Optimal use of epoetin-alpha in the anaemia of chronic renal failure

Anaemia, a major feature of chronic renal failure, is responsible for a significant proportion of the multisystemic disabling symptoms in patients with chronic renal failure (CRF). Anaemia correction with recombinant human erythropoietin (epoetin-alpha) often leads to significant amelioration of these symptoms. Starting dose should be 50 U/kg of bodyweight given subcutaneously or intravenously 1, 2 or 3 times a week. The subcutaneous route is more effective, resulting in use of less epoetin-alpha and subsequent cost-saving. Adverse effects of epoetin-alpha tend to be more severe and more likely following intravenous administration. Once the target haematocrit is achieved, the epoetin-alpha dose should be reduced by 50 to 80%, but should not be stopped, since an abrupt fall in haematocrit may ensue if epoetin-alpha is completely discontinued. There is an emerging consensus that it is deleterious, and not necessary, to allow patients to become severely anaemic before starting epoetin-alpha. Thus, the current trend is to start epoetin-alpha once the haematocrit is 30 to 35%. On the other hand, what the target haematocrit should be is controversial. The threshold haematocrit beyond which the risks of anaemia correction outweigh the benefits in patients with CRF is not established. Studies that assessed quality of life outcomes as well as clinical experience in Europe clearly demonstrate better outcomes without adverse effects in patients with a haematocrit between 36 to 40%, compared to those with haematocrit of 30%. Prior to starting epoetin-alpha in any patient with CRF, a methodological evalution should be performed to exclude other major causes of anaemia and to identify any comorbid conditions that may impair response to epoetin-alpha. Response to epoetin-alpha may be impaired by loss of residual renal function in patients with progressive CRF or kidney transplant recipients. Other major factors that impair response to epoetin-alpha include impaired utilisation of iron, absolute iron deficiency, inadequate dialysis, infection and bone marrow fibrosis.