The association of circulating ferritin with serum concentrations of fibroblast growth factor-23 measured by three commercial assays

Background: The measurement of the serum concentration of fibroblast growth factor-23 (FGF-23) is beginning to be used as a diagnostic tool in renal phosphate wasting disorders. Having observed an increased serum FGF-23 in three subjects with low circulating ferritin concentrations we investigated the association between low ferritin and raised serum FGF-23.

Methods: We measured FGF-23 in 150 random anonymized serum samples with ferritin concentrations between <5 and 50 µg/L using three commercially available enzyme-linked immunosorbent assay (ELISA) kits. One kit, Human FGF-23[C-term] (Immutopics Inc, USA) measures total FGF-23 whereas the other two kits, Immutopics intact and FGF-23 ELISA (Kainos, Japan) are reported to measure only the biologically active intact molecule.

Results: We have detected a significant inverse correlation of -0.565 (P<0.0001) between serum ferritin when <50 µg/L and FGF-23 using the C-terminal assay. This relationship is also shown with the Immutopics intact assay but is not demonstrated with the Kainos intact assay.

Conclusion: The measurement of FGF-23 by both Immutopics assays is altered in the presence of low circulating concentrations of serum ferritin whereas with the Kainos intact assay this effect was not demonstrated. Serum ferritin should be measured when an elevated FGF-23 is obtained using the Immutopics C-terminal or intact FGF-23 assay to prevent misdiagnosis of the cause of this abnormality.