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.
Girndt
Matthias
M
Medical Department IV, Nephrology and Hypertension Unit, University of the Saarland, D-66421 Homburg/Saar, Germany. matthias.girndt@uks.eu
Stenvinkel
Peter
P
Ulrich
Christof
C
Axelsson
Jonas
J
Nordfors
Louise
L
Barany
Peter
P
Carrero
Juan Jesus
JJ
Heine
Gunnar H
GH
Kaul
Harald
H
Köhler
Hans
H
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D004921:Erythropoietin / Q000008:administration & dosage*; D005260:Female; D006801:Humans; D016753:Interleukin-10 / Q000235:genetics*; D015850:Interleukin-6 / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D006435:Renal Dialysis
D015850:Interleukin-6; D004921:Erythropoietin; D016753:Interleukin-10