Dialysate related cytokine induction and response to recombinant human erythropoietin in haemodialysis patients

Background. Chronic inflammatory disorders or infections represent a major cause of hyporesponsiveness to recombinant human erythropoietin (rHuEpo). T o test the hypothesis that dialysate-related cytokine induction alters the response to rHuEpo, we conducted a prospective study with matched pairs of chronic haemodialysis patients. We compared the effect of two dialysis flui ds, differing in their microbiological quality, on the rHuEpo therapy. Methods. Thirty male patients with end-stage renal disease maintained on re gular haemodialysis were assigned either to a group treated with convention al (potentially microbiologically contaminated) dialysate (group I) or to a group treated with online-produced ultrapure dialysate (group II). Randomi zation was stratified according to the maintenance dose of rHuEpo necessary to maintain a target haemoglobin level of 10-10.5 g/dl. Patients were foll owed for 12 months. Kt/V was calculated by the formula of Daugirdas. Haemog lobin levels were measured weekly and serum ferritin concentrations were de termined at 6-week intervals. C-reactive protein (CRP) and interleukin-6 (I L-6) was measured by an ELISA at the start of the study and after 3, 6 and 12 months. Results. In group I, continuous use of bicarbonate dialysate did not change the rHuEpo dosage given to achieve the target haemoglobin level and was as sociated with elevated surrogate markers (CRP, IL-6) of cytokine-induced in flammation. The switch from conventional to online-produced ultrapure dialy sate in group II resulted in a lower bacterial contamination with a signifi cant decrease of CRP and IL-6 blood levels. It was accompanied by a signifi cant and sustained reduction of the rHuEpo dosage, which was required to co rrect the anaemia. Using multiple regression analysis, IL-6 levels are show n to have a strong predictive value for rHuEpo dosage in both groups. Conclusion. Our data demonstrate that dialysate-related factors such as low bacterial contamination can induce the activation of monocytes, resulting in elevated serum levels of IL-6. Dialysate-related cytokine induction migh t diminish erythropoiesis. The use of pyrogen free ultrapure dialysate resu lted in a better response to rHuEpo. Not only would it save money, but it w ould also help to maintain an optimal haemoglobin level without further inc rease in rHuEpo dosage.