Investigation of a targeted panel of gut microbiome-derived toxins in children with chronic kidney disease.

Background: The gut-kidney axis is implicated in chronic kidney disease (CKD) morbidity. We describe how a panel of gut microbiome-derived toxins relates to kidney function and neurocognitive outcomes in children with CKD, consisting of indoleacetate, 3-indoxylsulfate, p-cresol glucuronide, p-cresol sulfate, and phenylacetylglutamine.

Methods: The Chronic Kidney Disease in Children (CKiD) cohort is a North American multicenter prospective cohort that enrolled children aged 6 months to 16 years with estimated glomerular filtration rate (eGFR) 30-89 ml/min/1.

Biomarker Panels for Discriminating Risk of CKD Progression in Children.

Background: We have previously studied biomarkers of tubular health (EGF), injury (KIM-1), dysfunction (alpha-1 microglobulin), and inflammation (TNFR-1, TNFR-2, MCP-1, YKL-40, suPAR), and demonstrated that plasma KIM-1, TNFR-1, TNFR-2 and urine KIM-1, EGF, MCP-1, urine alpha-1 microglobulin are each independently associated with CKD progression in children. In this study, we used bootstrapped survival trees to identify a combination of biomarkers to predict CKD progression in children.

Methods: The CKiD Cohort Study prospectively enrolled children 6 months to 16 years old with an eGFR of 30-90 ml/min/1.

Comparison of three different cystatin C measurement procedures in a pediatric chronic kidney disease cohort: Calibration for longitudinal measurements and implications for clinical estimation of GFR.

Introduction: Serum cystatin C (CysC) is used to estimate glomerular filtration rate (eGFR), including in the Chronic Kidney Disease in Children (CKiD) Under 25 years (U25eGFR) equations. Several CysC measurement procedures available from diagnostic vendors include reference material for calibration, but the extent of heterogeneity across manufacturers is unclear. Since heterogeneity may have clinical and research implications for eGFR, we evaluated three CysC procedures in samples from the CKiD study representing a wide spectrum of kidney function.

Culturally Tailored Messages and Trial Registry Enrollment: A Randomized Clinical Trial.

Importance: Marginalized populations have lower levels of clinical trial representation than other populations. Tailoring recruitment materials and providing incentives may improve representation.

Objective: To determine whether culturally tailored video improves parents' decision to enroll (DTE) Black children in a research registry.

Use of 3M-052-AF with Alum adjuvant in HIV trimer vaccine induces human autologous neutralizing antibodies.

Stabilized trimers preserving the native-like HIV envelope structure may be key components of a preventive HIV vaccine regimen to induce broadly neutralizing antibodies (bnAbs). We evaluated trimeric BG505 SOSIP.664 gp140 formulated with a novel TLR7/8 signaling adjuvant, 3M-052-AF/Alum, for safety, adjuvant dose-finding, and immunogenicity in a first-in-healthy adult (n = 17), randomized, and placebo-controlled trial (HVTN 137A).

Hypertension and Left Ventricular Strain in Pediatric Chronic Kidney Disease.

Background: Left ventricular global longitudinal strain (LV GLS) on echocardiography is a sensitive yet clinically significant marker of myocardial dysfunction. Reduced LV GLS is prevalent in adults with chronic kidney disease and hypertension and is associated with adverse cardiovascular outcomes. It may be a biomarker of chronic kidney disease-associated myocardial dysfunction in children, but data are limited.

Patient, Parental, and Health Professional Perspectives on Growth in Children With CKD.

Rationale & Objective: Growth failure is a common problem among children with chronic kidney disease (CKD). Reduced height is associated with psychosocial burden, social stigma, and impaired quality of life. This study describes the aspects of growth impairment that are most impactful from the perspectives of children with CKD, their parents, and health professionals.

Clinical characteristics and favorable treatment responses of recurrent focal segmental glomerulosclerosis or steroid-resistant nephrotic syndrome in children after kidney transplantation.

Background: Recurrence of focal segmental glomerulosclerosis (FSGS) or steroid-resistant nephrotic syndrome (SRNS) after kidney transplant leads to significant morbidity and potentially earlier allograft loss. To date however, reported rates, risk factors and treatment outcomes have varied widely.

Methods: We applied computational phenotypes to a multicenter aggregation of electronic health records data from 7 large pediatric health systems in the USA, to identify recurrence rates, risk factors, and treatment outcomes.

Vitamin D and its associations with blood pressure in the Chronic Kidney Disease in Children (CKiD) cohort.

Background: Vitamin D (25OHD) can modulate pathways and mechanisms that regulate blood pressure (BP). Observational studies in children and adults have shown an inverse association between 25OHD and BP. Studies evaluating associations between 25OHD and BP in pediatric chronic kidney disease are limited.

Consistency of metabolite associations with measured glomerular filtration rate in children and adults.

Background: There is interest in identifying novel filtration markers that lead to more accurate GFR estimates than current markers (creatinine and cystatin C) and are more consistent across demographic groups. We hypothesize that large-scale metabolomics can identify serum metabolites that are strongly influenced by glomerular filtration rate (GFR) and are more consistent across demographic variables than creatinine, which would be promising filtration markers for future investigation.

Methods: We evaluated the consistency of associations between measured GFR (mGFR) and 887 common, known metabolites quantified by an untargeted chromatography- and spectroscopy-based metabolomics platform (Metabolon) performed on frozen blood samples from 580 participants in Chronic Kidney Disease in Children (CKiD), 674 participants in Modification of Diet in Renal Disease (MDRD) Study and 962 participants in African American Study of Kidney Disease and Hypertension (AASK).

HIV BG505 SOSIP.664 trimer with 3M-052-AF/alum induces human autologous tier-2 neutralizing antibodies.

Unlabelled: Stabilized trimers preserving the native-like HIV envelope structure may be key components of a preventive HIV vaccine regimen to induce broadly neutralizing antibodies (bnAbs). We evaluated trimeric BG505 SOSIP.664 gp140, formulated with a novel TLR7/8 signaling adjuvant, 3M-052-AF/Alum, for safety, adjuvant dose-finding and immunogenicity in a first-in-healthy adult (n=17), randomized, placebo-controlled trial (HVTN 137A).

Psychotropic Medication Usage in Pediatric CKD: Reporting from the CKD in Children Cohort.

Key Points: Psychotropic medication use is prevalent in the pediatric CKD population. Central nervous system stimulant usage was more common in male patients, and antidepressant usage was more frequently reported at follow-up visits during teenage years.

Background: Mental health disorders within the pediatric CKD population are prevalent.

Longitudinal Plasma Metabolome Patterns and Relation to Kidney Function and Proteinuria in Pediatric CKD.

Key Points: Longitudinal untargeted metabolomics. Children with CKD have a circulating metabolome that changes over time.

Background: Understanding plasma metabolome patterns in relation to changing kidney function in pediatric CKD is important for continued research for identifying novel biomarkers, characterizing biochemical pathophysiology, and developing targeted interventions.

Trials and Tribulations - The Challenges of Clinical Trials in Children.

In this issue of 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. In June 2023, following another pivotal trial, the U.

Adenotonsillectomy for Snoring and Mild Sleep Apnea in Children: A Randomized Clinical Trial.

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.

Evaluation of novel candidate filtration markers from a global metabolomic discovery for glomerular filtration rate estimation.

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.

Pubertal luteinizing hormone levels in children with chronic kidney disease and association with change in glomerular filtration rate.

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.

Plasma Metabolomics of Dietary Intake of Protein-Rich Foods and Kidney Disease Progression in Children.

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.

Associations between anemia and FGF23 in the CKiD study.

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.

Association Between Dialysis Facility Ownership and Mortality Risk in Children With Kidney Failure.

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.