Differential Impacts of Intravenous Iron Administration and Iron-Containing Phosphate Binders on Serum Intact Fibroblast Growth Factor 23 Levels

Honda, Hirokazu; Tanaka, Kenji; Michihata, Tetsuo; Shibagaki, Keigo; Yuza, Toshitaka; Hirao, Keiichi; Tomosugi, Naohisa; Shibata, Takanori

doi:10.1159/000496640

Cited by 5 publications

(3 citation statements)

References 23 publications

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“…However, a stronger association was identified between acute reactions and the risk of infectious disease in patients being treated with intravenous iron than that in those being treated with oral iron [30]. Furthermore, it has been reported that intravenous iron administration increases the circulating FGF23 concentration, whereas oral iron reduces FGF23 in these patients [15,32]. Therefore, oral iron is used in preference in our hospital and only one patient had received intravenous iron supplementation at baseline in the present study.…”

Section: Discussionmentioning

confidence: 65%

Iron, coronary artery calcification, and mortality in patients undergoing hemodialysis

Mizuiri¹,

Nishizawa²,

Doi

et al. 2021

Renal Failure

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Objective: A high coronary artery calcification score (CACS) may be associated with high mortality in patients undergoing hemodialysis (HD). Recently, effects of iron on vascular smooth muscle cell calcification have been described. We aimed to investigate the relationships between iron, CACS, and mortality in HD patients. Methods: We studied 173 consecutive patients who were undergoing maintenance HD. Laboratory data and Agatston's CACS were obtained at baseline for two groups of patients: those with CACS !400 (n ¼ 109) and those with CACS <400 (n ¼ 64). Logistic regression analyses for CACS !400 and Cox proportional hazard analyses for mortality were conducted. Results: The median (interquartile range) age and duration of dialysis of the participants were 67 (60-75) years and 73 (37-138) months, respectively. Serum iron (Fe) and transferrin saturation (TSAT) levels were significantly lower in participants with CACS !400 than in those with CACS <400, although the serum ferritin concentration did not differ between the groups. TSAT !21% was significantly associated with CACS !400 (odds ratio 0.46, p<0.05). TSAT !17%, Fe !63 mg/ dL, and ferritin !200 ng/mL appear to protect against 5-year all-cause mortality in HD patients, independent of conventional risk factors of all-cause mortality (p < 0.05). Conclusion:We have identified associations between iron, CACS, and mortality in HD patients. Lower TSAT was found to be an independent predictor of CACS !400, and iron deficiency (low TSAT, iron, or ferritin) was a significant predictor of 5-year all-cause mortality in HD patients.

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Section: Discussionmentioning

confidence: 65%

Iron, coronary artery calcification, and mortality in patients undergoing hemodialysis

Mizuiri¹,

Nishizawa²,

Doi

et al. 2021

Renal Failure

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“…The ExplorIRON-CKD trial is the first exploratory comparative trial including two modern intravenous irons, FCM and FDI, in the ND-CKD population studying a potential hypophosphatemic effect. Previous studies in patients with ND-CKD and on hemodialysis incorporating oral and intravenous iron have had contradictory results [20‒25, 41, 51, 52], especially in terms of FGF-23 metabolism, where the changes in FGF-23 did not necessarily translate to clinically significant hypophosphatemia even when a decrease in phosphate was seen. The measure of iFGF-23 as opposed to cFGF-23 can provide further information on the action of bioactive FGF-23 in relation to any effects.…”

Section: Discussionmentioning

confidence: 99%

“…Chronic kidney disease represents a state of increased FGF-23 concentration, which potentially is key in the development of CKD mineral bone disorder [19]. The exact nature of alterations in metabolism of FGF-23 in CKD is poorly understood, and therefore it is difficult to explain the discrepancies that exist between FGF-23 concentrations (iFGF-23 and cFGF-23) following intravenous iron administration in hemodialysis-dependent patients [20][21][22][23][24]. Nonetheless, a key study (n = 65) prospectively examined the effects of 1,000 mg of FCM on FGF-23 in patients with normal renal function, pregnant individuals, and patients with ND-CKD [25].…”

Section: Introductionmentioning

confidence: 99%

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

Kassianides

Bhandari

2023

Kidney Blood Press Res

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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-blind 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 (1 month apart). Follow-up was 3 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 prescreened. Thirty-five patients were screened; 26 patients were randomized. The mean (standard deviation) age was 67.9 (12.4) years and 17 participants were male. Most participants had stage 4 CKD (median [interquartile range] estimated glomerular filtration rate [eGFR]: 18.0 [11.3] mL/min/1.73 m<sup>2</sup>). 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)<sub>2</sub> 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.

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The Effect of Iron Supplementation on FGF23 in Chronic Kidney Disease Patients: a Systematic Review and Time-Response Meta-Analysis

Abu‐Zaid

Magzoub

Aldehami

et al. 2021

Biol Trace Elem Res

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Differential Impacts of Intravenous Iron Administration and Iron-Containing Phosphate Binders on Serum Intact Fibroblast Growth Factor 23 Levels

Cited by 5 publications

References 23 publications

Iron, coronary artery calcification, and mortality in patients undergoing hemodialysis

Iron, coronary artery calcification, and mortality in patients undergoing hemodialysis

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

The Effect of Iron Supplementation on FGF23 in Chronic Kidney Disease Patients: a Systematic Review and Time-Response Meta-Analysis

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