Anaemia, rHuEPO resistance, and cardiovascular disease in end-stage renal failure: Links to inflammation and oxidative stress

Abstract

End-stage renal disease (ESRD) is characterized by a high mortality rate, derived largely from cardiovascular disease (CVD). In patients with ESRD, high levels of pro-inflammatory cytokines and increased oxidative stress are common features that may contribute to malnutrition, anaemia, recombinant human erythropoietin (rHuEPO) resistance, and atherosclerosis. Inflammation predicts poor outcome in ESRD. It is multifactorial in cause and, while it may reflect the underlying CVD, the acute-phase response may also contribute to both oxidative stress and progressive vascular injury. In patients with ESRD, the acutephase response may be influenced by a number of factors unrelated to dialysis and perhaps by the dialysis procedure itself. Inflammation and the acute-phase response interact with the haematopoietic system at several levels resulting in reduced erythropoiesis, accelerated destruction of erythrocytes, and blunting of the reactive increase in erythropoietin in response to reduced haemoglobin levels. In patients with ESRD, rHuEPO resistance has been linked with inflammation, the latter of which is often associated with a state of functional iron deficiency. Patients with ESRD are thought to have a reduced capacity to handle oxidative stress. There is recent evidence that a relationship may exist between inflammation and oxidative stress and treatment of anaemia with rHuEPO. However, iron may also generate oxidative stress. Controlled trials are needed before evidence-based recommendations for the management of inflammation-induced anaemia and resistance to rHuEPO can be defined.