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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: Ambulatory blood pressure monitoring (ABPM) is routinely performed in children with chronic kidney disease to identify masked hypertension, a risk factor for accelerated chronic kidney disease progression. However, ABPM is burdensome, and developing an accurate prediction of masked hypertension may allow using ABPM selectively rather than routinely.Methods: To create a prediction model for masked hypertension using clinic blood pressure (BP) and other clinical characteristics, we analyzed 809 ABPM studies with nonhypertensive clinic BP among the participants of the Chronic Kidney Disease in Children study.Results: Masked hypertension was identified in 170 (21.0%) observations. We created prediction models for masked hypertension via gradient boosting, random forests, and logistic regression using 109 candidate predictors and evaluated its performance using bootstrap validation. The models showed C statistics from 0.660 (95% CI, 0.595-0.707) to 0.732 (95% CI, 0.695-0.786) and Brier scores from 0.148 (95% CI, 0.141-0.154) to 0.167 (95% CI, 0.152-0.183). Using the possible thresholds identified from this model, we stratified the dataset by clinic systolic/diastolic BP percentiles. The prevalence of masked hypertension was the lowest (4.8%) when clinic systolic/diastolic BP were both <20th percentile, and relatively low (9.0%) with clinic systolic BP<20th and diastolic BP<80th percentiles. Above these thresholds, the prevalence was higher with no discernable pattern.Conclusions: ABPM could be used selectively in those with low clinic BP, for example, systolic BP<20th and diastolic BP<80th percentiles, although careful assessment is warranted as masked hypertension was not completely absent even in this subgroup. Above these clinic BP levels, routine ABPM remains recommended. [ABSTRACT FROM AUTHOR]

Over the past 2 decades, cardiovascular (CV) disease has been recognized as one of the most important complications of chronic kidney disease (CKD) and one of the leading causes of death in children with advanced CKD and in young adults who developed CKD during childhood. CV abnormalities develop early and progress during the course of CKD in children. Characterization of the prevalence and evolution of CV disease risk factors in progressive CKD is one of the primary aims of the Chronic Kidney Disease in Children study. In this review, we summarize up-to-date findings from the Chronic Kidney Disease in Children study with a focus on traditional and CKD-related CV risk factors and early subclinical markers of cardiac and vascular structure and function. We also discuss the effect of CV risk factors on progression of CKD. [ABSTRACT FROM AUTHOR]

Objective: To estimate the prevalence of metabolic syndrome (MetS) and examine its association with chronic kidney disease progression in children enrolled in the Chronic Kidney Disease in Children study.Study Design: MetS was defined as being overweight or obese and having ≥2 cardiometabolic risk factors (CMRFs). Incidence and prevalence of MetS were assessed using pairs of visits approximately 2 years apart.Results: A total of 799 pairs of person-visits (contributed by 472 children) were included in the final analysis. Of these, 70% had a normal body mass index (BMI), 14% were overweight, and 16% were obese. At the first visit, the prevalence of MetS in the overweight group was 40% and in the obese group was 60%. In adjusted models, annual percent estimated glomerular filtration rate decline in those who had normal BMI and incident or persistent multiple CMRFs or those with persistent MetS was -6.33%, -6.46%, and -6.08% (respectively) compared with children who never had multiple CMRFs (-3.38%, P = .048, .045, and .036, respectively). Children with normal BMI and incident multiple CMRFs and those with persistent MetS had approximately twice the odds of fast estimated glomerular filtration rate decline (>10% per year) compared with those without multiple CMRFs and normal BMI.Conclusion: Children with chronic kidney disease have a high prevalence of MetS. These children as well as those with normal BMI but multiple CMRFs experience a faster decline in kidney function. [ABSTRACT FROM AUTHOR]

Children with chronic kidney disease have a markedly increased risk of cardiovascular morbidity and children with end stage renal disease have an estimated 30 times greater risk of cardiovascular mortality than the general pediatric population. In adults, the link between hypertension and cardiovascular disease is well-documented but that association has not been so readily apparent in children with chronic kidney disease. This may be in part because the early changes in blood pressure that occur in these patients do not necessarily manifest with changes in casual blood pressure measurements. Ambulatory blood pressure monitoring, with its ability to gather multiple readings both during the normal activities of the day and the night, is felt to be a more veritable measure of blood pressure. Its use in children has been hampered by limited data on normative values and difficulties in blood pressure classification, while its use in adults is ever expanding. However, with an increasing number of studies in children with chronic kidney disease, ambulatory blood pressure has revealed a greater prevalence of abnormal findings in this population and has been shown to better predict cardiovascular risk than current standards. Two large multi-center studies in Europe and North America have revealed even greater utility of ambulatory blood pressure measures in this population. It is hoped that continued use of ambulatory monitoring in children will help overcome some of its perceived limitations while also validating its use in those at high risk of cardiovascular morbidity. [ABSTRACT FROM AUTHOR]

Cardiovascular disease is a leading cause of morbidity and mortality in patients with chronic kidney disease (CKD), accounting for 50% of deaths of patients on dialysis, even young adults. The etiology of accelerated cardiovascular disease in these patients is likely multifactorial. Although patients with CKD demonstrate a high prevalence of traditional risk factors for cardiovascular disease, these risk factors alone cannot explain the high burden of cardiovascular disease in this patient population. One of several uremia-related risk factors thought to contribute to disease progression is low-grade systemic inflammation. This review summarizes the current literature on the role of inflammation in promoting cardiovascular disease in this patient population as well as potential therapies to address this non-traditional risk factor. [ABSTRACT FROM AUTHOR]

Dyslipidemia, a known risk factor for atherosclerosis, is frequent among both adults and children with chronic kidney disease. Here, we describe the prevalence and pattern of dyslipidemia from a cross-sectional analysis of 391 children aged 1-16 years, enrolled in the multicenter Chronic Kidney Disease in Children (CKiD) study, with a median glomerular filtration rate (GFR), measured by the plasma disappearance of iohexol, of 43 ml/min per 1.73 m2. Multivariate analysis was applied to adjust for age, gender, body mass index (BMI), GFR, and the urinary protein/creatinine ratio. Proteinuria was in the nephrotic range in 44 and the BMI exceeded the 95th percentile in 57 patients of this cohort. Baseline lipid analysis found a high prevalence of hypertriglyceridemia in 126, increased non-HDL-C in 62, and reduced HDL-C in 83. Overall, 177 children had dyslipidemia, of whom 79 had combined dyslipidemia. Lower GFR was associated with higher triglycerides, lower HDL-C, and higher non-HDL-C. Nephrotic-range proteinuria was significantly associated with dyslipidemia and combined dyslipidemia. Compared with children with a GFR >50, children with a GFR <30 had significantly increased odds ratios for any dyslipidemia or for combined dyslipidemia. Hence, among children with moderate chronic kidney disease, dyslipidemia is common and is associated with lower GFR, nephrotic proteinuria, and non-renal factors including age and obesity. [ABSTRACT FROM AUTHOR]