Susan Furth

UNLABELLED: Alport syndrome is a hereditary chronic kidney disease, attributed to rare pathogenic variants in either of three collagen genes ( COL4A3/4/5 ) with most localized in COL4A5 . Trimeric type IV Collagen α3α4α5 is essential for the glomerular basement membrane that forms the kidney filtration barrier. A means to functionally assess the many candidate variants and determine pathogenicity is urgently needed. We used Drosophila , an established model for kidney disease, and identify Col4a1 as the functional homolog of human COL4A5 in the fly nephrocyte (equivalent of human podocyte)...

In this issue of NEJM Evidence, we see the results of a randomized clinical trial of dapagliflozin or saxagliptin in pediatric type 2 diabetes (T2D). In children and adolescents with T2D, dapagliflozin achieved significant improvements in glycemia in the trial.1 In June 2023, following another pivotal trial, the U.S. Food and Drug Administration (FDA) approved empagliflozin and the combination of empagliflozin and metformin as additions to diet and exercise to improve blood sugar control in children 10 years and older with T2D...

IMPORTANCE: The utility of adenotonsillectomy in children who have habitual snoring without frequent obstructive breathing events (mild sleep-disordered breathing [SDB]) is unknown. OBJECTIVES: To evaluate early adenotonsillectomy compared with watchful waiting and supportive care (watchful waiting) on neurodevelopmental, behavioral, health, and polysomnographic outcomes in children with mild SDB. DESIGN, SETTING, AND PARTICIPANTS: Randomized clinical trial enrolling 459 children aged 3 to 12...

Creatinine and cystatin-C are recommended for estimating glomerular filtration rate (eGFR) but accuracy is suboptimal. Here, using untargeted metabolomics data, we sought to identify candidate filtration markers for a new targeted assay using a novel approach based on their maximal joint association with measured GFR (mGFR) and with flexibility to consider their biological properties. We analyzed metabolites measured in seven diverse studies encompasing 2,851 participants on the Metabolon H4 platform that had Pearson correlations with log mGFR and used a stepwise approach to develop models to < -0...

BACKGROUND: Children with chronic kidney disease (CKD) are at risk for abnormalities in pubertal development. We aimed to describe the timing of pubertal onset by luteinizing hormone (LH) levels and the association between hormonal onset of puberty with changes in GFR. METHODS: Data from the Chronic Kidney Disease in Children (CKiD) study were collected prospectively. GFR was estimated at annual visits and measured by iohexol clearance every other year. LH was measured from stored repository serum samples in a nested sample of 124 participants...

OBJECTIVE: Evidence regarding the efficacy of a low-protein diet for patients with CKD is inconsistent and recommending a low-protein diet for pediatric patients is controversial. There is also a lack of objective biomarkers of dietary intake. The purpose of this study was to identify plasma metabolites associated with dietary intake of protein and to assess whether protein-related metabolites are associated with CKD progression. METHODS: Nontargeted metabolomics was conducted in plasma samples from 484 Chronic Kidney Disease in Children (CKiD) participants...

BACKGROUND: Children with CKD are at risk for impaired neurocognitive functioning. We investigated metabolomic associations with neurocognition in children with CKD. METHODS: We leveraged data from the Chronic Kidney Disease in Children (CKiD) study and the Neurocognitive Assessment and Magnetic Resonance Imaging Analysis of Children and Young Adults with Chronic Kidney Disease (NiCK) study. CKiD is a multi-institutional cohort that enrolled children aged 6 months to 16 years with eGFR 30-90 ml/min per 1...

INTRODUCTION: Despite recognized geographic and sex-based differences in hemoglobin in the general population, these factors are typically ignored in patients with chronic kidney disease (CKD) in whom a single therapeutic range for hemoglobin is recommended. We sought to compare the distribution of hemoglobin across international nondialysis CKD populations and evaluate predictors of hemoglobin. METHODS: In this cross-sectional study, hemoglobin distribution was evaluated in each cohort overall and stratified by sex and estimated glomerular filtration rate (eGFR)...

BACKGROUND: Fibroblast 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...

IMPORTANCE: In adults, treatment at profit dialysis facilities has been associated with a higher risk of death. OBJECTIVE: To determine whether profit status of dialysis facilities is associated with the risk of death in children with kidney failure treated with dialysis and whether any such association is mediated by differences in access to transplant. DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study reviewed US Renal Data System records of 15 359 children who began receiving dialysis for kidney failure between January 1, 2000, and December 31, 2019, in US dialysis facilities...

BACKGROUND: Collagen X biomarker (CXM) is a novel biomarker of linear growth velocity. We investigated whether CXM correlated with measured growth velocity in children with impaired kidney function. METHODS: We used data from children aged 2 through 16 years old enrolled in the Chronic Kidney Disease in Children (CKiD) study. We assessed the association between CXM level and growth velocity based on height measurements obtained at study visits using linear regression models constructed separately by sex, with and without adjustment for CKD covariates...

BACKGROUND: Nonadherence is common in children with chronic kidney disease (CKD). This may contribute to inadequate blood pressure control and adverse outcomes. This study examined associations between antihypertensive medication nonadherence, ambulatory blood pressure monitoring (ABPM) parameters, kidney function, and cardiac structure among children with CKD. METHODS: We performed secondary analyses of data from the CKD in Children (CKiD) study, including participants with treated hypertension who underwent ABPM, laboratory testing, and echocardiography biannually...

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...

BACKGROUND: Cardiovascular disease (CVD) is the most common cause of mortality in chronic kidney disease (CKD). Children with early-onset CKD arguably experience the greatest lifetime CVD burden. We utilized data from the Chronic Kidney Disease in Children Cohort Study (CKiD) to evaluate two pediatric CKD cohorts: congenital anomalies of the kidney and urinary tract (CAKUT) and cystic kidney disease for CVD risks and outcomes. METHODS: CVD risk factors and outcomes including blood pressures, left ventricular hypertrophy (LVH), left ventricular mass index (LVMI), and ambulatory arterial stiffness index (AASI) scores were evaluated...

BACKGROUND: 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. METHODS: 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...

BACKGROUND: The objective was to determine the extent that eGFR formulas correspond to measured plasma iohexol clearance (iGFR) in children with normal or near normal kidney function, particularly how different eGFR formulas yield discordant results. METHODS: iGFR from 2 (iGFR-2pt) and 4 (iGFR-4pt) time points along with creatinine and/or cystatin C-based eGFR were measured in children with mild CKD, stages 1-2. eGFR was calculated using 6 equations: 3 under 25 (U25) formulas from the Chronic Kidney Disease in Children (CKiD) study, the full age-combined cystatin C (cysC) and creatinine spectrum (FAS-combined), the European Kidney Function Consortium (EKFC-creatinine) equation, and the Chronic Kidney Disease Epidemiology Collaboration (CKD-epi) cysC-based equation...

Clinicians need improved prediction models to estimate time to kidney replacement therapy (KRT) for children with chronic kidney disease (CKD). Here, we aimed to develop and validate a prediction tool based on common clinical variables for time to KRT in children using statistical learning methods and design a corresponding online calculator for clinical use. Among 890 children with CKD in the Chronic Kidney Disease in Children (CKiD) study, 172 variables related to sociodemographics, kidney/cardiovascular health, and therapy use, including longitudinal changes over one year were evaluated as candidate predictors in a random survival forest for time to KRT...

The goal of this study was to define the glioma-associated microglia/macrophage (GAM) response and associated molecular landscape in canine oligodendrogliomas. Here, we quantified the intratumoral GAM density of low- and high-grade oligodendrogliomas compared to that of a normal brain, as well as the intratumoral concentration of several known GAM-derived pro-tumorigenic molecules in high-grade oligodendrogliomas compared to that in a normal brain. Our analysis demonstrated marked intra- and intertumoral heterogeneity of GAM infiltration...

BACKGROUND: In children with chronic kidney disease (CKD), certain risk factors are associated with faster eGFR decline and earlier kidney failure. Whether these factors have lingering effects on post-transplant eGFR trajectory remains unclear. We characterized pre- and post-transplant eGFR trajectories in pediatric kidney transplant recipients by their pre-kidney replacement therapy (KRT) risk factors. METHODS: We studied eGFR trajectories before KRT initiation and after transplantation among Chronic Kidney Disease in Children (CKiD) Study participants...

BACKGROUND: IgA vasculitis is the most common vasculitis in children and is often complicated by acute nephritis (IgAVN). Risk of chronic kidney disease (CKD) among children with IgAVN remains unknown. This study aimed to describe the clinical management and kidney outcomes in a large cohort of children with IgAVN. METHODS: This observational cohort study used the PEDSnet database to identify children diagnosed with IgAV between January 1, 2009, and February 29, 2020...