Should be fully investigated and treated

Recombinant human erythropoietin was licensed for the treatment of renal anaemia five years ago, and over 90% of patients respond to it.1 But the few who do not are important both in clinical and financial terms: a 70 kg man failing to respond to a dose of 200 U/kg/week currently costs the NHS pounds sterling6500 a year.

The definition of a poor response to erythropoietin is arbitrary. As most patients with renal anaemia respond to 75-150 U/kg/week any such patient showing a rise in haemoglobin concentration of less than 10 g/l/month despite a dose of greater than 200 U/kg/week may be classed as a “poor responder.” Several factors may be responsible: important causes include iron deficiency,2 3 blood loss,4 infection, and inflammatory conditions, including malignancy.5 6 Other causes include hyperparathyroidism with marrow fibrosis,7 aluminium toxicity,8 vitamin B-12 or folate deficiency,9 haemolysis,10 marrow dysfunction,11 red cell enzyme defects, and haemoglobinopathies.12 13

How do these conditions impair the response to erythropoietin? In some the pathogenesis is obvious—for example, absolute iron deficiency results in resistance to erythropoietin because iron is essential for synthesis of haem. But normal or even increased iron stores (as judged by the serum ferritin concentration) do not exclude the development of functional iron deficiency, in which iron stores are ample but there is a failure of supply of iron to the marrow or its use in erythropoiesis.3 Functional iron deficiency is the commonest cause of resistance to erythropoietin and is probably underdiagnosed, mainly because reliable markers for its detection are …