Investigating FGF-23 concentrations and its relationship with declining renal function in paediatric patients with pre-dialysis CKD Stages 3-5

Background
The aims of our study were to investigate (i) the prevalence of elevated fibroblast growth factor-23 (FGF-23), (ii) the relationship between FGF-23 concentrations and level of renal dysfunction and (iii) the main determinants of elevation of FGF-23 concentration in children with pre-dialysis chronic kidney disease (CKD) Stages 35.

Methods
In this single-centre prospective observational study, 71 children with pre-dialysis CKD Stages 35, aged 11.9 3.1 years, had FGF-23 levels measured. Anthropometry and routine laboratory investigations were measured.

Results
Fourteen (19.7) patients had normal FGF-23 concentrations defined as 50 ng/L. FGF-23 [median (interquartile range)] concentrations were 78.7 (55.6137.6) ng/L and following log transformation normalized data with log FGF-23 [mean (SD)] values of 1.96 0.4 ng/L. Log FGF-23 concentrations had a negative reciprocal relationship with estimated glomerular filtration rate (eGFR) (P 0.0001) and 1,25 vitamin D3 levels (P 0.01) and a positive relationship with phosphate (P 0.03) and percent fractional excretion of phosphate (P 0.01) but not with log-intact parathyroid hormone (PTH) (P 0.22). Multiple linear regression demonstrated a strong relationship between log FGF-23 and eGFR only.

Conclusions
Elevated FGF-23 concentrations were observed in the majority of a carefully managed cohort of children with non-dialysis CKD with a dominant effect on FGF-23 concentrations with glomerular filtration rate (GFR). These data allow the potential confounding effects of PTH and phosphate elevation with declining GFR to be removed, leaving a clearer picture of the FGF-23GFR relationship.