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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).

Hypertension is frequent in children with chronic kidney disease (CKD). Its prevalence varies according to CKD stage and cause. It is relatively uncommon in children with congenital kidney disease, while acquired kidney disease is associated with a higher prevalence of hypertension. Studies in children with CKD utilizing ambulatory blood pressure monitoring also showed a high prevalence of masked hypertension. Uncontrolled and longstanding hypertension in children is associated with progression of CKD. Aggressive treatment of high blood pressure should be an essential part of care to delay CKD progression in children., Author(s): Mark M. Mitsnefes [sup.1] , Elke Wühl [sup.2] Author Affiliations: (1) https://ror.org/01hcyya48, grid.239573.9, 0000 0000 9025 8099, Division of Nephrology and Hypertension, Cincinnati Children's Hospital Medical Center, , 3333 [...]

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 m.sup.2 [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. Graphical abstract A higher resolution version of the Graphical abstract is available as Supplementary information, Author(s): Amy J. Kogon [sup.1] , Jennifer Roem [sup.2] , Michael F. Schneider [sup.2] , Mark M. Mitsnefes [sup.3] , Babette S. Zemel [sup.4] , Bradley A. Warady [sup.5] , [...]

Background Chronic kidney disease (CKD) is associated with many comorbidities requiring complex management. We described treatment patterns for common modifiable CKD complications (high blood pressure, anemia, hyperphosphatemia, and acidosis) according to severity of CKD and examined factors associated with the absence of drug therapy, among participants with a persistent comorbidity, for 1 year in children enrolled in the CKiD study. Methods A total of 703 CKiD participants contributed 2849 person-visits over a median 3.5 years of follow-up. Using pairs of annual visits, we examined whether participants with abnormal biomarker levels at the first (index) visit persisted in the abnormal levels 1 year later according to CKD risk stage. Multivariate analyses identified demographic and clinical factors associated with the absence of drug therapy among those with persistent comorbid conditions for 1 year. Results The overall proportions of person-visits prescribing therapy at 1-year follow-up for treating anemia, acidosis, hyperphosphatemia, and high blood pressure were 54%, 45%, 29%, and 81%, respectively. The frequency of therapy increased with advanced CKD risk stage for all comorbidities; however, 19-23% of participants with acidosis, 24-27% with anemia, and 30-39% with hyperphosphatemia at high-risk stages (E and F) were not prescribed appropriate therapy despite the persistence of abnormal levels of these biomarkers for at least 1 year. The resolution of comorbidities at advanced CKD stages without treatment was unlikely. Conclusions Many children with CKD in the CKiD cohort did not receive pharmacological treatment for common and persistent modifiable comorbidities, even in severe CKD risk stages. Graphical abstract, Author(s): Yunwen Xu [sup.1] , Derek K Ng [sup.1] , Susan L Furth [sup.2] , Bradley A Warady [sup.3] , Mark M Mitsnefes [sup.4] Author Affiliations: (1) grid.21107.35, 0000 0001 [...]

Background Few studies have examined how changes in BMI [body mass index] over time associate with risk of adverse outcomes in children receiving renal replacement therapy [RRT]. The objective of this study was to examine the association between annualized changes in BMI and the risk of death in children treated with RRT. Methods We performed a retrospective cohort study of 1182 pediatric dialysis and transplant patients in the Pediatric Growth and Development Special Study of the United States Renal Data System. Quintiles of annualized change in BMI z-score (with cutoffs of - 0.50, - 0.13, 0.09, 0.57) were used as the primary predictor, with the middle quintile (- 0.13 to 0.09) serving as the reference category. Cox models were used to examine the association between exposure and death, with time of analysis starting from the second BMI measurement. Results Median follow-up time to death or censoring was 6 years. Median age was 14.6 years, and 61% of children had a functional graft at cohort entry. There was a U-shaped association between BMI change and mortality risk: a large decline in annualized BMI z-score change (> - 0.50) was associated with an increased risk of death (adjusted hazard ratio [aHR] 1.54 (95% CI 1.17-2.03), p = 0.002). A large increase in annualized BMI z-score change (> 0.57) was also associated with an increased risk of death (aHR 1.44 (95% CI 1.07-1.92), p = 0.02). No interaction was noted between annualized BMI change and initial treatment modality (dialysis or transplant, p = 0.15). Conclusions Maintenance of a stable BMI in pediatric patients receiving RRT may be associated with improved survival., Author(s): Matthew J. Roberts [sup.1] , Mark M. Mitsnefes [sup.2] , Charles E. McCulloch [sup.3] , Larry A. Greenbaum [sup.4] , Barbara A. Grimes [sup.3] , Elaine Ku [sup.5] [sup.6] [...]

Background The 2011 annual report of the North American Pediatric Renal Transplant Cooperative Study (NAPRTCS) registry comprises data on 6482 dialysis patients over the past 20 years of the registry. Methods The study compared clinical parameters and patient survival in the first 10 years of the registry (1992-2001) with the last decade of the registry (2002-2011). Results There was a significant increase in hemodialysis as the initiating dialysis modality in the most recent cohort (42% vs. 36%, p < 0.001). Patients in the later cohort were less likely to have a hemoglobin Conclusions The survival of pediatric patients on chronic dialysis has improved over two decades of dialysis registry data, specifically for children, Author(s): Donald J. Jr Weaver [sup.1] , Michael J. G. Somers [sup.2] [sup.3] , Karen Martz [sup.4] , Mark M. Mitsnefes [sup.5] Author Affiliations: (1) Division of Nephrology and Hypertension, [...]

Background Left ventricular (LV) systolic dysfunction is a relatively uncommon but serious complication of pediatric chronic kidney disease, and may be related to uremia and uncontrolled hypertension. There is limited information on the strategy for managing these children. In some cases, combined heart-kidney transplant may be considered or kidney transplant delayed until cardiac function improves. It is unknown whether these patients are at increased risk for poor outcomes after kidney transplantation. Methods We conducted a retrospective, multicenter study on the outcomes of children with severe and symptomatic cardiomyopathy who underwent kidney transplantation. Results Eleven patients receiving maintenance dialysis with systolic dysfunction underwent kidney transplantation without simultaneous heart transplant. Nine patients had congestive heart failure in the pre-transplant period. There were no identified complications post-transplant related to the underlying cardiac dysfunction. LV systolic function normalized in all patients and the mean shortening fraction increased from 19.0 ± 4.6 % to 32.0 ± 4.4 % (p < 0.0001). Conclusions Kidney transplantation should be considered for children receiving maintenance dialysis with severe LV dysfunction., Author(s): Sandeep K. Riar[sup.1] , Mark M. Mitsnefes[sup.2] , Edward J. Nehus[sup.2] , Hiren P. Patel[sup.3] , Julia M. Steinke[sup.4] , Teri Crumb[sup.4] , Elizabeth C. Abraham[sup.5] , Margret W. [...]