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 mortality. 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 factors for inflammation, such as impure dialysate or bio‐incompatible membranes. Inflammation has recently been associated with atherosclerosis and malnutrition in ESRD, and this link has led to the development of the malnutrition, inflammation, atherosclerosis (MIA) hypothesis. This describes a syndrome whereby raised levels of pro‐inflammatory cytokines (such as IL‐1, IL‐6 and TNF‐α) are a common link between malnutrition, inflammation and atherosclerosis. Also, anaemia appears to be an important element linking elevated cytokine levels with poor patient outcomes. Several mechanisms for cytokine‐induced anaemia have been proposed, including intestinal bleeding, impaired iron metabolism and suppression of bone marrow erythropoiesis and erythropoietin production. These effects suggest that pro‐inflammatory cytokines may also be an important cause of lack of response to recombinant human erythropoietin (rh‐Epo) therapy. In the light of this putative role of pro‐inflammatory cytokines, anti‐cytokine agents may prove useful to optimize efficacy of rh‐Epo in anaemic chronic renal failure patients. Other potential therapeutic strategies include minimizing exposure to causes of inflammation from various co‐morbid conditions, such as persistent infections and chronic heart failure.