High blood soluble receptor p80 for tumour necrosis factor-alpha is associated with erythropoietin resistance in haemodialysis patients

Background. Inflammation is one of the major causes of resistance to erythr opoietin (rHuEpo) treatment. Tumour necrosis factor-alpha (TNF-alpha), one of the most potent proinflammatory cytokines, is known to inhibit human ery thropoiesis directly in vitro. Although blood levels of soluble receptors f or TNF-alpha (sTNFRs) are elevated in haemodialysis (HD) patients, the role of sTNFR for rHuEpo responsiveness in HD patients remains to be clarified. Methods. We measured serum sTNFR (p55 and p80) levels. in 83 stable outpati ents undergoing regular HD (age 62 +/-1, HD duration 15 +/-1 years). After dividing the patients into three groups according to rHuEpo dose: (low (L) < 60, n=31; moderate (M) greater than or equal to 60 to < 120, n=31; high ( H) greater than or equal to 120 U/kg/week rHuEpo, n=21), we examined the re lationship between serum sTNFR levels and the degree of renal anaemia and r HuEpo dosage. Results. Haemoglobin was significantly higher in patients receiving low rHu Epo dosage (L, 10.5 +/-0.2; M, 9.7 +/-0.1; H, 9.5 +/-0.2 g/dl, P <0.01 vs M and H groups). There were no differences in blood TNF-alpha, sTNFR p55, C- reactive protein, albumin, ferritin, or intact parathyroid hormone levels a mong the three groups. Body mass index and creatinine generation rate, a ma rker of whole-body muscle volume, were significantly reduced in group H (P <0.01). Serum sTNFR p80 levels were significantly higher in group H (4.88 /-0.45 ng/ml) than in L (3.73 +/-0.14 ng/ml) and M (3.67 +/-0.21 ng/ml) gro ups (P <0.05). The blood interleukin (IL)-6 level was also increased in pat ients requiring high rHuEpo doses (L, 5.5 +/-0.5; M, 6.4 +/-0.5; H, 10.2 +/ -2.0 pg/ml, P <0.05 vs L and H groups). A stepwise regression analysis reve aled that gender and sTNFR p80 were significant predictors of rHuEpo dosage . A significant direct relationship was found between rHuEpo dose and sTNFR p80 (r=0.499) and IL-6 (r=0.439) values in women (P <0.01) but not in men. Conclusions. These findings suggest that high blood sTNFR p80 may contribut e to the development of rHuEpo resistance in female patients undergoing lon g-term HD.