Novel aspects of erythropoietin response in renal failure patients.

The invention of recombinant human erythropoietin (rHuEpo) for the treatment of renal anaemia was a hallmark in the care of patients with renal insufficiency. Recently published guidelines (European Best Practice Guidelines, NKF-DOQI) have set the target haemoglobin to be reached by treatment with rHuEpo to >11 g/dl. Normalizing haemoglobin levels may reduce morbidity and mortality and improve quality of life in haemodialysis patients. During long-term treatment, most patients will not respond adequately to therapy with rHuEpo alone. The most important confounding factor, limiting the effectiveness of rHuEpo, is absolute or functional iron deficiency, which is now recognized and treated in many dialysis units. However, there are several other adjuvant treatment options which may help to optimize the response to treatment with rHuEpo. A weekly dose of 2-3 mg of folic acid and 100-150 mg of vitamin B6 is recommended for haemodialysis patients on rHuEpo therapy. The addition of 0.25 mg/month of vitamin B12 may be necessary in selected patients. Vitamin C (1-1.5 g/week) was shown to overcome functional iron deficiency in patients with high ferritin levels. The potential increase of oxidative stress induced by intravenous iron therapy may be blunted by concomitant administration of vitamin E (1200 IU). There is clear evidence from the literature that treatment of secondary hyperparathyroidism by vitamin D improves erythropoiesis. The most recently discovered biological effects of rHuEpo include the induction of several genes in endothelial cells as well as a role for erythropoietin in the outcome of plasmodium infection. A new erythropoietin-like molecule is novel erythropoiesis stimulating protein (NESP), which is as effective and safe as rHuEpo, with the potential advantage of less frequent dosing.