DMT1 (NRAMP2/DCT1) Genetic Variability and Resistance to Recombinant Human Erythropoietin Therapy in Chronic Kidney Disease Patients under Haemodialysis

摘要

The management of anaemia in chronic kidney disease (CKD) was changed by the introduction of recombinant human erythropoietin (rhEPO) therapy, allowing a significant correction of anaemia; however, around 5-10% of the patients show a marked resistance to rhEPO therapy. Several conditions were reported as being associated with rhEPO resistance, but changes in iron ho-meostasis is one of the most studied causes.CKD patients who do not respond to rhEPO therapy seem to present a 'functional' iron deficiency, characterized by the presence of adequate iron stores as defined by conventional criteria, but apparently with an inability to sufficiently mobilize this iron to adequately support erythropoiesis. We recently found that compared with responder patients, non-responders presented no statistical differences for iron, transferrin saturation and ferri-tin values, but had a significantly lower haemoglobin concentration and mean cell haemoglobin, as well as significantly higher plasma levels of the soluble transferrin receptor (s-TfR).