The role of inflammation in the anaemia of end-stage renal disease

Chronic inflammation is a common feature of end-stage renal disease (ESRD) that is gaining increasing attention as a major cause of morbidity and mort ality. It is well established that ESRD per se carries a heightened risk of inflammatory disorders and other co-morbid conditions, but it should also be pointed out that dialysis treatment per se can bring additional risk fac tors for inflammation, such as impure dialysate or bio-incompatible membran es. Inflammation has recently been associated with atherosclerosis and maln utrition in ESRD, and this link has led to the development of the malnutrit ion, inflammation, atherosclerosis (MIA) hypothesis. This describes a syndr ome whereby raised levels of pro-inflammatory cytokines (such as IL-1, IL-6 and TNF-alpha) are a common link between malnutrition, inflammation and at herosclerosis. Also, anaemia appears to be an important element linking ele vated cytokine levels with poor patient outcomes. Several mechanisms for cy tokine-induced anaemia have been proposed, including intestinal bleeding, i mpaired iron metabolism and suppression of bone marrow erythropoiesis and e rythropoietin production. These effects suggest that pro-inflammatory cytok ines may also be an important cause of lack of response to recombinant huma n erythropoietin (rh-Epo) therapy. In the light of this putative role of pr o-inflammatory cytokines, anticytokine agents may prove useful to optimize efficacy of rh-Epo in anaemic chronic renal failure patients. Other potenti al therapeutic strategies include minimizing exposure to causes of inflamma tion from various co-morbid conditions, such as persistent infections and c hronic heart failure.