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促红细胞生成素刺激剂对透析患者循环内皮祖细胞的多效作用。

Pleiotropic effect of erythropoiesis-stimulating agents on circulating endothelial progenitor cells in dialysis patients.

机构信息

Department of Medicine, Tokyo Rosai Hospital, Tokyo, Japan.

Department of Medicine, Medical Center East, Tokyo Women's Medical University, Tokyo, Japan.

出版信息

Clin Exp Nephrol. 2021 Oct;25(10):1111-1120. doi: 10.1007/s10157-021-02071-2. Epub 2021 Jun 9.


DOI:10.1007/s10157-021-02071-2
PMID:34106373
Abstract

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.

摘要

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。

相似文献

[1]
Pleiotropic effect of erythropoiesis-stimulating agents on circulating endothelial progenitor cells in dialysis patients.

Clin Exp Nephrol. 2021-10

[2]
Modulation of circulating endothelial progenitor cells by erythropoiesis-stimulating agents in patients with chronic kidney disease stage G5 and 5D
.

Clin Nephrol. 2016-11

[3]
Associations among Erythroferrone and Biomarkers of Erythropoiesis and Iron Metabolism, and Treatment with Long-Term Erythropoiesis-Stimulating Agents in Patients on Hemodialysis.

PLoS One. 2016-3-15

[4]
Impact of Switching From Darbepoetin Alfa to Epoetin Beta Pegol on Iron Utilization and Blood Pressure in Peritoneal Dialysis Patients.

Ther Apher Dial. 2015-10

[5]
Long-term maintenance of hemoglobin levels in hemodialysis patients treated with bi-weekly epoetin beta pegol switched from darbepoetin alfa: a single-center, 12-month observational study in Japan.

J Artif Organs. 2019-6

[6]
Comparison of pain and efficacy of darbepoetin alfa and epoetin Beta pegol treatment in patients receiving peritoneal dialysis.

J Nippon Med Sch. 2015

[7]
A randomized control study on the procedure for switching epoetin beta (EPO) to epoetin beta pegol (CERA) in the treatment of renal anemia in maintenance hemodialysis patients.

Blood Purif. 2014

[8]
Anemia Treatment by Erythropoiesis-stimulating Agents during the 6 Months before the Initiation of Hemodialysis: Comparison of Darbepoetin Alfa and Continuous Erythropoietin Receptor Activator.

Keio J Med. 2017-9-26

[9]
Changes in hepcidin and reticulocyte hemoglobin equivalent levels in response to continuous erythropoietin receptor activator administration in hemodialysis patients: a randomized study.

Ther Apher Dial. 2014-10

[10]
Effects of three kinds of erythropoiesis-stimulating agents on renal anemia in Japanese non-dialysis chronic kidney disease patients.

Clin Exp Nephrol. 2014-10

引用本文的文献

[1]
A Promising Candidate in Tendon Healing Events-PDGF-BB.

Biomolecules. 2022-10-20

[2]
The Role of Endothelial Progenitor Cells in Atherosclerosis and Impact of Anti-Lipemic Treatments on Endothelial Repair.

Int J Mol Sci. 2022-2-28

本文引用的文献

[1]
Types of Erythropoietin-Stimulating Agents and Mortality among Patients Undergoing Hemodialysis.

J Am Soc Nephrol. 2019-4-23

[2]
Long-term maintenance of hemoglobin levels in hemodialysis patients treated with bi-weekly epoetin beta pegol switched from darbepoetin alfa: a single-center, 12-month observational study in Japan.

J Artif Organs. 2019-6

[3]
PI3K/Akt and HIF‑1 signaling pathway in hypoxia‑ischemia (Review).

Mol Med Rep. 2018-8-9

[4]
Modulation of circulating endothelial progenitor cells by erythropoiesis-stimulating agents in patients with chronic kidney disease stage G5 and 5D
.

Clin Nephrol. 2016-11

[5]
Circulating Endothelial Progenitor Cells and Clinical Outcome in Patients with Aortic Stenosis.

PLoS One. 2016-2-25

[6]
The Different Association between Serum Ferritin and Mortality in Hemodialysis and Peritoneal Dialysis Patients Using Japanese Nationwide Dialysis Registry.

PLoS One. 2015-11-23

[7]
Effects of Long-Term Erythropoiesis-Stimulating Agents on Iron Metabolism in Patients on Hemodialysis.

Ther Apher Dial. 2015-12

[8]
Matrix metalloproteinases in atherosclerosis: role of nitric oxide, hydrogen sulfide, homocysteine, and polymorphisms.

Vasc Health Risk Manag. 2015-2-27

[9]
Hepcidin-25, mean corpuscular volume, and ferritin as predictors of response to oral iron supplementation in hemodialysis patients.

Nutrients. 2014-12-29

[10]
Twice-monthly administration of a lower dose of epoetin beta pegol can maintain adequate hemoglobin levels in hemodialysis patients.

Ther Apher Dial. 2015-4

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