Effects of recombinant human erythropoietin on functional and injury endothelial markers in peritoneal dialysis patients

Clinical effects of recombinant human erythropoietin (rHuEPO) such as throm bosis, convulsions, hyperviscosity, hypertension, and angiogenic effect in culture cells have been described. We studied the rHuEPO effect on endothel ial damage markers and endothelial function markers: tissue-type plasminoge n activator (t-PA), nitrate (NO,), thrombomodulin (TM), and von Willebrand factor (vWF). Twenty-six peritoneal dialysis patients treated with rHuEPO a nd 19 controls were included. The study design for rHuEPO patients consisted of four periods: long-term t reatment (rHuEPO-1); 2 months of withdrawal (rHuEPO-2); and 4 months on 500 0 IU/week rHuEPO subcutaneously, with markers being measured after 2 months (rHuEPO-3) and after 4 months (rHuEPO-4). After 2 months of rHuEPO withdrawal, a decrease in hemoglobin level appeare d (11 +/- 1.8 g/dL to 9.2 +/- 1.5 g/dL, p < 0.01). After rHuEPO reintroduct ion, this value reached 10.6 +/- 1.5 g/dL at two months, and 11.1 +/- 1.4 g /dL at four months. A significant increase in t-PA ratio was observed from two months without rHuEPO to two months on rHuEPO, returning to previous va lues after four months. Similarly, TM increased for patients with creatinin e clearances (CrC) < 5 mL/min. No changes in the higher-than-normal plasma vWF levels were found during the various periods. A statistically significa nt lower value was found in controls compared with rHuEPO-4 patients. A sta tistically significant increase in NO, levels was observed in the pre-venou s occlusion (VO) test immediately after the re-introduction of rHuEPO. This increment returned to prior values four months after rHuEPO was reintroduc ed. Our results show that rHuEPO treatment causes an increase in some endotheli al damage markers (TM, t-PA) and modifies endothelial function markers (t-P A ratio, NO,). These changes might favor thrombosis and atherosclerosis.