Nowadays, it is widely recognized that anaemia bears a great responsibility for the increased morbidity and mortality of patients with end-stage renal disease (ESRD). The advent of recombinant human erythropoietin (rHu EPO) represented a revolution in the field of nephrology allowing avoidance of blood transfusions, reduction in the risk of sensitization, prevention of iron overload and improved exercise tolerance cognitive capacity, sexual function and quality of life. Thus the treatment of anaemia was deeply transformed.

Since recombinant human EPO became available in 1986, millions of patients have received the hormone for correction of renal and non renal anaemia.

Recombinant human erythropoietin (rHu-EPO) is a sialoglycoprotein hormone that appears to be immunologically and biologically equivalent to the endogenous compound enhancing erythropoiesis dose proportionally. The recombinant product is structurally very similar to native human erythropoietin being a 193 - amino acid peptide from which a 27 - amino acid leader sequence is cleaved.

Still several questions and problems remain concurring the use of rhu EPO. In all, there are three main problems associated with the use of rhu EPO : cost, pure red cell aplasia (PRCA) and side effects such as hypertension.

With respect to side effects some new concerns are emerging. Patients on treatment with rhu EPO have shown sudden resistance to rhu EPO with development of anti-erythropoietin antibodies (anti-EPO) which are able to neutralize erythropoietin molecules produced by the patients. Until 1998 only 3 patients were fully documented as having anti-EPO antibodies. But a recent report suggests that upto 67% of patients treated with rHu EPO develop anti-EPO antibodies.

Detecting these antibodies remained a challenge till about a decade back. But with the advent of radioisotopically labeled Erythropoietin, it has become possible to measure these circulating antibodies. We have developed and standardized a very sensitive and specific procedure in our hospital to monitor circulating anti-EPO antibodies. This procedure has gone a long way in helping the physicians to decide the course of alternative treatment for such patients.

It has been recommended that if anti-EPO antibodies are found in a patient, rHu EPO should be discontinued immediately and challenging these patients with another erythropoietin protein is not recommended for the antibodies have been shown to cross-react with all available recombinant erythropoietin products. It has been observed that a decrease or withdrawal of rhu-EPO results in decrease in antibody titre concomitant with an increase in reticulocyte count. Most patients with PRCA associated with rHu EPO have received different immuno suppressive treatments, including mmunoglobulin, steroids, cyclophosphamide, cyclosporin and plasmapheresis. In most cases antibodies were not detectable after these therapies and erythropoiesis recovered with the patients transfusion requirements becoming similar to these prior to rhu EPO treatment.

Many questions concerning PRCA in patients treated with rHu EPO remain unsolved, it is therefore important to study further the aetiopathogenesis of this complication and possibly adjust preventive and therapeutic measures. Thus measurement of antibodies to EPO using a sensitive radioassay method may serve as a guideline for the management of anaemia, since EPO resistance seems relative rather than absolute in many patients.