Hyperkalemia in pediatric chronic kidney disease.

BACKGROUND: While hyperkalemia is well described in adult chronic kidney disease (CKD), large studies evaluating potassium trends and risk factors for hyperkalemia in pediatric CKD are lacking. This study aimed to characterize hyperkalemia prevalence and risk factors in pediatric CKD. METHODS: Cross-sectional analysis of Chronic Kidney Disease in Children (CKiD) study data evaluated median potassium levels and percentage of visits with hyperkalemia (K ≥5.5 mmoL/L) in relation to demographics, CKD stage, etiology, proteinuria, and acid-base status. Multiple logistic regression was used to identify risk factors for hyperkalemia. RESULTS: One thousand and fifty CKiD participants with 5183 visits were included (mean age 13.1 years, 62.7% male, 32.9% self-identifying as African American or Hispanic). A percentage of 76.6% had non-glomerular disease, 18.7% had CKD stage 4/5, 25.8% had low CO2, and 54.2% were receiving ACEi/ARB therapy. Unadjusted analysis identified a median serum potassium level of 4.5 mmol/L (IQR 4.1-5.0, p <0.001) and hyperkalemia in 6.6% of participants with CKD stage 4/5. Hyperkalemia was present in 14.3% of visits with CKD stage 4/5 and glomerular disease. Hyperkalemia was associated with low CO2 (OR 7.72, 95%CI 3.05-19.54), CKD stage 4/5 (OR 9.17, 95%CI 4.02-20.89), and use of ACEi/ARB therapy (OR 2.14, 95%CI 1.36-3.37). Those with non-glomerular disease were less frequently hyperkalemic (OR 0.52, 95%CI 0.34-0.80). Age, sex, and race/ethnicity were not associated with hyperkalemia. CONCLUSIONS: Hyperkalemia was observed more frequently in children with advanced stage CKD, glomerular disease, low CO2, and ACEi/ARB use. These data can help clinicians identify high-risk patients who may benefit from earlier initiation of potassium-lowering therapies. A higher resolution version of the Graphical abstract is available as Supplementary information.

Longitudinal changes in uric acid concentration and their relationship with chronic kidney disease progression in children and adolescents.

BACKGROUND: Elevated serum uric acid concentration is a risk factor for CKD progression. Its change over time and association with CKD etiology and concomitant changes in estimated glomerular filtration rate (eGFR) in children and adolescents are unknown. METHODS: Longitudinal study of 153 children/adolescents with glomerular (G) and 540 with non-glomerular (NG) etiology from the CKD in Children (CKiD) study. Baseline serum uric acid, change in uric acid and eGFR over time, CKD etiology, and comorbidities were monitored. Adjusted linear mixed-effects regression models quantified the relationship between within-person changes in uric acid and concurrent within-person changes in eGFR. RESULTS: Participants with stable uric acid over follow-up had CKD progression which became worse for increased baseline uric acid (average annual percentage changes in eGFR were - 1.4%, - 7.7%, and - 14.7% in those with G CKD with baseline uric acid < 5.5 mg/dL, 5.5 - 7.5 mg/dL, and > 7.5 mg/dL, respectively; these changes were - 1.4%, - 4.1%, and - 8.6% in NG CKD). Each 1 mg/dL increase in uric acid over follow-up was independently associated with significant concomitant eGFR decreases of - 5.7% (95%CI - 8.4 to - 3.0%) (G) and - 5.1% (95%CI - 6.3 to - 4.0%) (NG) for those with baseline uric acid < 5.5 mg/dL and - 4.3% (95%CI - 6.8 to - 1.6%) (G) and - 3.3% (95%CI - 4.1 to - 2.6%) (NG) with baseline uric acid between 5.5 and 7.5 mg/dL. CONCLUSIONS: Higher uric acid levels and increases in uric acid over time are risk factors for more severe progression of CKD in children and adolescents. A higher resolution version of the Graphical abstract is available as Supplementary information.

Low variability of plant protein intake in the CKiD cohort does not demonstrate changes in estimated GFR nor electrolyte balance.

BACKGROUND: Vegetable or plant-based sources of protein may confer health benefits in children with progressive kidney disease. Our aims were to understand the effect of the proportion of vegetable protein intake on changes in estimated GFR and to understand the effect of the proportion of vegetable protein intake on serum levels of bicarbonate, phosphorus, and potassium. METHODS: Children with baseline eGFR between 30 and 90 mL/min/1.73 m2 were recruited from 59 centers across North America as part of the chronic kidney disease in children (CKiD) study. The percentage of dietary vegetable protein (VP%) was gathered from annual Food Frequency Questionnaires. We performed longitudinal linear mixed models to determine the effect of VP% on eGFR and longitudinal logistic mixed models to determine the effect of VP% on electrolyte balance (potassium, phosphorus, bicarbonate). RESULTS: Two thousand visits from 631 subjects. Across all dichotomized groups of children (sex, African American race, Hispanic ethnicity, glomerular etiology of CKD, hypertension, anemia, hyperkalemia, hyperphosphatemia, acidosis, BMI < 95th percentile), the median VP% was 32-35%. The longitudinal mixed model analysis did not show any effect of VP% on eGFR electrolyte (bicarbonate, phosphorus, and potassium) abnormalities (p > 0.1). CONCLUSIONS: A diverse cohort of children with CKD has a narrow and homogeneous intake of vegetable protein. Due to the low variability of plant-based protein in the cohort, there were no associations between the percentage of plant protein intake and changes in eGFR nor electrolyte balance. A higher resolution version of the Graphical abstract is available as Supplementary information.

Systematic review: associations of calcium intake, vitamin D intake, and physical activity with skeletal outcomes in people with Type 1 diabetes mellitus.

AIMS: The skeletal complications of type 1 diabetes (T1D) include low bone density, poor bone quality and fractures. Greater calcium intake, vitamin D intake, and physical activity are commonly recommended to improve bone health in patients with T1D. However, it is not clear whether these factors are affected by T1D or improve clinical outcomes. METHODS: The objective of this study was to systematically review the literature for evidence of associations between calcium intake, vitamin D intake, and physical activity and skeletal outcomes in T1D. In accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, twenty-two studies were included in this review. RESULTS: The prevalence of calcium deficiency was high and encompassed greater than 50% of participants in the majority of studies. Despite this finding, there was no clear association between calcium intake and bone density in any study. Calcitriol use was associated with gains in bone density in one study but was not associated with changes in bone turnover markers in a second report. No studies specifically investigated the impact of vitamin D2 or D3 supplementation on bone health. Two studies reported a beneficial effect of physical activity interventions on bone accrual in children. The findings from observational studies of physical activity were mixed. CONCLUSION: There are insufficient data to determine if deficient calcium intake, vitamin D intake, or physical activity contributes to the skeletal complications of T1D. Future studies specifically designed to assess the impact of these interventions on the skeleton in T1D participants are needed.

Disordered FGF23 and mineral metabolism in children with CKD.

BACKGROUND AND OBJECTIVES: In children with CKD, information is limited regarding the prevalence and determinants of fibroblast growth factor 23 excess and 1,25-dihyroxyvitamin D deficiency across the spectrum of predialysis CKD. This study characterized circulating concentrations of fibroblast growth factor 23 and 1,25-dihyroxyvitamin D, and investigated their interrelationships and associations with GFR and secondary hyperparathyroidism in children with CKD who were enrolled in the Chronic Kidney Disease in Children observational cohort study. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Plasma fibroblast growth factor 23 concentrations and determinants of mineral metabolism were measured in 464 children ages 1-16 years with predialysis CKD. GFR was measured by plasma disappearance of iohexol in 70% of participants and estimated by the Chronic Kidney Disease in Children estimating equation using serum creatinine and cystatin C concentrations in the remainder of the participants. Participants were grouped according to CKD stage and by 10-ml/min categories of GFR. RESULTS: Median GFR for the cohort was 45 ml/min per 1.73 m(2) (interquartile range=33-57; range=15-109). Plasma fibroblast growth factor 23 concentration was above the normal range in 67% of participants (with higher levels observed among participants with lower GFR) before higher levels of serum parathyroid hormone and phosphorus were observed. Plasma fibroblast growth factor 23 levels were 34% higher in participants with glomerular disease than in participants with nonglomerular disease, despite similar GFR. Serum phosphorus levels, adjusted for age, were significantly lower at GFR of 60-69 ml/min per 1.73 m(2) than higher GFR, but thereafter they became higher in parallel with fibroblast growth factor 23 as GFR declined. Serum 1,25-dihyroxyvitamin D concentrations were lower in those participants with low GFR values, high fibroblast growth factor 23 levels, 25-hydroxyvitamin D deficiency, and proteinuria. Secondary hyperparathyroidism was present in 55% of participants with GFR<50 ml/min per 1.73 m(2). CONCLUSION: In children with predialysis CKD, high plasma fibroblast growth factor 23 is the earliest detectable abnormality in mineral metabolism, and levels are highest in glomerular diseases.