Oral iron supplementation with sodium ferrous citrate reduces the serum intact and c‐terminal fibroblast growth factor 23 levels of maintenance haemodialysis patients
Recently, an animal study suggested that iron deficiency stimulates FGF23 transcription in osteocytes.6 Furthermore, it was reported that the short‐term use of iron‐based phosphate binders, such as ferric citrate and sucroferric oxyhydroxide, replenished the iron stores and reduced the serum phosphate and FGF23 levels of patients with CKD and HD patients with iron deficiency.7 Both ferric citrate and sucroferric oxyhydroxide contain ferric iron (Fe3+), whereas sodium ferrous citrate (Ferromia; Eisai Co., Ltd. Tokyo, Japan) contains ferrous iron (Fe2+). The package insert for Ferromia is shown in the supplemental file. In general, ferric iron (Fe3+) results in lower iron absorption than ferrous iron (Fe2+),11 and ferric iron (Fe3+) retains its phosphate binding capacity.11 The co‐administration of antacid and iron tablets results in a marked reduction in iron absorption, and so sodium ferrous citrate (C12H10FeNa4O14; Fe2+) was developed to increase patients’ serum iron levels in a manner that was not affected by gastric acid secretion (see the supplemental file). It was reported that the increase in the serum iron concentration brought about by the administration of sodium ferrous citrate was enhanced by the addition of ascorbic acid, whereas the increase associated with the administration of ferrous sulfate (FeSO4•xH2O; Fe2+) was not affected.12
The 2012 Kidney Disease Improving Global Outcomes (KDIGO) guidelines for anaemia in CKD recommend that iron supplements should be administered to patients that exhibit serum transferrin saturation (TSAT) values of ≤30% and serum ferritin concentrations of ≤500 ng/mL.13 However, the Japanese Society for Dialysis Therapy (JSDT) guidelines state that iron should be given to HD patients with TSAT values of ≤20% and serum ferritin levels of ≤100 ng/mL.14 According to data for 2012–2014 from the United States (US) RENAL DATA STSTEM (https://www.usrds. org/2015/view/v2_03.aspx?zoom_), 13% of US HD patients had TSAT values of <20%, and 12% had ferritin concentrations of ≤200 ng/mL. In addition, data for 2012 from the UK renal registry indicated that the median ferritin concentration of UK HD patients was 431 µg/L.15 Furthermore, a statistical survey conducted by the JSDT at the end of 2012 revealed that 36.2% of Japanese HD patients had TSAT values of <20%, and 58.3% had ferritin concentrations of <100 ng/mL.16 Thus, iron deficiency is relatively common in Japanese HD patients.
The aim of this study was to determine whether oral ferrous iron (Fe2+) supplementation with sodium ferrous citrate reduces the serum FGF23 levels of maintenance HD (MHD) patients with iron deficiency in the same way as oral ferric iron (Fe3+).