Administration of Ferric Citrate Hydrate Decreases Circulating FGF23 Levels Independently of Serum Phosphate Levels in Hemodialysis Patients with Iron Deficiency

Iguchi, Akira; Kazama, Junichiro James; Yamamoto, Shuichi; Yoshita, Kazuhiro; Watanabe, Yasuo; Iino, Noriaki; Narita, Ichiei

doi:10.1159/000440968

Cited by 40 publications

(36 citation statements)

References 32 publications

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“…In the present study, however, we could not evaluate whether ferric citrate modulated FGF23 degradation because C-terminal FGF23 levels were not measured. However, it has been reported that the ratio of intact to C-terminal FGF23, which indicates the amount of degradation of full-length FGF23, did not change following ferric citrate administration in hemodialysis patients, suggesting that ferric citrate has a relatively small influence on FGF23 degradation [16]. In the present study, switching from lanthanum carbonate to ferric citrate hydrate reduced FGF23 levels in patients on hemodialysis.…”

Section: Discussioncontrasting

confidence: 57%

“…Moreover, intravenous saccharated ferric oxide induced further increase in elevated FGF23 levels in hemodialysis patients [31]. Conversely, oral ferric citrate administration decreased serum intact FGF23 levels and increased iPTH levels in both hemodialysis-dependent and non-hemodialysis-dependent CKD patients [10, 16]. Furthermore, a study by David et al [34] on the chronic effects of iron supplementation showed that the role of iron on the degradation of circulating FGF23 might differ between the acute and the chronic phase of iron-deficiency anemia.…”

Section: Discussionmentioning

confidence: 99%

“…Continuous variables were compared using the Students t test or the Mann-Whitney U test, and categorical variables were compared using the χ 2 test or Fisher’s exact test. The sample size required to achieve 80% power was calculated assuming an effect size of a 30% difference in the mean percent change in FGF23 levels from baseline between the groups with an SD of 40%, based on a previous trial [9, 16]. This yielded a 2-sided significance level of 0.05, and an estimated number of evaluable patients of 44 (22 per group).…”

Section: Methodsmentioning

confidence: 99%

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Ferric Citrate Decreases Fibroblast Growth Factor 23 and Improves Erythropoietin Responsiveness in Hemodialysis Patients

et al. 2018

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Background: Serum phosphate and vitamin D receptor activator regulate fibroblast growth factor 23 (FGF23), and iron may modulate FGF23 metabolism. The aim of the present study was to elucidate the effects of ferric citrate hydrate and lanthanum carbohydrate on serum FGF23 levels in hemodialysis patients. Methods: This prospective, open-label, multicenter study enrolled 60 patients on hemodialysis treated with lanthanum carbonate. Patients were randomly assigned to 2 groups: those switching from lanthanum carbonate to ferric citrate hydrate (ferric citrate group, n = 30) or those continuing lanthanum carbonate (control group, n = 30). Patients were monitored for 24 weeks. Endpoints included changes in FGF23, phosphate, and the dose of erythropoiesis stimulating agent (ESA), erythropoietin responsiveness index (ERI), and adverse events. Results: FGF-23 levels were significantly lower in the ferric citrate group compared with the levels in the control group (change from baseline –6,160 vs. –1,118 pg/mL; p = 0.026). There were no significant changes in serum calcium, phosphate, and intact parathyroid hormone levels in either group. The ferric citrate group had significantly increased serum iron, ferritin, and transferrin saturation. Hemoglobin levels were significantly elevated, and the dose of ESA was significantly decreased in the ferric citrate group but not in the control group. ERI and the dose of intravenous saccharated ferric oxide were significantly lower in the ferric citrate group compared with those of the control group (p = 0.015 and p = 0.002). Conclusion: In patients on hemodialysis, 24-week treatment with ferric citrate hydrate resulted in significant reduction in FGF23 and ERI independently of serum phosphate level.

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Section: Discussioncontrasting

confidence: 57%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Ferric Citrate Decreases Fibroblast Growth Factor 23 and Improves Erythropoietin Responsiveness in Hemodialysis Patients

et al. 2018

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“…[153] circulating FGF23 levels independently of serum phosphate concentrations in hemodialysis patients [154]. In concert, an appropriate level of iron status is required to suppress serum FGF23 levels and potentially to prevent the development of cardiac hypertrophy.…”

Section: Non-iron Depleted Uremic Ratsmentioning

confidence: 99%

Cardiac hypertrophy in chronic kidney disease—role of Aldosterone and FGF23

Hayashi

Suzuki²,

Sakamaki

et al. 2018

Ren Replace Ther

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Cardiac hypertrophy is a life-threatening disorder and is frequently observed in patients with chronic kidney disease (CKD). Much attention has been focused on the derangement in hormonal factors, including aldosterone and FGF23, as novel causes of cardiac hypertrophy in CKD. Plasma aldosterone concentrations are elevated as renal function declines. Although aldosterone antagonists are available for the treatment of hypertension with cardiac hypertrophy, concern remains regarding the possible occurrence of serious hyperkalemia. Alternatively, certain types of calcium channel blockers suppress aldosterone synthesis or exert blocking action for mineralocorticoid receptors and could halt the progression of cardiac dysfunction. Recently, FGF23 is shown to be elevated as CKD progresses and may be responsible for the development of cardiac hypertrophy and heart failure. Furthermore, FGF23 not only inhibits the renal expression of angiotensin converting enzyme 2 but also enhances renin gene transcription, both of which could accelerate renin-angiotensin-aldosterone system. Although the increase in serum phosphate concentrations is a pivotal stimulus for FGF23 production, recent studies suggest that reduced iron status and elevated aldosterone levels, frequently seen in patients with CKD or on dialysis, might also contribute to the elevation in serum FGF23 levels. Conversely, phosphate binders and appropriate iron status could reduce serum FGF23, potentially leading to the alleviation of cardiac hypertrophy and heart failure. In conclusion, novel therapeutic strategies associated with aldosterone and FGF23 may confer a benefit in the management of cardiac disorders in CKD.

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“…It is used to replete iron stores in iron deficiency anemia and reduces the requirement of intravenous iron and erythropoiesis stimulating agents (ESA) [4] and thus, ferric citrate is a dual-purpose therapeutic agent for dialysis patients. Recent studies reported that administration of ferric citrate led to decreased levels of serum fibroblast growth factor 23 (FGF23) independent of phosphate [3,5], reduced the cost of anemia-management therapies [6], and was associated with fewer hospitalizations and associated costs [7].…”

Section: Introductionmentioning

confidence: 99%

Long-term iron accumulation in dialysis patients treated with ferric citrate hydrate: a single-center, 80-week retrospective study in Japan

et al. 2017

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Background: Ferric citrate hydrate (FCH), an iron-based phosphate binder, affects mineral and iron metabolism in patients with chronic kidney disease (CKD). The long-term impact of FCH on iron overload is unknown. With this study, we investigated whether the type of dialysis is associated with FCH-related iron accumulation. Methods: This single-center, retrospectively registered, cohort study was performed in Kariya-Toyota General Hospital, Japan, among outpatients undergoing maintenance hemodialysis (HD) or peritoneal dialysis (PD) between July 2014 and January 2017. It included 136 subjects receiving FCH treatment (104 HD patients and 32 PD patients). Their iron metabolism parameters and FCH-associated adverse events were assessed over 80 weeks. Results: In both groups, the weekly darbepoetin alpha dose and erythropoiesis resistance index declined significantly by 16 weeks, although mean hemoglobin concentrations remained stable (10-11 g/dL), and transferrin saturation peaked at 24 weeks. The difference in the weekly darbepoetin alpha dose for HD and PD patients was 16.5 and 12. 0 μg/week, respectively, (P < 0.01). Increases in iron stores were different between the two groups. Peak mean increase in serum ferritin levels (169.0 vs. 63.0 ng/mL, respectively; P = 0.001) in PD patients at 40 weeks was significantly earlier than that in HD patients. The adverse events observed suggest that FCH treatment was more likely to be discontinued within the first 16 weeks due to hemoglobin overshooting in HD patients and after 40 weeks due to ferritin overload in PD patients. Conclusions: Oral iron supplementation with FCH was successful in all dialysis patients. However, the type of dialysis is a major factor associated with iron accumulation during long-term FCH treatment and more likely to occur in PD patients not experiencing regular, dialysis-associated iron loss. Therefore, the method of dialysis should be taken into consideration when evaluating iron stores of patients with CKD to determine the appropriate starting dose of FCH.

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Administration of Ferric Citrate Hydrate Decreases Circulating FGF23 Levels Independently of Serum Phosphate Levels in Hemodialysis Patients with Iron Deficiency

Cited by 40 publications

References 32 publications

Ferric Citrate Decreases Fibroblast Growth Factor 23 and Improves Erythropoietin Responsiveness in Hemodialysis Patients

Ferric Citrate Decreases Fibroblast Growth Factor 23 and Improves Erythropoietin Responsiveness in Hemodialysis Patients

Cardiac hypertrophy in chronic kidney disease—role of Aldosterone and FGF23

Long-term iron accumulation in dialysis patients treated with ferric citrate hydrate: a single-center, 80-week retrospective study in Japan

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