Supplementary Material for: Methodology and baseline data of a comparative exploratory double-blinded randomized study of intravenous iron on fibroblast growth factor 23 and phosphate in chronic kidney disease

Modern intravenous iron compounds (e.g., ferric carboxymaltose (FCM) and ferric derisomaltose (FDI)) are utilized in the treatment of iron deficiency anemia in non-dialysis dependent chronic kidney disease (ND-CKD). Product-specific alterations in the metabolism of fibroblast growth factor 23 (FGF-23) leading to hypophosphatemia have been described for certain intravenous iron compounds, such as FCM, with potential effects on bone and cardiovascular health and quality of life. No prior head-to-head comparison between FCM and FDI exists in ND-CKD. This single-center exploratory double-blinded randomized controlled trial primarily aimed to investigate the differential impact of FCM and FDI on FGF-23 and phosphate in patients with iron deficiency +/- anemia and ND-CKD (stages 3a-5 – serum ferritin < 200 μg/L or serum ferritin 200-299 μg/L and transferrin saturation < 20%). Patients were randomized (1:1) to receive either FCM or FDI over two infusions (one-month apart). Follow-up was three months. Measurements of serum intact FGF-23, phosphate, vitamin D metabolites, parathyroid hormone other bone metabolism, cardiovascular and quality of life markers were monitored. 168 patients were pre-screened. Thirty-five patients were screened; 26 patients were randomized. The mean (standard deviation) age was 67.9 (12.4) and 17 participants were male. Most participants had stage 4 CKD (median (interquartile range) eGFR: 18.0 (11.3) ml/min/1.73 m2). A higher than normal median (interquartile range) level of intact FGF-23 (212.1 (116.4) pg/ml) was noted. Serum phosphate was within normal range, while parathyroid hormone was higher and 1,25 (OH)2 vitamin D lower than the normal range. The “Iron and Phosphaturia – ExplorIRON-CKD” trial will provide important information regarding the differential effect of intravenous iron products in terms of FGF-23, phosphate and other markers of bone and cardiovascular metabolism, alongside patient reported outcome measures in patients with ND-CKD.