title: 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.
authors.affiliation: Department of Medicine, Cardiovascular Division, Vascular Medicine Section, University of Pennsylvania School of Medicine, PA, USA. mohlere@uphs.upenn.edu
authors.forename: Emile R
authors.initials: ER
authors.lastname: Mohler
authors.lastname: Lifeng Zhang
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Medenilla
authors.forename: Wade
authors.initials: W
authors.lastname: Rogers
authors.forename: Benjamin
authors.initials: B
authors.lastname: French
authors.forename: Andrew
authors.initials: A
authors.lastname: Bantly
authors.forename: Jonni S
authors.initials: JS
authors.lastname: Moore
authors.lastname: Yonghong Huan
authors.forename: Miho
authors.initials: M
authors.lastname: Murashima
authors.forename: Jeffrey S
authors.initials: JS
authors.lastname: Berns
mesh_terms: D000071916:AC133 Antigen; D000368:Aged; D015703:Antigens, CD / Q000097:blood; D018952:Antigens, CD34 / Q000097:blood; D015415:Biomarkers / Q000097:blood; D049109:Cell Proliferation / Q000187:drug effects; D002908:Chronic Disease; D000068256:Darbepoetin alfa; D003924:Diabetes Mellitus, Type 2 / Q000150:complications*; D003928:Diabetic Nephropathies / Q000097:blood / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology / Q000503:physiopathology; D042783:Endothelial Cells / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D004921:Erythropoietin / Q000031:analogs & derivatives* / Q000627:therapeutic use; D005260:Female; D006023:Glycoproteins / Q000097:blood; D006397:Hematinics / Q000627:therapeutic use*; D006801:Humans; D007674:Kidney Diseases / Q000097:blood / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology / Q000503:physiopathology; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D010455:Peptides / Q000097:blood; D015143:Philadelphia; D011446:Prospective Studies; D013234:Stem Cells / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D013997:Time Factors; D016896:Treatment Outcome; D014664:Vasodilation / Q000187:drug effects
chemical_list: D000071916:AC133 Antigen; D015703:Antigens, CD; D018952:Antigens, CD34; D015415:Biomarkers; D006023:Glycoproteins; D006397:Hematinics; C000606023:PROM1 protein, human; D010455:Peptides; D004921:Erythropoietin; D000068256:Darbepoetin alfa