Influence of cytokine gene polymorphisms on erythropoetin dose requirements in chronic haemodialysis patients

Background. Chronic inflammation influences renal anaemia and reduce erythropoetin effectiveness. Chronic kidney disease and haemodialysis (HD) induce elevated cytokine and C-reactive protein (CRP) levels at an inter-individually variable extent. These differences are in part due to polymorphisms within cytokine genes, e.g. for pro-inflammatory interleukin-6 (IL-6) and anti-inflammatory interleukin-10 (IL-10). We hypothesized that these polymorphisms influence erythropoetin effectiveness. Methods. Genotyping for polymorphisms of IL-6 (174G/C) and IL-10 (1082G/A) genes was done in 460 prevalent HD patients. Erythropoetin requirements were determined after three months of stable dosing of erythropoesis stimulating proteins (ESP). The effect of the cytokine genotypes was evaluated by multiple regression analysis. Results. The presence of the IL-6 174G allele (found to be related with higher secretion of IL-6) was associated with a 26 higher ESP dose compared with individuals without the G allele (P = 0.008). The IL-10 1082 G/A polymorphism was not associated with ESP needs. Multivariate analysis detected a predictive value for ESP dose of the IL-6 polymorphism (P = 0.022), the haemoglobin level and the dose of i.v. iron, but not of age, gender, dialysis vintage, ferritin or the CRP value. Conclusions. Presence of the IL-6 allele 174G is related to higher ESP doses in chronic HD patients. The polymorphism of the anti-inflammatory IL-10 does not influence ESP dose, probably due to the fact that this cytokine has directly inhibitory effects on haematopoiesis in addition to its beneficial effects on inflammation.