Disordered FGF23 and mineral metabolism in children with CKD
Anthony A Portale1, Myles Wolf, Harald Jüppner
1Department of Pediatrics, University of California, San Francisco, California;, †Department of Medicine and, §Department of Epidemiology and Public Health, University of Miami Miller School of Medicine, Miami, Florida;, ‡Department of Pediatrics, Harvard Medical School, Boston, Massachusetts;, ‖Department of Pediatrics, Weill Cornell Medical College, New York, New York;, ¶Department of Pediatrics, University of California, Los Angeles, California;, *Department of Pediatrics, University of Rochester School of Medicine, Rochester, New York;, ††Department of Pediatrics, University of Pennsylvania, Philadelphia, Pennsylvania, ‡‡Department of Pediatrics, University of Missouri-Kansas City School of Medicine, Kansas City, Missouri.
Insights
In children with predialysis chronic kidney disease (CKD), high fibroblast growth factor 23 (FGF23) is an early sign of mineral metabolism issues, particularly in glomerular diseases.
Area of Science:
- Pediatric Nephrology
- Mineral and Bone Metabolism
- Chronic Kidney Disease (CKD) Research
Background:
- Limited data exists on fibroblast growth factor 23 (FGF23) excess and 1,25-dihydroxyvitamin D deficiency in predialysis pediatric CKD.
- Understanding these derangements is crucial for managing CKD progression and complications in children.
Purpose of the Study:
- To characterize FGF23 and 1,25-dihydroxyvitamin D levels in children with predialysis CKD.
- To investigate the relationship between FGF23, 1,25-dihydroxyvitamin D, GFR, and secondary hyperparathyroidism.
- To identify determinants of these mineral metabolism abnormalities across CKD stages.
Main Methods:
- Analysis of plasma FGF23 and mineral metabolism markers in 464 children (ages 1-16) with predialysis CKD.
- GFR assessment using iohexol clearance or validated estimating equations.
- Categorization of participants by CKD stage and GFR (10-ml/min intervals).
Main Results:
- Elevated FGF23 (above normal range) was found in 67% of participants, increasing as GFR declined.
- FGF23 levels were higher in glomerular disease versus nonglomerular disease, independent of GFR.
- 1,25-dihydroxyvitamin D deficiency correlated with low GFR, high FGF23, vitamin D deficiency, and proteinuria. Secondary hyperparathyroidism affected 55% of those with GFR<50 ml/min/1.73 m(2).
Conclusions:
- Elevated plasma FGF23 is the earliest indicator of mineral metabolism disturbance in children with predialysis CKD.
- Glomerular diseases are associated with the highest FGF23 levels in this pediatric cohort.
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.
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