Division of Nephrology, Department of Medicine, Showa University School of Medicine, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo, 142-8666, Japan.
Shibagaki Clinic Jiyugaoka, Tokyo, Japan.
Sci Rep. 2023 Feb 23;13(1):3181. doi: 10.1038/s41598-023-30331-6.
This study aimed to confirm changes in biomarkers of erythropoiesis and iron metabolism and serum fibroblast growth factor 23 (FGF-23) during darbepoetin-α treatment and then switching to the hypoxia-inducible factor prolyl hydroxylase inhibitor roxadustat. A total of 28 patients on hemodialysis who received weekly doses of darbepoetin-α were switched to roxadustat. Biomarkers for erythropoiesis and iron metabolism and intact and C-terminal FGF-23 were measured in blood samples collected before the HD session on days - 7 (darbepoetin-α injection), - 4, and - 2, and days 0 (switch to roxadustat treatment, three times weekly), 3, 5, 7, 14, 21, and 28. Erythropoietin and erythroferrone levels were elevated on day - 4 by darbepoetin-α injection and decreased to baseline levels at day 0. Levels of erythropoietin were not significantly increased by roxadustat supplementation, but erythroferrone levels were continuously elevated, similar to darbepoetin-α treatment. Hepcidin-25 and total iron binding capacity were significantly decreased or increased in patients treated with roxadustat compared with darbepoetin-α. Changes of intact and C-terminal FGF-23 levels were parallel to changes of phosphate levels during roxadustat treatment. However, the actual and percentage changes of intact FGF-23 and C-terminal FGF-23 in patients with low ferritin levels were greater than those in patients with high ferritin levels. Roxadustat might stimulate erythropoiesis by increasing iron usage through hepcidin-25, which was suppressed by erythroferrone in the physiological erythropoietin condition. Changes of intact FGF-23 and C-terminal FGF-23 levels might be affected by roxadustat in patients on hemodialysis, especially those with a low-iron condition.
这项研究旨在确认在接受达贝泊汀-α治疗后转换为缺氧诱导因子脯氨酰羟化酶抑制剂罗沙司他时，红细胞生成和铁代谢以及血清成纤维细胞生长因子 23（FGF-23）的生物标志物的变化。共 28 名接受每周达贝泊汀-α剂量的血液透析患者转换为罗沙司他。在血液透析前一天（达贝泊汀-α注射日）、-4 天和-2 天以及 0 天（转换为罗沙司他治疗，每周三次）、3 天、5 天、7 天、14 天、21 天和 28 天采集血样，测量红细胞生成和铁代谢以及完整和 C 端 FGF-23 的生物标志物。达贝泊汀-α注射后第-4 天，促红细胞生成素和红细胞生成素铁蛋白水平升高，并在第 0 天降至基线水平。罗沙司他补充并未显著增加促红细胞生成素水平，但红细胞生成素铁蛋白水平持续升高，与达贝泊汀-α治疗相似。与达贝泊汀-α相比，用罗沙司他治疗的患者的转铁蛋白 25 和总铁结合能力显著降低或升高。在罗沙司他治疗期间，完整和 C 端 FGF-23 水平的变化与磷酸盐水平的变化平行。然而，低铁蛋白水平患者的完整 FGF-23 和 C 端 FGF-23 的实际和百分比变化大于高铁蛋白水平患者。罗沙司他可能通过增加铁的使用来刺激红细胞生成，这在生理促红细胞生成素条件下被红细胞生成素铁蛋白抑制。在血液透析患者中，完整 FGF-23 和 C 端 FGF-23 水平的变化可能受罗沙司他的影响，尤其是在铁缺乏的情况下。
