Mental health and social-emotional functioning in children and adolescents with chronic kidney disease.

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.

Associations of body mass index (BMI) and BMI change with progression of chronic kidney disease in children.

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.

Vitamin D supplementation in children and young adults with persistent proteinuria secondary to glomerular disease.

BACKGROUND: Vitamin D deficiency is common in glomerular disease. Supplementation may be ineffective due to ongoing urinary losses of vitamin D binding protein. We sought to determine if daily cholecalciferol supplementation would increase vitamin D concentrations in children with glomerular disease and persistent proteinuria, without adverse effects. METHODS: Eighteen participants at least 5 years of age with primary glomerular disease and urine protein:creatinine ratio ≥ 0.5 were enrolled from four pediatric nephrology practices to receive cholecalciferol supplementation: 4,000 IU or 2,000 IU per day for serum 25 hydroxyvitamin vitamin D (25OHD) concentrations < 20 ng/mL and 20 ng/mL to < 30 ng/mL, respectively. Measures of vitamin D and mineral metabolism were obtained at baseline and weeks 6 and 12. Multivariable generalized estimating equation (GEE) regression estimated mean percent changes in serum 25OHD concentration. RESULTS: Median baseline 25OHD was 12.8 ng/mL (IQR 9.3, 18.9) and increased to 27.8 ng/mL (20.5, 36.0) at week 6 (p < 0.001) without further significant increase at week 12. A total of 31% of participants had a level ≥ 30 ng/mL at week 12. Supplementation was stopped in two participants at week 6 for mildly elevated calcium and phosphorus, respectively, with subsequent declines in 25OHD of > 20 ng/mL. In the adjusted GEE model, 25OHD was 102% (95% CI: 64, 141) and 96% (95% CI: 51, 140) higher versus baseline at weeks 6 and 12, respectively (p < 0.001). CONCLUSION: Cholecalciferol supplementation in vitamin D deficient children with glomerular disease and persistent proteinuria safely increases 25OHD concentration. Ideal dosing to fully replete 25OHD concentrations in this population remains unknown. CLINICAL TRIAL: NCT01835639. A higher resolution version of the Graphical abstract is available as Supplementary information.

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.

A review of ferric citrate clinical studies, and the rationale and design of the Ferric Citrate and Chronic Kidney Disease in Children (FIT4KiD) trial.

Pediatric chronic kidney disease (CKD) is characterized by many co-morbidities, including impaired growth and development, CKD-mineral and bone disorder, anemia, dysregulated iron metabolism, and cardiovascular disease. In pediatric CKD cohorts, higher circulating concentrations of fibroblast growth factor 23 (FGF23) are associated with some of these adverse clinical outcomes, including CKD progression and left ventricular hypertrophy. It is hypothesized that lowering FGF23 levels will reduce the risk of these events and improve clinical outcomes. Reducing FGF23 levels in CKD may be accomplished by targeting two key stimuli of FGF23 production-dietary phosphate absorption and iron deficiency. Ferric citrate is approved for use as an enteral phosphate binder and iron replacement product in adults with CKD. Clinical trials in adult CKD cohorts have also demonstrated that ferric citrate decreases circulating FGF23 concentrations. This review outlines the possible deleterious effects of excess FGF23 in CKD, summarizes data from the adult CKD clinical trials of ferric citrate, and presents the Ferric Citrate and Chronic Kidney Disease in Children (FIT4KiD) study, a randomized, placebo-controlled trial to evaluate the effects of ferric citrate on FGF23 in pediatric patients with CKD stages 3-4 (ClinicalTrials.gov Identifier NCT04741646).

Longitudinal outcomes of body mass index in overweight and obese children with chronic kidney disease.

BACKGROUND: Longitudinal changes in body mass index (BMI) among overweight and obese children with chronic kidney disease (CKD) are not well characterized. We studied longitudinal trajectories and correlates of these trajectories, as results may identify opportunities to optimize health outcomes. METHODS: Longitudinal changes in age-sex-specific BMI z-scores over 1851 person-years of follow-up were assessed in 524 participants of the Chronic Kidney Disease in Children Study. A total of 353 participants were categorized as normal (BMI > 5th to < 85th percentile), 56 overweight (BMI ≥ 85th to 95th percentile) and 115 obese (BMI ≥ 95th percentile) based on the average of three BMI measurements during the first year of follow-up. Studied covariates included age, sex, race, CKD etiology, corticosteroid usage, household income, and maternal education. RESULTS: In unadjusted analysis, BMI z-scores decreased over time in elevated BMI groups (overweight: mean = - 0.06 standard deviations (SD) per year, 95% CI: - 0.11, - 0.01; obese: mean = - 0.04 SD per year, 95% CI: - 0.07, - 0.01). Among obese children, only age was associated with change in BMI z-score; children < 6 years had a mean decrease of 0.19 SD during follow-up (95% CI: - 0.30, - 0.09). Socioeconomic factors were not associated with change in BMI. CONCLUSION: Overweight and obese children with CKD demonstrated a significant annual decline in BMI, though the absolute change was modest. Among obese children, only age < 6 years was associated with significant decline in BMI. Persistence of elevated BMI in older children and adolescents with CKD underscores the need for early prevention and effective intervention.

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.

Grip strength in children with chronic kidney disease.

BACKGROUND: The relationship between muscle strength and chronic kidney disease (CKD) in children is unknown. This study aims to quantify the association between grip strength (GS) and kidney function and to explore factors associated with grip strength in children and adolescents with CKD. METHODS: We included 411 children (699 GS assessments) of the Chronic Kidney Disease in Children (CKiD) study. They were matched by age, sex, and height to a healthy control from the National Health and Nutrition Examination Survey to quantify the relationship between GS and CKD. Linear mixed models were used to identify factors associated with GS among CKD patients. RESULTS: Median GS z-score was - 0.72 (IQR - 1.39, 0.11) among CKD patients with CKD stages 2 through 5 having significantly lower GS than CKD stage 1. Compared with healthy controls, CKiD participants had a decreased GS z-score (- 0.53 SD lower, 95% CI - 0.67 to - 0.39) independent of race/ethnicity and body mass index. Factors associated with reduced GS included longer duration of CKD, pre-pubertal status, delayed puberty, neuropsychiatric comorbidities, need of feeding support, need for alkali therapy, and hemoglobin level. Decreased GS was also associated with both a lower frequency and intensity of physical activity. CONCLUSIONS: CKD is associated with impaired muscle strength in children independent of growth retardation and BMI. Exposure to CKD for a prolonged time is associated with impaired muscle strength. Potential mediators of the impact of CKD on muscle strength include growth retardation, acidosis, poor nutritional status, and low physical activity. Additional studies are needed to assess the efficacy of interventions targeted at these risk factors.

Health-related quality of life in glomerular disease.

There is scant literature describing the effect of glomerular disease on health-related quality of life (HRQOL). The Cure Glomerulonephropathy study (CureGN) is an international longitudinal cohort study of children and adults with four primary glomerular diseases (minimal change disease, focal segmental glomerulosclerosis, membranous nephropathy, and IgA nephropathy). HRQOL is systematically assessed using items from the Patient-Reported Outcomes Measurement Informative System (PROMIS). We assessed the relationship between HRQOL and demographic and clinical variables in 478 children and 1115 adults at the time of enrollment into CureGN. Domains measured by PROMIS items included global assessments of health, mobility, anxiety, fatigue, and sleep impairment, as well as a derived composite measure incorporating all measured domains. Multivariable models were created that explained 7 to 32% of variance in HRQOL. Patient-reported edema consistently had the strongest and most robust association with each measured domain of HRQOL in multivariable analysis (adjusted ß [95% CI] for composite PROMIS score in children, -5.2 [-7.1 to -3.4]; for composite PROMIS score in adults, -6.1 [-7.4 to -4.9]). Female sex, weight (particularly obesity), and estimated glomerular filtration rate were also associated with some, but not all, domains of HRQOL. Primary diagnosis, disease duration, and exposure to immunosuppression were not associated with HRQOL after adjustment. Sensitivity analyses and interaction testing demonstrated no significant association between disease duration or immunosuppression and any measured domain of HRQOL. Thus, patient-reported edema has a consistent negative association with HRQOL in patients with primary glomerular diseases, with substantially greater impact than other demographic and clinical variables.

Ethical and Policy Considerations for Genomic Testing in Pediatric Research: The Path Toward Disclosing Individual Research Results.

DNA is now commonly collected in clinical research either for immediate genomic analyses or stored for future studies. Many genomic studies were previously designed without awareness of the ethical issues that might arise regarding the disclosure of genomic test results. At the start of the Chronic Kidney Disease in Children (CKiD) Cohort Study in 2004, we did not foresee the advent of genomic technology or the associated ethical issues pertaining to genetic research in children. Recent genomic studies and ancillary proposals using genomic technology stimulated the CKiD investigators to reassess the current ethical and policy environment pertaining to genomic testing and results disclosure. We consider the issues pertaining to next generation sequencing and individual results disclosure that may guide current and future research practices.

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.

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.

Clinical Indices Can Standardize and Monitor Pediatric Care: A Novel Mechanism to Improve Quality and Safety.

OBJECTIVE: The Cancer Care Index (CCI), a single metric that sums the number of undesirable patient events in a given time frame (either preventable harm events or missed opportunities to provide optimal care), resulted in a 42% improvement in performance. Our objective was to test the index concept in other service lines to determine whether similar performance improvement occurred. STUDY DESIGN: Care indices were developed and introduced in 3 additional service lines: Nephrology (Chronic Kidney Disease Care Index; CKDCI), Pulmonology (Lung Transplantation Care Index; LTCI), and Otolaryngology (Tracheostomy Care Index; TCI). After reaching agreement on specific harms to be avoided and elements of optimal care that should be reliably delivered, these items were compiled into indices that were updated monthly. Reports included each element individually and the total for all elements. Baseline performance was calculated retrospectively for the previous year. RESULTS: Significant improvement in performance occurred in each program following implementation of the clinical indices. The CKDCI was decreased by 63.2% (P < .001), the LTCI was decreased by 89.5% (P < .001), and the TCI was decreased by 53.0% (P < .001). Surveyed staff indicated satisfaction with use of the metric. CONCLUSIONS: Clinical indices are useful for evaluating and managing the overall reliability of a program's ability to deliver optimal care, and are associated with improved clinical performance and satisfaction by service line staff when incorporated into a program's operation.

Genomic Disorders and Neurocognitive Impairment in Pediatric CKD.

Children with CKD are at increased risk for neurocognitive impairment, but whether neurocognitive dysfunction is solely attributable to impaired renal function is unclear. Data from the CKD in Children Study Chronic Kidney Disease in Children (CKiD) Study indicate that a subset of children with CKD have unsuspected genomic disorders that predispose them to organ malformations and neurocognitive impairment. We therefore tested whether the CKiD Study participants with genomic disorders had impaired neurocognitive performance at enrollment. Compared with noncarriers (n=389), children with genomic disorders (n=31) scored significantly poorer on all measures of intelligence, anxiety/depressive symptoms, and executive function (differences of 0.6-0.7 SD; P=1.2×10-3-2.4×10-4). These differences persisted after controlling for known modifiers, including low birth weight, maternal education, seizure disorder, kidney disease duration, and genetically defined ancestry. The deleterious effect of genomic disorders on neurocognitive function was significantly attenuated in offspring of mothers with higher education, indicating the potential for modification by genetic and/or environmental factors. These data indicate that impaired neurocognitive function in some children with CKD may be attributable to genetic lesions that affect both kidney and neurocognitive development. Early identification of genomic disorders may provide opportunity for early diagnosis and personalized interventions to mitigate the effect on neurocognitive function.

Cognitive Function in Children with Lupus Nephritis: A Cross-Sectional Comparison with Children with Other Glomerular Chronic Kidney Diseases.

OBJECTIVE: To identify factors contributing to cognitive impairment in children with lupus nephritis. STUDY DESIGN: A cross-sectional analysis of a large multicenter national cohort of children with chronic kidney disease (CKD) using standardized measures to determine baseline neuropsychiatric function and health-related quality of life (HRQoL) in children with lupus nephritis (n = 34), and to compare baseline function with that in children with other forms of glomerular CKD (gCKD; n = 171). We used inverse probability weighting via a logistic model for propensity score analysis to achieve balance between children with lupus nephritis and those with other glomerular causes of CKD, adjusting for known confounders. We used linear regression models to compare neurocognitive outcomes between exposure groups, adjusting for current prednisone use and testing for an interaction between current prednisone use and lupus nephritis, and to test for an association between cognitive function and HRQoL. RESULTS: Current prednisone use was independently associated with worse attention (P < .01) and better adaptive skills (P = .04), and there was a significant interaction between current prednisone use and lupus nephritis for internalizing problems, with worse parent-reported internalizing problems in children with lupus nephritis on prednisone (P = .047). Better parent-reported HRQoL was associated with better visual memory (P = .01), and better child-reported HRQoL was associated with better attention (P < .01) and inhibitory control (P < .01). Both parent and child HRQoL were associated with better measures of executive function (P = .02 and < .001, respectively). CONCLUSION: Children with lupus nephritis have comparable or better cognitive function than their peers with other gCKDs, which is reassuring given the multiorgan and lifelong complications associated with lupus.

Approach to growth hormone therapy in children with chronic kidney disease varies across North America: the Midwest Pediatric Nephrology Consortium report.

BACKGROUND: Growth impairment remains common in children with chronic kidney disease (CKD). Available literature indicates low level of recombinant human growth hormone (rhGH) utilization in short children with CKD. Despite efforts at consensus guidelines, lack of high-level evidence continues to complicate rhGH therapy decision-making and the level of practice variability in rhGH treatment by pediatric nephrologists is unknown. METHODS: Cross-sectional online survey electronically distributed to pediatric nephrologists through the Midwest Pediatric Nephrology Consortium and American Society of Pediatric Nephrology. RESULTS: Seventy three pediatric nephrologists completed the survey. While the majority (52.1%) rarely involve endocrinology in rhGH management, 26.8% reported that endocrinology managed most aspects of rhGH treatment in their centers. The majority of centers (68.5%) have a dedicated renal dietitian, but 20.6% reported the nephrologist as the primary source of nutritional support for children with CKD. Children with growth failure did not receive rhGH most commonly because of family refusal. Differences in initial work-up for rhGH therapy include variable use of bone age (95%), thyroid function (58%), insulin-like growth factor-1 (40%), hip/knee X-ray (36%), and ophthalmologic evaluation (7%). Most pediatric nephrologists (95%) believe that rhGH treatment improves quality of life, but only 24% believe that it improves physical function; 44% indicated that rhGH improves lean body mass. CONCLUSIONS: There is substantial variation in pediatric nephrology practice in addressing short stature and rhGH utilization in children with CKD. Hence, there may be opportunities to standardize care to study and improve growth outcomes in short children with CKD.

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.