Effects of Recombinant Erythropoietin Therapy on Circulating Endothelial Markers in Hemodialysis Patients

Effects of a 4-week course of recombinant human erythropoietin (rHuEpo) therapy on four circulating endothelium-derived cardiovascular risk markers were studied in 20 patients receiving maintenance hemodialysis in relation to surrogates of chronic inflammation, liver function, and arterial blood pressure. Soluble intercellular adhesion molecule-1 (sICAM-1), antigens of plasminogen activator inhibitor-1 (PAI-1:Ag) and von Willebrand factor (vWF:Ag), and soluble thrombomodulin (sTM) were determined by immunoenzymatic assays. C-reactive protein; alpha1 acid-glycoprotein; alpha1-antitrypsin; immunoglobulin M, A, and G; interleukin-6; lipoprotein(a); fibrinogen; total protein; albumin; total cholesterol; hepatitis B and C markers; liver enzymes; prothrombin time; and phosphorus were measured by routine methods. The rHuEpo treatment resulted in a 25% increase in sICAM-1 (Wilcoxon's p = 0.001), a 50% increase in PAI-1:Ag (p = 0.004), a 15% increase in sTM (p = 0.002), and did not change vWF:Ag levels. The increase in sICAM-1 concentration directly correlated with that of PAI-1:Ag (Spearman's rho = 0.483, p = 0.031). The rHuEpo-induced increases in hemoglobin, platelets, and pre-dialysis diastolic blood pressure levels did not correlate with the increments in the endothelial markers studied. In conclusion, short-term rHuEpo therapy activates vascular endothelium in patients receiving maintenance hemodialysis. This specific effect may influence cardiovascular risk.