RHUEPO HYPORESPONSIVENESS - WHO AND WHY

The most common cause of limited response to recombinant human erythro poietin (r-HuEPO) is unrecognized, mild-to-moderate iron deficiency, e ither at the start of treatment or secondary to enhanced iron utilizat ion by newly formed erythrocytes. Iron stores in patients with chronic renal failure (CRF) are often depleted through gastrointestinal bleed ing, blood loss during haemodialysis, and blood sampling. Mobilization of iron stores may be inadequate, especially during rapid haemoglobin regeneration. Aluminium overload may also interfere with gastrointest inal and cellular iron uptake. Overt or unrecognized infection or infl ammation is another common cause of hyporesponsiveness, and is a conse quence of increased blood concentrations of cytokines such as tumour n ecrosis factor (TNF), interleukin-l (IL-1), and interferon-gamma (IFN- gamma), which suppress erythrocyte stem-cell proliferation. Less commo n causes include severe secondary hyperparathyroidism and myeloma (dur ing chemotherapy). Response to r-HuEPO can be best predicted by baseli ne fibrinogen (a marker of subclinical inflammation); baseline transfe rrin receptor (sTfR) concentrations (a marker of functional iron defic iency); and sTfR increment after 2 weeks (a marker of early change in erythropoietic activity).