Optimizing dose and mode of renal replacement therapy in anaemia management

Iron supplementation is probably the most important factor affecting response to treatment with recombinant human erythropoietin (rHuEPO) in patients with renal anaemia. However, the adequacy of dialysis is also significant. Many factors affect the process of dialysis and its effects. The purity of water used to make up the dialysate from concentrate is important. Inhibitors of erythropoiesis including ions and disinfectants may often be present in treated mains water. In addition, microbiological and pyrogenic contamination of the dialysate frequently occurs, sometimes leading to development or aggravation of anaemia in haemodialysis (HD) patients and also causing an immune response via cytokine activation. Inhibitors of erythropoiesis are also present in endogenous blood in patients with impaired renal function. Adequate dialysis is responsible for removing these mainly small, and possibly medium and large inhibitor molecules, thereby improving anaemia and enhancing response to rHuEPO. The biocompatibility and flux of the membrane used in HD may also have an effect. The removal of medium or large inhibitors of erythropoiesis is inefficient with cellulose membranes, but can potentially be achieved by using more permeable, high-flux membranes. However, in patients with adequate dialysis and sufficient iron and vitamin supplementation, the beneficial effects of a switch from standard cellulose to high-flux membranes have yet to be proven conclusively. Another area in which positive results on correction of anaemia have been seen in small studies is in the use of on-line haemodiafiltration, haemofiltration, or sterile dialysate. However, further large, controlled studies are needed to confirm these effects.