血液透析患者中高浓度的肿瘤坏死因子-α可溶性受体p80与促红细胞生成素抵抗相关。
High blood soluble receptor p80 for tumour necrosis factor-alpha is associated with erythropoietin resistance in haemodialysis patients.
作者信息
Kato A, Odamaki M, Takita T, Furuhashi M, Maruyama Y, Hishida A
机构信息
First Department of Medicine, Hamamatsu University School of Medicine, 1-20-1 Handayama, Hamamatsu 431-3192, Japan.
出版信息
Nephrol Dial Transplant. 2001 Sep;16(9):1838-44. doi: 10.1093/ndt/16.9.1838.
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.
背景
炎症是促红细胞生成素（rHuEpo）治疗抵抗的主要原因之一。肿瘤坏死因子-α（TNF-α）是最有效的促炎细胞因子之一，已知其在体外可直接抑制人类红细胞生成。尽管血液透析（HD）患者中可溶性TNF-α受体（sTNFRs）水平升高，但sTNFR在HD患者对rHuEpo反应性中的作用仍有待阐明。
方法
我们测量了83例接受定期HD的稳定门诊患者（年龄62±1岁，HD病程15±1年）的血清sTNFR（p55和p80）水平。根据rHuEpo剂量将患者分为三组：（低剂量组（L）<60，n = 31；中剂量组（M）≥60至<120，n = 31；高剂量组（H）≥120 U/kg/周rHuEpo，n = 21），我们研究了血清sTNFR水平与肾性贫血程度及rHuEpo剂量之间的关系。
结果
接受低剂量rHuEpo的患者血红蛋白水平显著更高（L组，10.5±0.2；M组，9.7±0.1；H组，9.5±0.2 g/dl，与M组和H组相比P<0.01）。三组之间血液TNF-α、sTNFR p55、C反应蛋白、白蛋白、铁蛋白或完整甲状旁腺激素水平无差异。H组的体重指数和肌酐生成率（全身肌肉量的标志物）显著降低（P<0.01）。H组血清sTNFR p80水平（4.88±0.45 ng/ml）显著高于L组（3.73±0.14 ng/ml）和M组（3.67±0.21 ng/ml）（P<0.05）。需要高剂量rHuEpo的患者血液白细胞介素（IL）-6水平也升高（L组，5.5±0.5；M组，6.4±0.5；H组，10.2±2.0 pg/ml，与L组和M组相比P<0.05）。逐步回归分析显示，性别和sTNFR p80是rHuEpo剂量的显著预测因素。在女性中，rHuEpo剂量与sTNFR p80（r = 0.499）和IL-6（r = 0.439）值之间存在显著的直接关系（P<0.01），而在男性中则不存在。
结论
这些发现表明，高血液sTNFR p80可能导致长期HD女性患者对rHuEpo产生抵抗。
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