Effect of darbepoetin alfa on endothelial progenitor cells and vascular reactivity in chronic kidney disease

Abstract

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.

Erythropoietin attenuates cardiac dysfunction by increasing myocardial angiogenesis and inhibiting interstitial fibrosis in diabetic rats

“…It is now becoming increasingly clear that EPO plays a protective role in the body outside of its erythropoietic effects. Previous studies identified the protective effects of EPO on different molecular pathways in ischemic tissues in the heart, kidney, and brain [5,14,15]. There are very few studies describing an effect of EPO treatment on diabetic cardiac tissue [16].…”

Sodium nitrite in patients with peripheral artery disease and diabetes mellitus: Safety, walking distance and endothelial function

“…There are several drugs that demonstrated improvement in endothelial function including HMG-CoA reductase inhibitors, [24][25][26] erythropoietin (and analogues), 27 and modulators of the renin-angiotensin system. [28][29][30] The data derived from this study indicate that oral administration of sodium nitrite in the doses administered is safe and the 80 mg BID dose may afford protection against worsening endothelial function among patients with PAD and diabetes.…”

Epoetin beta pegol prevents endothelial dysfunction as evaluated by flow-mediated dilation in chronic kidney disease rats

“…Erythropoietin (EPO) receptors are widely distributed in both hematopoietic cells and non-hematopoietic cells, including neurons, cardiomyocytes, peritubular and mesangial cells, and vascular cells such as endothelial and smooth muscle cells (Khoshdel et al, 2008). Although several reports have demonstrated that ESAs have potential benefits against endothelial dysfunction (Bahlmann et al, 2004;Mohler et al, 2011;Toba et al, 2011), these endothelial protective effects of ESAs have been observed under doses that had no influence on hemoglobin, and it is unclear whether appropriate treatment of ESA exerts endothelial protective effects under amelioration of anemia.…”