Effect of darbepoetin alfa on endothelial progenitor cells and vascular reactivity in chronic kidney disease
Effect of darbepoetin alfa on endothelial progenitor cells and vascular reactivity in chronic kidney disease
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DOI：
10.1177/1358863x11408639
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发表时间：
2011-06-01
影响因子：
3.5
通讯作者：
Berns, Jeffrey S.
中科院分区：
文献类型：
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作者：
Mohler, Emile R., III;Zhang, Lifeng;Berns, Jeffrey S.
内皮祖细胞被认为是维持正常血管功能的重要细胞。我们进行了一项前瞻性研究，评估红细胞生成刺激剂Darbepoetin alfa对伴有或不伴有糖尿病的慢性肾脏疾病(CKD)患者的EPC和血管功能的影响。30例慢性肾脏病患者(其中20例为II型糖尿病患者，10例为非糖尿病患者)每周皮下注射达贝泊丁，疗程为4周。分别于用药前、用药后2周和4周测定内皮祖细胞。用臂部超声检测血管功能，用细胞增殖法测定细胞活性。达贝泊丁治疗4周后，CD133、CD34、CD146和CD146/31表达细胞显著增加(均P<0.05)，血流介导的血管扩张增加2.1%，95%可信区间：(0.4%，3.8%)，集落形成单位增加2倍，95%可信区间：(1.7，2.3)。糖尿病患者内皮祖细胞亚群(CD133(+)和34(+)，p<；0.01和p=0.06)增加，血管扩张和增殖。总而言之，服用达贝泊丁4周后，内皮祖细胞亚群增加，内皮功能改善，细胞增殖增加，包括糖尿病患者，这与血管健康的有利改善是一致的。
Endothelial progenitor cells (EPCs) are thought to be important for maintaining normal vascular function. We conducted a prospective study evaluating the effect of the erythropoiesis-stimulating agent darbepoetin alfa on EPCs and vascular function in patients with chronic kidney disease (CKD), with or without diabetes. Thirty subjects with CKD (20 subjects with type II diabetes mellitus and 10 without diabetes mellitus) received weekly subcutaneous administration of darbepoetin alfa for 4 weeks. EPCs were measured at baseline and 2 and 4 weeks after drug administration. Vascular function was measured with brachial ultrasound and cell activity was measured with a cell proliferation assay. Cells expressing CD133, CD34, CD146 and CD146/31 were significantly elevated (all p < 0.05), flow-mediated vasodilatation increased 2.1%, 95% CI: (0.4%, 3.8%) and colony-forming units increased twofold, 95% CI: (1.7, 2.3) after 4 weeks of treatment with darbepoetin alfa. Subjects with diabetes exhibited an increase in a subset of EPCs (CD133(+) and 34(+), p < 0.01 and p = 0.06, respectively), vasodilatation and proliferation. In conclusion, the administration of darbepoetin alfa for 4 weeks increased a subset of EPCs, improved endothelial function and increased cell proliferation, including those with diabetes, which is consistent with a favorable improvement in vascular health.