蔗糖化氧化铁可减弱聚乙二醇化促红素β在血液透析患者中引起的造血反应。

Saccharated ferric oxide attenuates haematopoietic response induced by epoetin beta pegol in patients undergoing haemodialysis.

机构信息

Internal Medicine (Nephrology and Dialysis), Hyogo College of Medicine, Mukogawa-cho, Nishinomiya City, Hyogo, 663-8501, Japan.

Department of Nephrology, Konan Medical Centre, 1-5-16 Kamokogahara, Higashinada-ku, Kobe, 658-0064, Japan.

出版信息

BMC Nephrol. 2021 Apr 8;22(1):124. doi: 10.1186/s12882-021-02320-2.

DOI:10.1186/s12882-021-02320-2

PMID:33832448

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8034147/

Abstract

BACKGROUND

Decreased erythropoietin levels and impaired iron metabolism due to excessive hepcidin levels are responsible for renal anaemia in patients undergoing haemodialysis. Recently, erythroferrone (ERFE) has been identified as a factor that regulates hepcidin. In addition, fibroblast growth factor 23 (FGF23), which has been recognized as a phosphorus-regulating hormone, appears to be involved in haematopoietic regulation. Clarification of the detailed mechanism of haematopoiesis could lead to the improvement of renal anaemia treatment.

METHODS

Epoetin beta pegol (CERA) was administered to patients undergoing haemodialysis at week 0, and the same amount of CERA with saccharated ferric oxide (SFO) was administered at week 4. The changes in haematopoiesis-related biomarkers, including ERFE, intact FGF23 (iFGF23), C-terminal FGF23 (cFGF23), and inflammatory markers, were examined.

RESULTS

Administration of CERA increased ERFE levels, decreased hepcidin levels, and stimulated iron usage for haematopoiesis, leading to an increase in reticulocytes (Ret) and haemoglobin (Hb). Simultaneous administration of SFO with CERA (CERA + SFO) significantly attenuated the responses of ERFE, Ret, and Hb compared with CERA alone. Although iFGF23 levels were not affected by either CERA or CERA + SFO, cFGF23 was significantly elevated from baseline after CERA. Since cFGF23 levels were not affected by CERA + SFO, cFGF23 levels after CERA + SFO were significantly lower than those after CERA alone. The ratio of iFGF23 to cFGF23 (i/cFGF23 ratio) was significantly higher after CERA + SFO than that after CERA alone. In addition, high-sensitivity C-reactive protein (hsCRP) levels were significantly higher after CERA + SFO than after CERA alone.

CONCLUSION

Administration of SFO suppressed haematopoietic responses induced by CERA. Elevation of i/cFGF23 ratio and hsCRP could account for the inhibitory effects of SFO on haematopoiesis.

TRIAL REGISTRATION

This study was registered with the University Hospital Medical Information Network (ID UMIN000016552 ).

摘要

背景

由于铁调素水平升高导致促红细胞生成素水平降低和铁代谢受损，是接受血液透析的患者发生肾性贫血的原因。最近，红细胞生成素铁蛋白（ERFE）已被确定为调节铁调素的一个因素。此外，成纤维细胞生长因子 23（FGF23）已被认为是一种磷调节激素，似乎参与了造血调节。阐明造血的详细机制可能会改善肾性贫血的治疗效果。

方法

在第 0 周给接受血液透析的患者注射培非格司亭-β（CERA），第 4 周给患者注射等量的 CERA 与蔗糖铁（SFO）。检测 ERFE 等与造血相关的生物标志物、完整成纤维细胞生长因子 23（iFGF23）、C 端成纤维细胞生长因子 23（cFGF23）和炎症标志物的变化。

结果

给予 CERA 可增加 ERFE 水平，降低铁调素水平，并刺激铁用于造血，导致网织红细胞（Ret）和血红蛋白（Hb）增加。与 CERA 单药治疗相比，同时给予 SFO 与 CERA（CERA+SFO）显著减弱了 ERFE、Ret 和 Hb 的反应。虽然 CERA 或 CERA+SFO 对 iFGF23 水平没有影响，但 CERA 后 cFGF23 从基线开始显著升高。由于 CERA+SFO 对 cFGF23 没有影响，因此 CERA+SFO 后的 cFGF23 水平明显低于 CERA 单药治疗后的水平。CERA+SFO 后 iFGF23 与 cFGF23 的比值（i/cFGF23 比值）明显高于 CERA 单药治疗后。此外，CERA+SFO 后高敏 C 反应蛋白（hsCRP）水平明显高于 CERA 单药治疗后。