Haemoglobin targets: we were wrong, time to move on

Anaemia occurs in nearly all patients with moderate-to-severe chronic kidney disease. The most widely used treatment options are erythropoiesis-stimulating agents (eg, Epogen, Procrit, and Aranesp), with an economic burden of US$10 billion in sales worldwide in 2006, and $2 billion Medicare expenditure for dialysis patients in 2006 in the USA alone.1
Administration of erythropoietin rapidly increases haemoglobin concentrations in most patients with chronic kidney disease. Observational studies have shown that increased concentrations of haemoglobin are associated with improved quality of life and survival in chronic kidney disease.2
Notwithstanding the widely accepted benefits of proper management of anaemia in chronic kidney disease, debate has raged about the optimum haemoglobin target concentrations. This uncertainty has been a dominant theme in nephrology research and practice since the US Food and Drug Administration licensed synthetic erythropoietin in 1989, on the basis of little controlled data and with almost exclusive emphasis on quality of life, a surrogate endpoint.3
For almost 20 years, there have been debates on anaemia in general, and haemoglobin targets in particular, which have been a major topic in nephrology journals and meetings worldwide, seemingly disproportionate to the clinical importance of the topic and the quantity of valid data from controlled trials in the context of other major themes in nephrology research. These debates, based mainly on observational data, have supported the coincidence of normalisation or optimisation of haemoglobin with the concept of increasing concentrations to a maximum, and suggested survival advantages, even though trials and meta-analyses clearly pointed in the opposite direction.4