Disordered FGF23 and mineral metabolism in children with CKD

Anthony A. Portale, Myles Wolf, Harald Jüppner, Shari Messinger, Juhi Kumar, Katherine Wesseling-Perry, George J. Schwartz, Susan L. Furth, Bradley A. Warady, Isidro B. Salusky

Research output: Contribution to journalArticle

Abstract

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 m2 (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 m2 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 GFR2. 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.

Original languageEnglish (US)
Pages (from-to)344-353
Number of pages10
JournalClinical Journal of the American Society of Nephrology
Volume9
Issue number2
DOIs
StatePublished - 2014
Externally publishedYes

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Minerals
Fibroblast Growth Factor 1
Secondary Hyperparathyroidism
Serum
Chronic Renal Insufficiency
Phosphorus
Iohexol
Cystatin C
fibroblast growth factor 23
Parathyroid Hormone
Proteinuria
Observational Studies
Creatinine
Reference Values
Cohort Studies

ASJC Scopus subject areas

  • Nephrology
  • Transplantation
  • Epidemiology
  • Critical Care and Intensive Care Medicine

Cite this

Portale, A. A., Wolf, M., Jüppner, H., Messinger, S., Kumar, J., Wesseling-Perry, K., ... Salusky, I. B. (2014). Disordered FGF23 and mineral metabolism in children with CKD. Clinical Journal of the American Society of Nephrology, 9(2), 344-353. https://doi.org/10.2215/CJN.05840513

Disordered FGF23 and mineral metabolism in children with CKD. / Portale, Anthony A.; Wolf, Myles; Jüppner, Harald; Messinger, Shari; Kumar, Juhi; Wesseling-Perry, Katherine; Schwartz, George J.; Furth, Susan L.; Warady, Bradley A.; Salusky, Isidro B.

In: Clinical Journal of the American Society of Nephrology, Vol. 9, No. 2, 2014, p. 344-353.

Research output: Contribution to journalArticle

Portale, AA, Wolf, M, Jüppner, H, Messinger, S, Kumar, J, Wesseling-Perry, K, Schwartz, GJ, Furth, SL, Warady, BA & Salusky, IB 2014, 'Disordered FGF23 and mineral metabolism in children with CKD', Clinical Journal of the American Society of Nephrology, vol. 9, no. 2, pp. 344-353. https://doi.org/10.2215/CJN.05840513
Portale AA, Wolf M, Jüppner H, Messinger S, Kumar J, Wesseling-Perry K et al. Disordered FGF23 and mineral metabolism in children with CKD. Clinical Journal of the American Society of Nephrology. 2014;9(2):344-353. https://doi.org/10.2215/CJN.05840513
Portale, Anthony A. ; Wolf, Myles ; Jüppner, Harald ; Messinger, Shari ; Kumar, Juhi ; Wesseling-Perry, Katherine ; Schwartz, George J. ; Furth, Susan L. ; Warady, Bradley A. ; Salusky, Isidro B. / Disordered FGF23 and mineral metabolism in children with CKD. In: Clinical Journal of the American Society of Nephrology. 2014 ; Vol. 9, No. 2. pp. 344-353.
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title = "Disordered FGF23 and mineral metabolism in children with CKD",
abstract = "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 m2 (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 m2 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 GFR2. 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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T1 - Disordered FGF23 and mineral metabolism in children with CKD

AU - Portale, Anthony A.

AU - Wolf, Myles

AU - Jüppner, Harald

AU - Messinger, Shari

AU - Kumar, Juhi

AU - Wesseling-Perry, Katherine

AU - Schwartz, George J.

AU - Furth, Susan L.

AU - Warady, Bradley A.

AU - Salusky, Isidro B.

PY - 2014

Y1 - 2014

N2 - 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 m2 (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 m2 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 GFR2. 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.

AB - 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 m2 (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 m2 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 GFR2. 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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