Hyporesponsiveness to erythropoietic therapy due to chronic inflammation.
The anaemia associated with chronic renal failure is multi-factorial. Although a relative erythropoietin deficiency is a major factor, it has also been recognized in recent times that uraemia is a chronic inflammatory state, and thus patients with renal failure also develop anaemia due to mechanisms associated with chronic inflammation. Thus, patients with chronic renal failure have activation of various immune cells, both monocytes and T-cells. These mononuclear cells have also been shown to release pro-inflammatory cytokines such as IL-1, IL-6, TNF-alfa and interferon gamma. These cytokines, particularly TNF-alfa and interferon gamma, are known to cause significant suppression of erythropoiesis. The exact molecular mechanism for this effect is not yet clear, but interferon gamma is an important stimulator of apoptosis in various cell types, including erythroid progenitor cells. This effect may be potentiated by other cytokines such as TNF-alfa, and this might then antagonise the anti-apoptotic action of erythropoietin on erythroid progenitors cells, thus reducing responsiveness to exogenous erythropoietic therapy. Chronic renal failure is also associated with increased hepcidin production which may also exacerbate the anaemia by inducing a functional iron deficiency in such patients.
Macdougall
I C
IC
Renal Unit, King's College Hospital, London, UK. iainc.macdougall@virgin.net
Cooper
A C
AC
D000740:Anemia / Q000188:drug therapy* / Q000209:etiology / Q000276:immunology; D002908:Chronic Disease; D016207:Cytokines / Q000276:immunology; D004920:Erythropoiesis / Q000276:immunology; D004921:Erythropoietin / Q000276:immunology / Q000627:therapeutic use*; D006801:Humans; D007249:Inflammation / Q000150:complications / Q000276:immunology*; D051437:Renal Insufficiency / Q000150:complications / Q000276:immunology*
D016207:Cytokines; D004921:Erythropoietin