Department of Medicine, Tokyo Rosai Hospital, Tokyo, Japan.
Department of Medicine, Medical Center East, Tokyo Women's Medical University, Tokyo, Japan.
Clin Exp Nephrol. 2021 Oct;25(10):1111-1120. doi: 10.1007/s10157-021-02071-2. Epub 2021 Jun 9.
BACKGROUND: Recent studies have suggested that erythropoiesis-stimulating agents (ESAs) may accelerate not only angiogenesis but also vasculogenesis, beyond erythropoiesis. METHODS: We conducted a 12-week prospective study in 51 dialysis patients; 13 were treated with recombinant human erythropoietin (EPO, 5290.4 ± 586.9 IU/week), 16 with darbepoetin (DA, 42.9 ± 4.3 µg/week), 12 with epoetin β pegol (CERA, 40.5 ± 4.1 µg/week) and 10 with no ESAs. Vascular mediators comprising endothelial progenitor cells (EPCs), vascular endothelial growth factor (VEGF), matrix metalloproteinase-2 (MMP-2), and high-sensitivity C-reactive protein (hs-CRP) were measured at 0 and 12 weeks. EPCs were measured by flow cytometry as CD45CD34CD133 cells. RESULTS: The EPC count increased significantly to a greater extent in the EPO group than in the other three group, and increased significantly from 0 to 12 weeks in a EPO dose-dependent manner. In both the DA and CERA groups, the EPC count did not change at 12 weeks. Serum levels of VEGF, MMP-2 and hs-CRP were not affected by ESA treatment in all groups. In the CERA group, serum ferritin decreased significantly compared to the no-ESA group and correlated with CERA dose, although use of iron was permitted if required during the prospective study period of 12 weeks. CONCLUSIONS: When patients on dialysis were treated with clinical doses of various ESAs, only EPO induced a significant increase of circulating EPCs from bone marrow, whereas, DA and CERA had no effect.
背景:最近的研究表明,促红细胞生成素刺激剂(ESAs)不仅可以加速红细胞生成,还可以加速血管生成和血管发生。
方法:我们对 51 名透析患者进行了为期 12 周的前瞻性研究;其中 13 例接受重组人促红细胞生成素(EPO,5290.4±586.9 IU/周)治疗,16 例接受达贝泊汀(DA,42.9±4.3 µg/周)治疗,12 例接受聚乙二醇化重组人促红细胞生成素(CERA,40.5±4.1 µg/周)治疗,10 例未接受 ESA 治疗。分别于 0 周和 12 周时检测血管生成介质,包括内皮祖细胞(EPC)、血管内皮生长因子(VEGF)、基质金属蛋白酶-2(MMP-2)和高敏 C 反应蛋白(hs-CRP)。通过流式细胞术检测 EPC,采用 CD45CD34CD133 细胞进行测定。
结果:EPO 组的 EPC 计数显著增加,且增加程度大于其他三组,且 EPO 剂量依赖性地从 0 周增加至 12 周。在 DA 和 CERA 两组中,EPC 计数在 12 周时均无变化。各组 ESA 治疗均未影响 VEGF、MMP-2 和 hs-CRP 的血清水平。在 CERA 组,与无 ESA 组相比,血清铁蛋白显著下降,且与 CERA 剂量相关,尽管在 12 周的前瞻性研究期间允许根据需要使用铁剂。
结论:当透析患者接受各种临床剂量的 ESA 治疗时,只有 EPO 能从骨髓中显著增加循环 EPC,而 DA 和 CERA 则没有这种作用。
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