The effects of iron on FGF23-mediated Ca-P metabolism in CKD patients

Fibroblast growth factor 23 (FGF23) is an important counterregulatory hormone for phosphate homeostasis. Since it has been reported that iron administration induces hypophosphatemic osteomalacia by triggering FGF23 synthesis, we hypothesized that iron administration might lead to a further increase in FGF23, resulting in alterations to Ca-P metabolism in a stage 5 CKD population.

This cross-sectional study was performed in a single center, and involved 73 hemodialysis patients (47.7 ± 15.74 years old, 68.5% men), 29 peritoneal dialysis patients (44.55 ± 15.05 years old, 62.1% men), and 55 healthy (43.57 ± 14.36 years old, 55.6% men) subjects. The dialysis group was subcategorized according to iron therapy administration into users and nonusers.

The median iFGF23 level was significantly higher in the dialysis population than in the healthy controls [88.050 (25.2-1038.3) pg/ml versus 46.95 (2.4-356) pg/ml (p < 0.001)]. In the dialysis population, a significantly lower median iFGF23 level was observed in iron therapy users than in nonusers [87.6 (25.2-1038.3) versus 119 (51.6-1031); respectively, p = 0.045]. A significant negative association between iron administration and iFGF23 level was revealed by both univariate (r = -0.237, p = 0.016) and multivariate (β = -0.221, p = 0.032) analysis. No association was found between iFGF23 and serum ferritin and iron levels. Also, there was no association between iron therapy and serum phosphate level.

In contrast to what is seen for the general population, this study showed that there was a negative relationship between iron administration and serum iFGF23 level in a dialysis population. We can therefore conclude that if high levels of FGF23 are harmful, iron therapy may have a beneficial effect on bone metabolism by reducing FGF23 levels in a dialysis population.