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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).

Background Recombinant growth hormone (rGH) is an efficacious therapy for growth failure in children with chronic kidney disease (CKD). We described rGH use and estimated its relationship with growth and kidney function in the Chronic Kidney Disease in Children (CKiD) cohort. Methods Participants included those with growth failure, prevalent rGH users, and rGH initiators who did not meet growth failure criteria. Among those with growth failure, height z scores and GFR were compared between rGH initiators and non-initiators across 42 months. Inverse probability weights accounted for differences in baseline variables in weighted linear regressions. Results Among 148 children with growth failure and no previous rGH therapy, 42 (28%) initiated rGH therapy. Of the initiators, average age was 8.9 years, height z score was 2.50 standard deviations (SDs) (0.6.sup.th percentile), and GFR was 44 ml/min/1.73m.sup.2. They were compared to 106 children with growth failure who never initiated therapy (8.8 years, -2.33 SDs, and 51 ml/min/1.73m.sup.2). At 30 and 42 months after rGH, height increased +0.26 (95%CI: -0.11, +0.62) and +0.35 (95%CI: -0.17, +0.87) SDs, respectively, relative to those who did not initiate rGH. rGH was not associated with GFR. Conclusions Participants with growth failure receiving rGH experienced significant growth, although this was attenuated relative to RCTs, and were more likely to have higher household income and lower GFR. A substantial number of participants, predominantly boys, without diagnosed growth failure received rGH and had the highest achieved height relative to mid-parental height. Since rGH was not associated with accelerated GFR decline, increasing rGH use in this population is warranted., Author(s): Derek K. Ng [sup.1] , Megan K. Carroll [sup.1] , Frederick J. Kaskel [sup.2] , Susan L. Furth [sup.3] [sup.4] , Bradley A. Warady [sup.5] , Larry A. Greenbaum [...]

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 [greater than or equal to] 85th to 95th percentile) and 115 obese (BMI [greater than or equal to] 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., Author(s): Nancy M. Rodig [sup.1] , Jennifer Roem [sup.2] , Michael F. Schneider [sup.2] , Patricia W. Seo-Mayer [sup.3] , Kimberly J. Reidy [sup.4] , Frederick J. Kaskel [sup.4] , [...]

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., Author(s): Julien Hogan [sup.1] [sup.2] , Michael F. Schneider [sup.3] , Rima Pai [sup.1] , Michelle R. Denburg [sup.4] , Amy Kogon [sup.4] , Ellen R. Brooks [sup.5] , Frederick [...]

Author(s): Abby Basalely [sup.1] , Diane Liu [sup.1] , Frederick J. Kaskel [sup.1] Author Affiliations: (1) grid.414114.5, 0000 0004 0566 7955, Department of Pediatrics, Division of Pediatric Nephrology, The Children's [...]

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

The formation of steroid resistance in children with nephrotic syndrome (NS) who were initially steroid responsive was described decades ago but has not been studied in suificient depth. Except for the International Study of Kidney Disease in Children, conducted more than three decades ago, when only cyclophosphamide was available as a second-line agent in steroid-resistant NS, only a handful of small studies have addressed the problem of late steroid resistance (LSR) over the past 40 years. Epidemiology and risk factors for the formation of LSR and differences in outcomes when compared with initial steroid resistance still remain unknown. While multiple second-line treatment choices (calcineurin inhibitors, mycophenolate mofetil, rituximab) exist today, therapeutic approaches to the patients with LSR remain empirical, as no evidence-based data have become available. In the current issue of Pediatric Nephrology, Straatmann et al. report retrospective data on the treatment outcomes for 29 pediatric NS patients with LSR from eight participating centers of the Midwest Pediatric Research Consortium. The authors describe a current pattern of second-line agents used in their cohort and show that the majority of patients (66 %) achieved complete or partial remission after a period of observation for 85[+ or -]47 months. The authors also describe the data on renal histology. While these data represent an important step forward in our understanding of LSR, further work is needed before firm clinical recommendations can be made. Large-scale prospective studies are required to answer important questions about the epidemiology, genetics and outcomes in late steroid-resistant NS, explore the role of medication adherence and develop evidence-based practice guidelines. Keywords Nephrotic syndrome * Late steroid resistance * Immunosuppressant therapy * Focal segmental glomerulosclerosis * Outcome of nephrotic syndrome, Classification of childhood nephrotic syndrome (NS) based on initial steroid responsiveness is not absolute as some initially steroid-sensitive patients may later develop steroid resistance--a phenomenon that was recognized decades ago. [...]

Abstract Mice lacking CD2-associated protein (CD2AP-/-) develop glomerular lesions resembling human focal segmental glomerulosclerosis (FSGS) between 3-4 weeks of age and die approximately 2 weeks later from massive proteinuria and [...]