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

摘要

BACKGROUND: Inflammation is one of the major causes of resistance to erythropoietin (rHuEpo) treatment. Tumour necrosis factor-alpha (TNF-alpha), one of the most potent proinflammatory cytokines, is known to inhibit human erythropoiesis directly in vitro. Although blood levels of soluble receptors for 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 outpatients 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) > or =60 to <120, n=31; high (H) > or =120 U/kg/week rHuEpo, n=21), we examined the relationship between serum sTNFR levels and the degree of renal anaemia and rHuEpo dosage. RESULTS: Haemoglobin was significantly higher in patients receiving low rHuEpo 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 among the three groups. Body mass index and creatinine generation rate, a marker 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) groups (P<0.05). The blood interleukin (IL)-6 level was also increased in patients 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 revealed 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 contribute to the development of rHuEpo resistance in female patients undergoing long-term HD.