Abstract
BackgroundFibroblast growth factor-23 (FGF23) and α-klotho are associated with anemia in patients with chronic kidney disease. In this post hoc analysis of the ASTRIO study (UMIN000019176), we investigated the relationship between FGF23 and α-klotho during treatment with an iron-based phosphate binder, ferric citrate hydrate (FC), compared with non-iron-based phosphate binders in hemodialysis (HD) patients. We examined the effect of iron absorption by FC on the relationship between FGF23 and α-klotho. There have been few clinical studies evaluating these biomarkers simultaneously in HD patients.MethodsThe ASTRIO study was a 24-week, randomized, open-label, multicenter trial. HD patients taking non-iron-based phosphate binder(s) were randomized at a 1:1 ratio to continue other binder(s) (control group) or switch to FC (FC group). Serum phosphate (P) and hemoglobin (Hb) were maintained within 3.5–6.0 mg/dL and 10–12 g/dL, respectively. Plasma levels of intact FGF23 (i-FGF23), C-terminal FGF23 (c-FGF23), and α-klotho were measured, as were iron-related parameters. Association analyses of FGF23 and α-klotho were conducted.ResultsPatients were randomized to FC (n = 48) and control (n = 45) groups. Serum ferritin significantly increased from baseline to end-of-treatment (EOT) in the FC group, compared with the control group (adjusted mean difference [95% confidence interval]: 79.5 [44.7, 114.4] ng/mL; p < 0.001). The mean change from baseline to EOT in c-FGF23 was significantly different between the FC and control groups (mean ± standard deviation (SD): − 0.2 ± 0.8 loge pg/mL vs. 0.2 ± 0.8 loge pg/mL, respectively; p = 0.04). The mean change from baseline to EOT in i-FGF23 and α-klotho were not significantly different between the FC and control groups (mean ± SD: − 0.1 ± 0.8 loge pg/mL vs. 0.1 ± 0.9 loge pg/mL; p = 0.33, and 2.0 ± 91.5 pg/mL vs. − 8.9 ± 145.3; p = 0.58, respectively). However, both forms of FGF23 and α-klotho were not significantly associated with each other in both groups.ConclusionsIron absorbed via FC administration in HD patients did not influence the correlation relationship between plasma levels of FGF23 and α-klotho under the condition of serum P and Hb were maintained.Trial registrationASTRIO study (UMIN000019176, registered at UMIN Clinical Trials Registry on October 1, 2015).
Highlights
Fibroblast growth factor-23 (FGF23) and α-klotho are associated with anemia in patients with chronic kidney disease
The results suggested that iron from ferric citrate hydrate (FC) was partially absorbed and contributed to the reduced dose of erythropoiesisstimulating agent (ESA), while improving C-terminal FGF23 (c-FGF23) levels
We investigated whether iron absorbed via FC administration could influence the relationship between FGF23 and α-klotho by using data obtained from the ASTRIO study [21]
Summary
Fibroblast growth factor-23 (FGF23) and α-klotho are associated with anemia in patients with chronic kidney disease. In this post hoc analysis of the ASTRIO study (UMIN000019176), we investigated the relationship between FGF23 and α-klotho during treatment with an iron-based phosphate binder, ferric citrate hydrate (FC), compared with non-iron-based phosphate binders in hemodialysis (HD) patients. FGF23 is an endocrine hormone expressed in bone [4,5,6] that plays an important role in the maintenance of phosphate and calcium balance by binding to FGF receptors expressed in the kidney [7] It regulates the secretion of parathyroid hormone to ensure a normal level of serum calcium. Iron homeostasis, inflammation, and erythropoiesis have been associated with FGF23 regulation [6]
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