Effects of intravenous iron on fibroblast growth factor 23 (FGF23) in haemodialysis patients: a randomized controlled trial

Abstract

Background: Intravenous iron affects serum levels of intact fibroblast growth factor-23 (iFGF23) and its cleavage product c-terminal FGF23 (cFGF23) in iron-deficient people with normal renal function. We hypothesized that intravenous iron modulates iFGF23 and cFGF23 in haemodialysis patients differently according to the type of iron used.

Methods: Prevalent, stable haemodialysis patients requiring protocol-based intravenous iron therapy were randomized to a single 200 mg dose of either ferric carboxymaltose (FCM) or iron sucrose (IS). The primary outcome was change in iFGF23 and cFGF23 from pre-infusion to Day 2 post-infusion. Serum hepcidin, ferritin and phosphate were also measured. Pair-wise comparisons utilised the Wilcoxon rank sum test; linear mixed models with an interaction term for treatment and time evaluated between-group effects.

Results: Forty-two participants completed the study. In those randomized to FCM (n = 22), median (interquartile range) values pre-infusion and Day 2, respectively, were 843 pg/mL (313-1922) and 576 pg/mL (356-1296, p = 0.05) for iFGF23, 704RU/mL (475-1204) and 813RU/mL (267-1156, p = 0.04) for cFGF23, and 1.53 mmol/L (1.14-1.71) and 1.37 (1.05-1.67, p = 0.03) for phosphate. These parameters did not change following IS. Both serum ferritin (p < 0.001) and hepcidin (p < 0.001) increased in both groups, and the increase in hepcidin was greater in the FCM group (p = 0.03 for between-group difference).

Conclusions: Contrary to iron-deficient people with normal renal function, haemodialysis patients given protocol-driven intravenous FCM demonstrated a fall in iFGF23 and a rise in cFGF23, changes not evident with IS. This suggests a differential effect of intravenous iron treatment according to both formulation and renal function.

Trial registration: Australian and New Zealand Clinical Trials Register ACTRN12614000548639 . Registered 22 May 2014 (retrospectively registered).

Keywords: Fibroblast growth factor-23; Haemodialysis; Hepcidin; Iron infusion; Randomized controlled trial.

Fig. 1

CONSORT Flow diagram of patient enrolment

Fig. 2

Median (interquartile range) levels over the course of the study of iFGF23 (pg/mL), cFGF23 (RU/mL) and phosphate (mmol/L) in participants treated with iron sucrose (left panels) and ferric carboxymaltose (right panels)

Fig. 3

Median (interquartile range) levels over the course of the study of serum hepcidin (ng/mL), ferritin (μg/L) and haemoglobin (g/L) in participants treated with iron sucrose (left panels) and ferric carboxymaltose (right panels)

Fig. 4

Median levels of cFGF23 over time in participants with low (<500 mL) daily urine output (left panel) and higher (≥500 mL) daily urine output (right panel)