Locusta migratoria, Introduction On December 2-4, 2012, a meeting was held in Baltimore, Maryland, USA, to discuss the utility of glomerular filtration rate (GFR) decline as an endpoint for clinical trials of [...]

Background: Young age has been associated with poorer control of hypertension in children with chronic kidney disease (CKD). Using data from the CKiD Study (Chronic Kidney Disease in Children), we examined the relationship between age, hypertensive blood pressure (BP) recognition, and pharmacologic BP control in children with nondialysis-dependent CKD. Methods: Participants included 902 CKiD Study participants with CKD stages 2 to 4. A total of 3550 annual study visits met inclusion criteria and participants were stratified by age (0 to <7, ≥7 to <13, ≥13 to ≤18 years). Generalized estimating equations to account for repeated measures were applied to logistic regression analyses to evaluate the association of age with unrecognized hypertensive BP and medication use. Results: Children <7 years of age had a higher prevalence of hypertensive BP and a lower prevalence of antihypertensive medication use compared with older children. At visits where participants <7 years of age had hypertensive BP readings, 46% had unrecognized, untreated hypertensive BP compared with 21% of visits for children ≥13 years of age. The youngest age group was associated with higher odds of unrecognized hypertensive BP (adjusted odds ratio, 2.11 [95% CI, 1.37–3.24]) and lower odds of antihypertensive medication use among those with unrecognized hypertensive BP (adjusted OR, 0.51 [95% CI, 0.27–0.996]). Conclusions: Children younger than 7 years of age with CKD are more likely to have both undiagnosed and undertreated hypertensive BP. Efforts to improve BP control in young children with CKD are needed to minimize development of cardiovascular disease and slow CKD progression. [ABSTRACT FROM AUTHOR]

Background: Obesity is prevalent among children with chronic kidney disease (CKD) and is associated with cardiovascular disease and reduced quality of life. Its relationship with pediatric CKD progression has not been described. Methods: We evaluated relationships between both body mass index (BMI) category (normal, overweight, obese) and BMI z-score (BMIz) change on CKD progression among participants of the Chronic Kidney Disease in Children study. Kaplan–Meier survival curves and multivariable parametric failure time models depict the association of baseline BMI category on time to kidney replacement therapy (KRT). Additionally, the annualized percentage change in estimated glomerular filtration rate (eGFR) was modeled against concurrent change in BMIz using multivariable linear regression with generalized estimating equations which allowed for quantification of the effect of BMIz change on annualized eGFR change. Results: Participants had median age of 10.9 years [IQR: 6.5, 14.6], median eGFR of 50 ml/1.73 m2 [IQR: 37, 64] and 63% were male. 160 (27%) of 600 children with non-glomerular and 77 (31%) of 247 children with glomerular CKD progressed to KRT over a median of 5 years [IQR: 2, 8]. Times to KRT were not significantly associated with baseline BMI category. Children with non-glomerular CKD who were obese experienced significant improvement in eGFR (+ 0.62%; 95% CI: + 0.17%, + 1.08%) for every 0.1 standard deviation concurrent decrease in BMI. In participants with glomerular CKD who were obese, BMIz change was not significantly associated with annualized eGFR change. Conclusion: Obesity may represent a target of intervention to improve kidney function in children with non-glomerular CKD. A higher resolution version of the Graphical abstract is available as Supplementary information [ABSTRACT FROM AUTHOR]

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 [...]