LONG-TERM EFFECTS OF ERYTHROPOIETIN THERAPY ON FISTULA STENOSIS AND PLASMA-CONCENTRATIONS OF PDGF AND MCP-1 IN HEMODIALYSIS-PATIENTS

Among the adverse effects possibly associated with the use of erythrop oietin (EPO) in hemodialysis patients is an increased incidence of thr ombosis of the vascular access. However, little is known about the eff ect of EPO on the stenotic lesion in the venous outflow system, which is the leading cause of fistula thrombosis. This study was designed to explore the long-term effects of EPO treatment on progressive fistula stenosis and the plasma concentrations of some potential mediators of neointimal hyperplasia. A cross-sectional and 3-yr prospective, place bo-controlled, pilot study was performed in 30 hemodialysis patients w ith native arteriovenous fistula. Sixteen patients received EPO and 14 received a placebo. Venous dialysis pressure, urea recirculation, col or Doppler sonography, and angiography were used to monitor vascular a ccess patency. Compared with 60 healthy subjects, the hemodialysis pat ients had elevated plasma levels of platelet-derived growth factor, mo nocyte chemoattractant protein-1, and interleukin 6, three proteins th at might be involved in the neointima formation regulating the prolife ration of vascular smooth muscle cells. In addition, these patients ha d numerous endothelial and hemostatic abnormalities that indicated a t hrombophilic state. Eleven patients, six (37.5%) receiving EPO and fiv e (35.7%) taking placebo, developed a progressive stenosis in the veno us circuit of the fistula. There was no significant difference in the vascular access, event-free survival over 36 mo between patients recei ving EPO therapy and placebo. EPO induced a significant decrease in th e plasma values of platelet-derived growth factor and vascular cell ad hesion molecule-1 and an increase of monocyte chemoattractant protein- 1 concentration. After EPO withdrawal, these parameters returned to pr etreatment levels. In conclusion, long-term EPO therapy does not incre ase the risk of progressive stenosis of native arteriovenous fistula. The use of erythropoietin does not induce any prothrombotic change in hemostatic parameters, and further studies are required to elucidate t he theoretically beneficial effects on the plasma concentration of som e potential mediators of neointimal formation.