Association of fibroblast growth factor 23 and α-klotho in hemodialysis patients during administration of ferric citrate hydrate: post hoc analysis of ASTRIO study

BMC Nephrology

Masafumi Fukagawa¹  Hideki Hirakata²  Keitaro Yokoyama³  Kyoko Ito⁴  Masaaki Nakayama⁵ 

[1] Division of Nephrology, Endocrinology and Metabolism, Tokai University School of Medicine, Isehara, Japan;Fukuoka Renal Clinic, Fukuoka, Japan;Health Care Center, Harumi Toriton Clinic, The Jikei University Hospital, 1-8-8 Harumi, Chuo-ku, 104-0053, Tokyo, Japan;Medical Affairs Department, Torii Pharmaceutical Co. Ltd., Tokyo, Japan;St. Luke’s International University, St. Luke’s International Hospital, Tokyo, Japan;

关键词: ASTRIO study;    Ferric citrate hydrate;    FGF23;    α-Klotho;    Hemodialysis;    iron-based phosphate binder;   

DOI  :  10.1186/s12882-021-02575-9

来源: Springer

【 摘 要 】

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).

【 授权许可】

CC BY