Fibroblast growth factor 23 and soluble klotho in children with chronic kidney disease

Mandy Wan, Colette Smith, Vanita Shah, Ambrose Gullet, David Wells, Lesley Rees, Rukshana Shroff

Research output: Contribution to journalArticlepeer-review

71 Citations (Scopus)

Abstract

BACKGROUND: Fibroblast growth factor 23 (FGF23), a bone-derived phosphaturic hormone, is elevated in chronic kidney disease (CKD). There are scarce data on the levels of its essential co-receptor klotho, and longitudinal changes in FGF23 levels are also unknown.

METHODS: We examined FGF23 and soluble klotho (s-klotho) levels over 1 year in 154 children with CKD Stages 1-5 (CKD1-5), were on dialysis or who have received a transplantation.

RESULTS: In children with CKD1-5 and who were receiving dialysis, FGF23 correlated inversely with the estimated glomerular filtration rate (eGFR) (P < 0.001), whereas a decrease in s-klotho was observed with a lower eGFR (P = 0.01). There was no correlation between FGF23 and serum phosphate (P) or parathyroid hormone (PTH) in our cohort wherein 89 and 66%, respectively, had normal levels. FGF23 increased by 6-fold over a 12-month period in children with eGFR of 15-29 mL/min/1.73 m(2), with an overall 5% annual increase in the CKD1-5 and dialysis cohort. High FGF23 levels were seen with high calcium (Ca) levels (P < 0.001). FGF23 levels were high when 25-hydroxyvitamin D [25(OH)D] and 1,25-dihydroxyvitamin D [1,25(OH)(2)D] were deficient (P = 0.05 and P < 0.001, respectively). s-klotho levels correlated positively with 25(OH)D (P < 0.001) and negatively with PTH (P = 0.04) and age (P = 0.03). Multivariate regression analysis demonstrated a strong relationship between FGF23 and eGFR, whereas the association between s-klotho and eGFR as observed in univariate analysis was lost following the adjustment of confounders. In transplanted patients, FGF23 correlated with eGFR (P = 0.02) and 25(OH)D (P = 0.05).

CONCLUSIONS: This study shows increasing FGF23 and reduced s-klotho levels with progressive renal failure even in a population of children with well-controlled P levels. Novel associations between FGF23 and serum Ca as well as 25(OH)D warrant further investigation.

Original languageEnglish
Pages (from-to)153-61
Number of pages9
JournalNephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association
Volume28
Issue number1
DOIs
Publication statusPublished - Jan 2013

Keywords

  • Adolescent
  • Child
  • Child, Preschool
  • Female
  • Fibroblast Growth Factor-23
  • Fibroblast Growth Factors/blood
  • Glomerular Filtration Rate
  • Glucuronidase/blood
  • Humans
  • Kidney Transplantation
  • Klotho Proteins
  • Longitudinal Studies
  • Male
  • Renal Dialysis
  • Renal Insufficiency, Chronic/blood

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