Erythropoietin is a glycoprotein hormone with a long and controversial history. Thousands of patients worldwide rely on synthetic erythropoietins such as epoetin alfa to alleviate the anaemia that accompanies chronic renal disease and chemotherapy for cancer. But despite decades of use, experts can't seem to agree on one fundamental aspect of treatment: how aggressively should doctors use these agents to drive patients' concentrations of haemoglobin back towards normal?

Getting the answer should be a relatively simple matter—a few decent trials comparing the various options, usually full or partial correction of anaemia. But in the case of epoetin the truth has been lost in a blizzard of professional polemic complicated by the vested interests of big business. Balance is critical. Too little treatment and patients with chronic kidney disease are condemned to a lifetime of exhaustion, misery, and blood transfusions. Too much and they could be threatened with an increased risk of death.1 Add to this the fact that synthetic erythropoietin is a lucrative best seller for a company with a virtual monopoly in the US, and a fairly straightforward clinical issue becomes a whole lot more complicated. Overtreatment is emerging as a real problem, particularly for US patients on haemodialysis. Over half have haemoglobin concentrations above those recommended by the Food and Drugs Administration, according to one leading commentator.2

The simmering controversy about the best haemoglobin concentration for patients with chronic kidney disease eventually boiled over in November last year when the New England Journal of Medicine published two trials showing that aiming too high was at best an expensive waste of time and, at worst, dangerous.3 4 Both trials enrolled patients …