Dialysis adequacy and response to erythropoietic agents: what is the evidence base?

Anaemia secondary to chronic kidney disease is a complex syndrome. Adequate dialysis can contribute to its correction by removing small, and possibly middle/large molecules, that may inhibit erythropoiesis. A clear relationship between higher haemoglobin or haematocrit levels, lower recombinant human erythropoietin (epoetin) dose and increase in dialysis dose has been reported in a number of prospective and retrospective studies. This is particularly true in patients receiving inadequate dialysis. Increased attention has also been paid to the relationship between dialysis, increased inflammatory stimulus and response to erythropoietic therapy, as dialysate contamination and low-compatible treatments may increase the production of cytokines and consequently inhibit erythropoiesis. As middle-/large-molecular-weight inhibitors can only be adsorbed or removed by more permeable membranes, the biocompatibility of dialysis membranes and flux are also important factors. In highly selected, adequately dialysed patients without iron or vitamin depletion, however, the effect of these treatment modalities on anaemia appears to be smaller than expected. The role of on-line treatments is still controversial; moreover, it is still difficult to discriminate between the effects of on-line haemodiafiltration per se (use of high-flux biocompatible membranes and pyrogen-free dialysate) from that of an increased dialysis dose. Prospective, randomized, adequately sized studies on this topic are still needed. Results, albeit very preliminary, obtained with short or long nocturnal daily haemodialysis on anaemia correction are encouraging. Adequate dialysis is not only a tool for reducing morbidity and mortality of haemodialysis patients, but is also a way of optimizing responsiveness to erythropoietic therapy, allowing easier achievement of anaemia correction in a higher percentage of patients.