Journal Article

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 and Rukshana Shroff

in Nephrology Dialysis Transplantation

Published on behalf of European Renal Association - European Dialysis and Transplant Assoc

Volume 28, issue 1, pages 153-161
Published in print January 2013 | ISSN: 0931-0509
Published online November 2012 | e-ISSN: 1460-2385 | DOI: http://dx.doi.org/10.1093/ndt/gfs411
Fibroblast growth factor 23 and soluble klotho in children with chronic kidney disease

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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 m2, 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)2D] 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.

Keywords: children; chronic kidney disease; FGF23; paediatric nephrology; s-klotho

Journal Article.  5497 words.  Illustrated.

Subjects: Nephrology

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