Chronic Kidney Disease In Children Study Research Articles

Assessing bias in GFR estimating equations: improper GFR stratification can yield misleading results.

Assessing bias (estimated - measured) is key to evaluating glomerular filtration rate (GFR). Stratification by subgroups can indicate where equations perform differently. However, there is a fallacy in the assessment of two instruments (e.g., eGFR and mGFR) when stratifying on the level of only one of those instruments. Here, we present statistical aspects of the problem and a solution for GFR stratification along with an empirical investigation using data from the CKiD study. Compared and contrasted biases (eGFR relative to mGFR) with 95% confidence intervals within strata of mGFR only, eGFR only, and the average of mGFR and eGFR using data from the Chronic Kidney Disease in Children (CKiD) study. A total of 304 participants contributed 843 GFR studies with a mean mGFR of 48.46 (SD = 22.72) and mean eGFR of 48.67 (SD = 22.32) and correlation of 0.904. Despite strong agreement, eGFR significantly overestimated mGFR when mGFR < 30 (+ 6.2%; 95%CI + 2.9%, + 9.7%) and significantly underestimated when mGFR > 90 (-12.2%; 95%CI - 17.3%, - 7.0%). Significant biases in opposite direction were present when stratifying by eGFR only. In contrast, when stratifying by the average of eGFR and mGFR, biases were not significant (+ 1.3% and - 1.0%, respectively) congruent with strong agreement. Stratifying by either mGFR or eGFR only to assess eGFR biases is ubiquitous but can lead to inappropriate inference due to intrinsic statistical issues that we characterize and empirically illustrate using data from the CKiD study. Using the average of eGFR and mGFR is recommended for valid inferences in evaluations of eGFR biases.

Associations between anemia and FGF23 in the CKiD study

BackgroundFibroblast growth factor 23 (FGF23) is a bone-derived hormone that plays a central role in chronic kidney disease-mineral bone disorder and is associated with CKD progression and cardiovascular morbidity. Factors related to CKD-associated anemia, including iron deficiency, can increase FGF23 production. This study aimed to assess whether anemia and/or iron deficiency are associated with increased circulating concentrations of FGF23 in the large, well-characterized Chronic Kidney Disease in Children (CKiD) study cohort.MethodsHemoglobin concentrations, iron parameters, C-terminal (total) FGF23, intact FGF23, and relevant covariables were measured in cross-sectional analysis of CKiD study subjects.ResultsIn 493 pediatric patients with CKD (median [interquartile range] age 13 [9, 16] years), the median estimated glomerular filtration rate was 48 [35, 61] ml/min/1.73 m2, and 103 patients (21%) were anemic. Anemic subjects had higher total FGF23 concentrations than non-anemic subjects (204 [124, 390] vs. 109 [77, 168] RU/ml, p < 0.001). In multivariable linear regression modeling, anemia was independently associated with higher total FGF23, after adjustment for demographic, kidney-related, mineral metabolism, and inflammatory covariables (standardized β (95% confidence interval) 0.10 (0.04, 0.17), p = 0.002). In the subset of subjects with available iron parameters (n = 191), iron deficiency was not associated with significantly higher total FGF23 concentrations. In the subgroup that had measurements of both total and intact FGF23 (n = 185), in fully adjusted models, anemia was significantly associated with higher total FGF23 (standardized β (95% CI) 0.16 (0.04, 0.27), p = 0.008) but not intact FGF23 (standardized β (95% CI) 0.02 (−0.12, 0.15), p = 0.81).ConclusionsIn this cohort of pediatric patients with CKD, anemia was associated with increased total FGF23 levels but was not independently associated with elevated intact FGF23, suggesting possible effects on both FGF23 production and cleavage. Further studies are warranted to investigate non-mineral factors affecting FGF23 production and metabolism in CKD.Graphical abstractA higher resolution version of the Graphical abstract is available as Supplementary information

The Impact of Pediatric CKD on Educational and Employment Outcomes.

Pediatric patients with chronic kidney disease (CKD) are at risk for neurocognitive deficits and academic underachievement. This population may be at risk for lower educational attainment and higher rates of unemployment; however, published data has focused on patients with advanced CKD and exist in isolation from assessment of neurocognition and kidney function. Data from the Chronic Kidney Disease in Children (CKiD) cohort study were used to characterize educational attainment and employment status in young adults with CKD. We utilized ratings of executive function as a predictor of future educational attainment and employment status. Linear regression models predicted the highest grade level completed. Logistic regression models predicted unemployment. 296 CKiD participants aged 18 years or older had available educational data. 220/296 had employment data. By age 22, 97% had completed high school and 48% completed 2+ years of college. Among those reporting employment status, 58% were part- or full-time employed, 22% were non-working students, and 20% were unemployed and/or receiving disability. In adjusted models, lower kidney function (p=0.02), worse executive function (p=0.02), and poor performance on achievement testing (p=0.004) predicted lower grade level completed relative to expectation for age. CKiD study patients appear to have a better high school graduation rates (97%) than the adjusted national high school graduation rate (86%). Conversely, roughly 20% of participants were unemployed or receiving disability at study follow-up. Tailored interventions may benefit CKD patients with lower kidneyfunction and/or executive function deficits to optimize educational/employment outcomes in adulthood.

Nocturnal Dipping and Kidney Function Decline: Findings From the CKD in Children Study

IntroductionNormally, blood pressure (BP) declines by at least 10% from daytime to nighttime. In adults, blunted nocturnal dipping has been associated with more rapid decline in kidney function. Nondipping is prevalent in children with chronic kidney disease (CKD). We sought to determine whether nondipping is associated with proteinuria and progression to kidney failure in children with CKD. MethodsIn the prospective CKD in children (CKiD) cohort, Cox proportional hazards models were used to evaluate the relationship between baseline nondipping and progression to kidney failure. Linear mixed effects models were used to evaluate the relationship between nondipping and changes in iohexol glomerular filtration rate (GFR) and urine protein-to-creatinine ratio (log-UPCR, mg/mg) over time. ResultsAmong 620 participants, mean age was 11 (± 4) years, mean iohexol GFR was 52 (± 22) ml/min per 1.73 m2, and 40% were nondippers at baseline. There were 169 kidney failure events during 2.9 years (median) of follow-up. Dipping status was not significantly associated with kidney failure overall (hazard ratio [HR] 1.08; 95% confidence interval [CI] 0.77, 1.51) or in those with (HR 1.21; 95% CI 0.53, 2.77) or without (HR 1.05; 95% CI 0.71, 1.55) glomerular disease. Dipping status did not modify the relationship between time and change in iohexol GFR or log (UPCR) from baseline (interaction P values = 0.20 and 0.054, respectively). ConclusionNondipping is not associated with end-stage kidney disease, GFR decline, or change in proteinuria within the CKiD cohort.

Racial-ethnic diversity in ambulatory blood pressure monitoring in children with chronic kidney disease

BackgroundBlack adults with chronic kidney disease (CKD) have higher rates of hypertension as compared to White adults with CKD. Little is known of how race and ethnicity associate with the prevalence of hypertension in pediatric CKD patients. The aim was to compare ambulatory blood pressure monitoring (ABPM) results for patients with CKD enrolled in the Chronic Kidney Disease in Children (CKiD) study across racial-ethnic groups.MethodsPatients from the CKiD study who identified as non-Hispanic White, non-Hispanic Black, or Hispanic were included to analyze differences in ABPM results across these racial-ethnic groups. The outcomes were fitted using 3 progressively adjusted models.ResultsThis study included 501 CKiD participants with at least one successful ABPM study. Compared to White participants, Black participants had 4.2 mmHg higher mean sleep systolic blood pressure and 2.7 mmHg higher mean sleep diastolic blood pressure (p = 0.001 and p = 0.004, respectively). Additionally, Black participants had higher odds of abnormal wake systolic load (OR 1.88, 1.21–2.91, p = 0.005), wake diastolic load (OR 1.68, 1.03–2.73, p = 0.04), sleep systolic load (OR 2.19, 1.36–3.5, p = 0.001), sleep diastolic load (OR 2.01, 1.28–3.15, p = 0.002), systolic non-dipping (OR 2.02, 1.31–3.10, p = 0.001), and diastolic non-dipping (OR 2.69, 1.60–4.51, p < 0.001). Compared to White participants, Hispanic participants demonstrated only a lower sleep diastolic load (OR 0.54, 0.31–0.95, p = 0.03).ConclusionsBlack children with CKD have higher absolute nocturnal blood pressures and higher rates of abnormal dipping. Further studies are needed to determine the etiology of these differences and the clinical implications of racial-ethnic differences in ABPM outcomes within the pediatric CKD population.Graphical abstractA higher resolution version of the Graphical abstract is available as Supplementary information

Psychiatric Diagnoses in Children With CKD Compared to the General Population

Rationale & ObjectiveChildren with chronic kidney disease (CKD) are subject to physical and psychosocial challenges, which may confer greater risk of developing psychiatric disorders. We sought to examine key psychiatric diagnoses in children with CKD compared with those in the general pediatric population and assess the correlation between parent-reported diagnosis and self-reported symptoms of depression.Study DesignCross-sectional.Setting & ParticipantsChildren ages 2-17 years receiving current medical care who participated in the Chronic Kidney Disease in Children Study (CKiD) or the National Survey of Children’s Health.ExposureCKD.OutcomesParent-reported diagnoses of depression, anxiety, or attention-deficit and hyperactivity disorder (ADHD).Analytical ApproachUsing Poisson regression, we determined the age, sex, and race-adjusted prevalence ratio comparing diagnoses between children with CKD and those in the general population overall and within subgroups of sex, race, maternal education status, and CKD stage. Secondarily, we examined the correlation between depression status using standardized self-reported screening instrument scores and parent-reported diagnosis.ResultsEight hundred seventy-five children with CKD and 72,699 children in the general population were included. Those with CKD had an adjusted prevalence ratio of 1.32 (95% CI, 1.01-1.73) for depression, 0.72 (95% CI, 0.52-0.99) for anxiety, and 1.03 (95% CI, 0.86-1.25) for ADHD. The results were similar across subgroups of CKD stage, sex, race, or maternal education. The correlation between parent-reported diagnosis and instrument-detected depression was weak, r = 0.13 (95% CI, 0.03-0.23).LimitationsRetrospective parent- or self-reported data were used.ConclusionsChildren with CKD had a higher prevalence of parent-reported depression, equivalent prevalence of attention-deficit and hyperactivity disorder, and lower prevalence of anxiety diagnoses compared to other children. These findings are inconsistent with results of prior studies and suggest that baseline assessments used in CKiD may have limited utility in describing psychiatric disorders among children with CKD. Improved mental health assessment approaches in pediatric nephrology are needed.

The link between executive function, socio-emotional functioning and health-related quality of life in children and adolescents with mild to moderate chronic kidney disease.

Children and adolescents with mild to moderate chronic kidney disease (CKD) are at high risk for mild but persistent impairment in executive functions, which have been associated with low health-related quality of life (HRQOL) among children and adolescents with chronic health conditions. However, no similar link has been established among children and adolescents with mild to moderate CKD. Given the essential role executive functions play in the development of adequate cognitive, emotional and social skills, it is essential to gain a clearer understating of the magnitude and attributes of executive functions and its link to HRQOL in order to inform appropriate medical and educational interventions for this patient population. The aim of this study is to examine the relationship between executive functions, socio-emotional functioning and HRQOL in children and adolescents with mild to moderate CKD. A cross-sectional design was used for this secondary data analysis of 199 children and adolescents (ages 6-17) with mild to moderate CKD from the United States and Canada who receive care at hospitals associated with the Chronic Kidney Disease in Children Study (CKiD). The presence of impairment in executive functions and socio-emotional functioning (internalizing problems) significantly predicted lower HRQOL after controlling for key covariates (i.e., maternal education, anaemia and hypertension). Further, internalizing problems partially mediated the relationship between executive functions and HRQOL such that impairment in executive functions predicted lower HRQOL directly and indirectly by contributing to higher internalizing problems, which further contributed to low HRQOL. This study underscores the importance of executive functions and socio-emotional functioning in the manifestation of HRQOL. Given that HRQOL is potentially compromised for many children and adolescents with mild to moderate CKD, it will be important for both clinicians and researchers to examine a range of factors, including executive functions and socio-emotional functioning, in order to optimize HRQOL.

Organophosphate pesticides and progression of chronic kidney disease among children: A prospective cohort study

BackgroundGrowing evidence suggests that exposure to environmental chemicals, such as pesticides, impacts renal function and chronic kidney disease (CKD). However, it is not clear if pesticides may affect CKD progression and no studies exist in children. ObjectivesThe objective of this study was to examine associations between serially measured urinary OP pesticide metabolites and clinical and laboratory measures of kidney function over time among children with CKD. MethodsThis study used data on 618 participants enrolled in the CKD in Children study (CKiD), a cohort study of pediatric CKD patients from the US and Canada. Children were followed over an average of 3.0 years (standard deviation (SD) = 1.6) between 2005 and 2015. In serially collected urine samples over time, six nonspecific dialkyl phosphate (DAP) metabolites of OP pesticides were measured. Biomarkers of tubular injury (kidney injury molecule-1 (KIM-1) and neutrophil gelatinase-associated lipocalin (NGAL)) and oxidant stress (8-hydroxy-2′-deoxyguanosine (8-OHdG) and F2-isoprostane) were determined in the same specimens. Estimated glomerular filtration rate (eGFR), proteinuria, and blood pressure were assessed annually. ResultsDAPs were associated with increased KIM-1 and 8-OHdG throughout follow-up. A standard deviation increase in ∑diethyl metabolites was associated with increases of 11.9% (95% Confidence Interval (CI): 4.8%, 19.4%) and 13.2% (95% CI: 9.3%, 17.2%) in KIM-1 and 8-OHdG over time, respectively. DAPs were associated with lower eGFR at baseline and higher eGFR over subsequent years. ConclusionsThese findings provide preliminary evidence suggesting that urinary DAP metabolites are associated with subclinical kidney injury among children with CKD, which may signal the potential for clinical events to manifest in the future. The results from this study are significant from both a clinical and public health perspective, given that OP pesticide exposure is a modifiable risk factor.

Social Determinants of Cardiovascular Health in African American Children With CKD: An Analysis of the Chronic Kidney Disease in Children (CKiD) Study

To identify differences in socioeconomic factors (SES) and subclinical cardiovascular disease (CVD) markers by race among Chronic Kidney Disease in Children (CKiD) participants and determine whether differences in CVD markers persist after adjusting for SES. Analysis of 3,103 visits with repeated measures from 628 children (497 White participants; 131 African American participants) enrolled in the CKiD study. Children with mild-moderate CKD with at least 1 cardiovascular (CV) parameter (ambulatory blood pressure, left ventricular mass index [LVMI], or lipid profile) measured. African American race. Ambulatory hypertension, LVMI, triglycerides, high-density lipoprotein cholesterol. Due to increased CV risks of glomerular disease, the analysis was stratified by CKD cause. Inverse probability weighting was used to adjust for SES (health insurance, household income, maternal education, food insecurity, abnormal birth history). Linear and logistic regression were used to evaluate association of race with CV markers. African American children were disproportionately affected by adverse SES. African Americans with nonglomerular CKD had more instances of ambulatory hypertension and higher LVMI but more favorable lipid profiles. After adjustment for SES, age, and sex, the magnitude of differences in these CV markers was attenuated but remained statistically significant. Only LVMI differed by race in the glomerular CKD group, despite adjustment for SES. Study design limits causal inference. African American children with CKD are disproportionately affected by socioeconomic disadvantages compared with White children. The degree to which CV markers differ by race is influenced by disease etiology. African Americans with nonglomerular CKD have increased LVMI, more ambulatory hypertension, and favorable lipid profile, but attenuation in magnitude after adjustment for SES was observed. African Americans with glomerular CKD had increased LVMI, which persisted after SES adjustment. As many social determinants of health were not captured, future research should examine effects of systemic racism on CV health in this population.

Development and Validation of a Modified Full Age Spectrum Creatinine-Based Equation to Estimate Glomerular Filtration Rate : A Cross-sectional Analysis of Pooled Data.

The Chronic Kidney Disease in Children Study (CKiD) equation for children and the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation for adults are recommended serum creatinine (SCr)-based calculations for estimating glomerular filtration rate (GFR). However, these equations, as well as their combination, have limitations, notably the problem of implausible changes in GFR during the transition from adolescence to adulthood and overestimation of GFR in young adults. The full age spectrum (FAS) equation addresses these issues but overestimates GFR when SCr levels are low. To develop and validate a modified FAS SCr-based equation combining design features of the FAS and CKD-EPI equations. Cross-sectional analysis with separate pooled data sets for development and validation. Research and clinical studies (n= 13) with measured GFR available. 11251 participants in 7 studies (development and internal validation data sets) and 8378 participants in 6 studies (external validation data set). Clearance of an exogenous marker (reference method), SCr level, age, sex, and height were used to develop a new equation to estimate GFR. The new European Kidney Function Consortium (EKFC) equation is a FAS equation with low bias (-1.2 mL/min/1.73 m2 [95% CI, -2.7 to 0.0 mL/min/1.73 m2] in children and -0.9 mL/min/1.73 m2 [CI, -1.2 to -0.5 mL/min/1.73 m2] in adults) across the FAS (2 to 90 years) and SCr range (40 to 490 µmol/L [0.45 to 5.54 mg/dL]) and with fewer estimation errors exceeding 30% (6.5% [CI, 3.8% to 9.1%] in children and 3.1% [CI, 2.5% to 3.6%] in adults) compared with the CKiD and CKD-EPI equations. No Black patients were included. The new EKFC equation shows improved accuracy and precision compared with commonly used equations for estimating GFR from SCr levels. Swedish Research Council (Vetenskapsrådet).

Association of pulse pressure, pulse pressure index, and ambulatory arterial stiffness index with kidney function in a cross-sectional pediatric chronic kidney disease cohort from the CKiD study.

The morbidity and mortality of adult and pediatric chronic kidney disease (CKD) and end-stage renal disease (ESRD) populations are mainly driven by cardiovascular disease (CVD). Improving CVD outcomes focuses on risk assessment of factors including diastolic blood pressure (DBP), systolic blood pressure (SBP), left ventricular mass index (LVMI), pulse pressure (PP), and pulse pressure index (PPi), which is calculated as PP/SBP. These markers are also proven predictors of CKD progression; however, their role in children has not been established. This study aims to evaluate the relationship between PP, PPi, ambulatory arterial stiffness index (AASI), and proteinuria with kidney function in pediatric CKD patients; it is a retrospective analysis of 620 patients (1-16years) from the NIDDK Chronic Kidney Disease in Children (CKiD) registry. The authors analyzed data for three separate cohorts: an overall CKD as well as immunological versus non-immunological cause for CKD groups. An inverse relationship was found between SBP, DBP, and PP with iGFR and LVMI in the overall CKD group. Our immunological CKD subgroup showed significantly higher serum creatinine, SBP, DBP, and PP values with significantly lower serum albumin levels compared to the non-immunological group. There were no significant differences with iohexol-based glomerular filtration rate (iGFR), LVMI, PPi, or high-sensitivity C-reactive protein (hs-CRP) between the two groups. A subgroup analysis demonstrated that SBP, DBP, and PP all correlated significantly with LVMI in the immunological CKD patients but not the non-immunological subgroup. Additionally, AASI data in the overall CKD population were significantly correlated with PP, PPi, and DBP. This study is one of the first to correlate noninvasive measurements of vascular compliance including PP, PPi, and AASI with iGFR and LVMI in a pediatric CKD cohort. Improving our understanding of surrogate markers for early CVD is integral to improving the care of pediatric CKD population as these patients have yet to develop the hard end points of ESRD, heart failure, myocardial infarction, or stroke.

A longitudinal analysis of the effect of anemia on health-related quality of life in children with mild-to-moderate chronic kidney disease.

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). 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 54ml/min/1.73m2. Thirty percent of children had anemia at index visit. Analysis of HRQOL scores revealed the presence of anemia was associated with significantly lower overall HRQOL (β = - 2.90 (95% CI = - 7.74, - 0.21), p = 0.04) and physical functioning (β = - 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 (β = - 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 (β = - 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. In children with CKD, anemia has an adverse effect on HRQOL which persists over time but does not appear to be progressive.

The CKiD study: overview and summary of findings related to kidney disease progression.

The Chronic Kidney Disease in Children (CKiD) cohort study is a North American (USA and Canada) multicenter, prospective study of children with chronic kidney disease (CKD). The original aims of the study were (1) to identify novel risk factors for CKD progression; (2) to measure the impact of kidney function decline on growth, cognition, and behavior; and (3) to characterize the evolution of cardiovascular disease risk factors. CKiD has developed into a national and international resource for the investigation of a variety of factors related to CKD in children. This review highlights notable findings in the area of CKD progression and outlines ongoing opportunities to enhance understanding of CKD progression in children. CKiD's contributions to the clinical care of children with CKD include updated and more accurate glomerular filtration rate estimating equations for children and young adults, and resources designed to help estimate the CKD progression timeline. In addition, results from CKiD have strengthened the evidence that treatment of hypertension and proteinuria should continue as a primary strategy for slowing the rate of disease progression in children.

Blood pressure in children with chronic kidney disease: lessons learned from the Chronic Kidney Disease in Children Cohort Study.

Cardiovascular disease (CVD) is common among children and adolescents with chronic kidney disease (CKD) and end-stage kidney disease (ESRD). However, the early accrual of CVD risk factors in children with CKD has not been well studied. The Chronic Kidney Disease in Children (CKiD) Study, a multicenter, prospective cohort study of children with mild-to-moderate CKD at study entry counts among its primary aims investigation of the drivers of CVD risk in this population. As the most prevalent CVD risk factor in children with CKD, blood pressure (BP) has been a major focus of investigation for the CKiD Study Group. Over the first 15years of the study, landmark publications have better defined the prevalence of hypertension, the frequency with which it is under-recognized and thus undertreated, and the consequences of elevated BP in this cohort. The purpose of this review is to summarize the contributions made by the CKiD Study in advancing knowledge of BP in this high-risk population, and to highlight areas in need of further study.

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.

Renal and Cardiovascular Morbidities Associated with APOL1 Status among African-American and Non-African-American Children with Focal Segmental Glomerulosclerosis.

African-American (AA) children with focal segmental glomerulosclerosis (FSGS) have later onset disease that progresses more rapidly than in non-AA children. It is unclear how APOL1 genotypes contribute to kidney disease risk, progression, and cardiovascular morbidity in children. We examined the prevalence of APOL1 genotypes and associated cardiovascular phenotypes among children with FSGS in the Chronic Kidney Disease in Children (CKiD) study; an ongoing multicenter prospective cohort study of children aged 1-16 years with mild to moderate kidney disease. A total of 140 AA children in the CKiD study were genotyped. High risk (HR) APOL1 genotypes were present in 24% of AA children (33/140) and were associated with FSGS, p < 0.001. FSGS was the most common cause of glomerular disease in children with HR APOL1 (89%; 25/28). Of 32 AA children with FSGS, 25 (78%) had HR APOL1. Compared to children with low risk APOL1 and FSGS (comprising 36 non-AA and 7 AA), children with HR APOL1 developed FSGS at a later age, 12.0 (IQR: 9.5, 12.5) vs. 5.5 (2.5, 11.5) years, p = 0.004, had a higher prevalence of uncontrolled hypertension (52 vs. 33%, p = 0.13), left ventricular hypertrophy (LVH) (53 vs. 12%, p < 0.01), C-reactive protein > 3 mg/l (33 vs. 15%, p = 0.12), and obesity (48 vs. 19%, p = 0.01). There were no differences in glomerular filtration rate, hemoglobin, iPTH, or calcium-phosphate product. AA children with HR APOL1 genotype and FSGS have increase prevalence of obesity and LVH despite a later age of FSGS onset, while adjusting for socioeconomic status. Treatment of obesity may be an important component of chronic kidney disease and LVH management in this population.

Fibroblast Growth Factor 23 and Risk of CKD Progression in Children.

Plasma fibroblast growth factor 23 (FGF23) concentrations increase early in the course of CKD in children. High FGF23 levels associate with progression of CKD in adults. Whether FGF23 predicts CKD progression in children is unknown. We tested the hypothesis that high plasma FGF23 is an independent risk factor for CKD progression in 419 children, aged 1-16 years, enrolled in the Chronic Kidney Disease in Children (CKiD) cohort study. We measured plasma FGF23 concentrations at baseline and determined GFR annually using plasma disappearance of iohexol or the CKiD study estimating equation. We analyzed the association of baseline FGF23 with risk of progression to the composite end point, defined as start of dialysis or kidney transplantation or 50% decline from baseline GFR, adjusted for demographics, baseline GFR, proteinuria, other CKD-specific factors, and other mineral metabolites. At enrollment, median age was 11 years [interquartile range (IQR), 8-15], GFR was 44 ml/min per 1.73 m2 (IQR, 33-57), and FGF23 was 132 RU/ml (IQR, 88-200). During a median follow-up of 5.5 years (IQR, 3.5-6.6), 32.5% of children reached the progression end point. Higher FGF23 concentrations were independently associated with higher risk of the composite outcome (fully adjusted hazard ratio, 2.52 in the highest versus lowest FGF23 tertile; 95% confidence interval, 1.44 to 4.39, P=0.002; fully adjusted hazard ratio, 1.33 per doubling of FGF23; 95% confidence interval, 1.13 to 1.56, P=0.001). The time to progression was 40% shorter for participants in the highest compared with the lowest FGF23 tertile. In contrast, serum phosphorus, vitamin D metabolites, and parathyroid hormone did not consistently associate with progression in adjusted analyses. High plasma FGF23 is an independent risk factor for CKD progression in children.

182 URINARY INCONTINENCE AND QUALITY OF LIFE IN THE CHRONIC KIDNEY DISEASE IN CHILDREN LONGITUDINAL COHORT

You have accessJournal of UrologyPediatrics: Dysfunctional Voiding/Enuresis1 Apr 2013182 URINARY INCONTINENCE AND QUALITY OF LIFE IN THE CHRONIC KIDNEY DISEASE IN CHILDREN LONGITUDINAL COHORT Jennifer Dodson, Matthew Matheson, Christopher Cox, Susan Mendley, Susan Massengill, Bradley Warady, and Susan Furth Jennifer DodsonJennifer Dodson Baltimore, MD More articles by this author , Matthew MathesonMatthew Matheson Baltimore, MD More articles by this author , Christopher CoxChristopher Cox Baltimore, MD More articles by this author , Susan MendleySusan Mendley Baltimore, MD More articles by this author , Susan MassengillSusan Massengill Charlotte, NC More articles by this author , Bradley WaradyBradley Warady Kansas City, MO More articles by this author , and Susan FurthSusan Furth Philadelphia, PA More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2013.02.1562AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Urinary incontinence is common among children with Chronic Kidney Disease, and has been shown to have negative effects on Health Related Quality of Life. We sought to assess the prevalence of daytime and nighttime urinary incontinence in the Chronic Kidney Disease in Children (CKiD) longitudinal cohort study, and to determine the association of urinary incontinence with quality of life in this population. METHODS The CKiD study is a prospective, observational cohort of children recruited from 47 sites in the US and Canada. Eligibility requirements include age 1 to 16 yr and estimated glomerular filtration rate (GFR) via Schwartz formula (kHt(cm)/Scr) 30 to 90 ml/min/1.73 m2. Data was collected at yearly visits after baseline until renal replacement therapy or other endpoint was reached. The analysis was restricted to children 5 years and older. Self-reported day and night wetness were assessed at yearly visits. Multivariate median regressions were used to investigate the effects of wetness status on median PedsQL scores, adjusting for catheterization status, age, sex, race, maternal education, income, underlying etiology of CKD, GFR, hemoglobin, height %ile, proteinuria, and IQ. Bootstrapping was utilized to account for repeated measurements for the computation of standard errors and confidence intervals. RESULTS The median baseline age of the 575 participants was 10.8 years, 61% were male, 23% were African-American and 60% had a urological disorder. The participants contributed a median of 4 years of follow-up. There were a total of 1,953 visits, of which 1,363 had wetness data available. 143 (28%) of participants ever reported having daytime wetness, 218 (43%) ever reported having nighttime wetness, and 116 (23%) ever performed catheterization. Daytime wetness lowered median PedsQL scores by 7.3 points (95% CI: -12.2, -1.0, p=0.019) on the child reported physical domain, while nighttime wetness did not significantly reduce median PedsQL score in fully adjusted models. Similarly, daytime wetness lowered Parent-reported median PedsQL physical domain scores by 6.2 points (95% CI: -11.4, 0.4, p=0.068). CONCLUSIONS Among children in the CKiD cohort, daytime incontinence was associated with worse self-reported HRQOL, specifically within the PedsQL child-reported physical domain. On longitudinal follow-up, these findings show persistent negative effects of daytime incontinence, and suggest that management of urinary incontinence may improve QOL in this population. © 2013 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 189Issue 4SApril 2013Page: e74-e75 Advertisement Copyright & Permissions© 2013 by American Urological Association Education and Research, Inc.MetricsAuthor Information Jennifer Dodson Baltimore, MD More articles by this author Matthew Matheson Baltimore, MD More articles by this author Christopher Cox Baltimore, MD More articles by this author Susan Mendley Baltimore, MD More articles by this author Susan Massengill Charlotte, NC More articles by this author Bradley Warady Kansas City, MO More articles by this author Susan Furth Philadelphia, PA More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Urological Disorders in Chronic Kidney Disease in Children Cohort: Clinical Characteristics and Estimation of Glomerular Filtration Rate

Urological disorders are the most common cause of pediatric chronic kidney disease. We determined the characteristics of children with urological disorders and assessed the agreement between the newly developed bedside glomerular filtration rate estimating formula with measured glomerular filtration rate in 586 patients in the Chronic Kidney Disease in Children study. The Chronic Kidney Disease in Children study is a prospective, observational cohort of children recruited from 48 sites in the United States and Canada. Eligibility requirements include age 1 to 16 years and estimated glomerular filtration rate by original Schwartz formula 30 to 90 ml/min/1.73 m(2). Baseline demographics, clinical variables and glomerular filtration rate were assessed. Bland-Altman analysis was conducted to assess agreement between estimated and measured glomerular filtration rates. Of the 586 participants with at least 1 glomerular filtration rate measurement 348 (59%) had an underlying urological diagnosis (obstructive uropathy in 118, aplastic/hypoplastic/dysplastic kidneys in 104, reflux in 87 and other condition in 39). Among these patients median age was 9 years, duration of chronic kidney disease was 7 years and age at first visit with a urologist was less than 1 year. Of the patients 67% were male, 67% were white and 21% had a low birth weight. Median height was in the 24th percentile. Median glomerular filtration rate as measured by iohexol plasma disappearance was 44.8 ml/min/1.73 m(2). Median glomerular filtration rate as estimated by the Chronic Kidney Disease in Children bedside equation was 44.3 ml/min/1.73 m(2) (bias = -0.5, 95% CI -1.7 to 0.7, p = 0.44). Underlying urological causes of chronic kidney disease were present in 59% of study participants. These children were diagnosed early in life, and many had low birth weight and growth delay. There is good agreement between the newly developed Chronic Kidney Disease in Children estimating equations and measured glomerular filtration rate in this population.

Design and Methods of the Chronic Kidney Disease in Children (CKiD) Prospective Cohort Study

An estimated 650,000 Americans will have ESRD by 2010. Young adults with kidney failure often develop progressive chronic kidney disease (CKD) in childhood and adolescence. The Chronic Kidney Disease in Children (CKiD) prospective cohort study of 540 children aged 1 to 16 yr and have estimated GFR between 30 and 75 ml/min per 1.73 m2 was established to identify novel risk factors for CKD progression; the impact of kidney function decline on growth, cognition, and behavior; and the evolution of cardiovascular disease risk factors. Annually, a physical examination documenting height, weight, Tanner stage, and standardized BP is conducted, and cognitive function, quality of life, nutritional, and behavioral questionnaires are completed by the parent or the child. Samples of serum, plasma, urine, hair, and fingernail clippings are stored in biosamples and genetics repositories. GFR is measured annually for 2 yr, then every other year using iohexol, HPLC creatinine, and cystatin C. Using age, gender, and serial measurements of Tanner stage, height, and creatinine, compared with iohexol GFR, a formula to estimate GFR that will improve on traditional pediatric GFR estimating equations when applied longitudinally is expected to be developed. Every other year, echocardiography and ambulatory BP monitoring will assess risk for cardiovascular disease. The primary outcome is the rate of decline of GFR. The CKiD study will be the largest North American multicenter study of pediatric CKD.