Dialysate related cytokine induction and response to recombinant human erythropoietin in haemodialysis patients
Dialysate related cytokine induction and response to recombinant human erythropoietin in haemodialysis patients
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DOI：
10.1093/ndt/15.8.1207
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发表时间：
2000-08-01
影响因子：
6.1
通讯作者：
Schiffl, H
中科院分区：
文献类型：
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作者：
Sitter, T;Bergner, A;Schiffl, H
背景。慢性炎症性疾病或感染是重组人促红细胞生成素 (rHuEpo) 反应低下的主要原因。为了检验透析液相关细胞因子诱导改变对 rHuEpo 反应的假设，我们对配对的慢性血液透析患者进行了一项前瞻性研究。我们比较了微生物质量不同的两种透析液对 rHuEpo 治疗的影响。方法。 30 名维持定期血液透析的终末期肾病男性患者被分配到使用常规（可能受到微生物污染的）透析液治疗的组（I 组）或使用在线生产的超纯透析液治疗的组（II 组）。根据维持目标血红蛋白水平 10-10.5 g/dl 所需的 rHuEpo 维持剂量对随机化进行分层。对患者进行了 12 个月的随访。 Kt/V通过Daugirdas公式计算。每周测量一次血红蛋白水平，每 6 周测量一次血清铁蛋白浓度。在研究开始时以及 3、6 和 12 个月后，通过 ELISA 测量 C 反应蛋白 (CRP) 和白细胞介素 6 (IL-6)。结果。在第一组中，连续使用碳酸氢盐透析液不会改变为达到目标血红蛋白水平而给予的rHuEpo剂量，并且与细胞因子诱导的炎症的替代标志物（CRP、IL-6）升高相关。第二组中从传统透析液改为在线生产的超纯透析液导致细菌污染减少，血液 CRP 和 IL-6 水平显着降低。伴随着rHuEpo剂量的显着和持续减少，这是纠正贫血所必需的。使用多元回归分析，IL-6 水平显示对两组中的 rHuEpo 剂量具有很强的预测价值。结论。我们的数据表明，透析液相关因素（例如低细菌污染）可诱导单核细胞活化，导致血清 IL-6 水平升高。透析相关的细胞因子诱导可能会减少红细胞生成。使用无热原超纯透析液可对 rHuEpo 产生更好的反应。它不仅可以省钱，而且还有助于维持最佳的血红蛋白水平，而无需进一步增加 rHuEpo 剂量。
Background. Chronic inflammatory disorders or infections represent a major cause of hyporesponsiveness to recombinant human erythropoietin (rHuEpo). To test the hypothesis that dialysate-related cytokine induction alters the response to rHuEpo, we conducted a prospective study with matched pairs of chronic haemodialysis patients. We compared the effect of two dialysis fluids, differing in their microbiological quality, on the rHuEpo therapy.Methods. Thirty male patients with end-stage renal disease maintained on regular haemodialysis were assigned either to a group treated with conventional (potentially microbiologically contaminated) dialysate (group I) or to a group treated with online-produced ultrapure dialysate (group II). Randomization was stratified according to the maintenance dose of rHuEpo necessary to maintain a target haemoglobin level of 10-10.5 g/dl. Patients were followed for 12 months. Kt/V was calculated by the formula of Daugirdas. Haemoglobin levels were measured weekly and serum ferritin concentrations were determined at 6-week intervals. C-reactive protein (CRP) and interleukin-6 (IL-6) was measured by an ELISA at the start of the study and after 3, 6 and 12 months.Results. In group I, continuous use of bicarbonate dialysate did not change the rHuEpo dosage given to achieve the target haemoglobin level and was associated with elevated surrogate markers (CRP, IL-6) of cytokine-induced inflammation. The switch from conventional to online-produced ultrapure dialysate in group II resulted in a lower bacterial contamination with a significant decrease of CRP and IL-6 blood levels. It was accompanied by a significant and sustained reduction of the rHuEpo dosage, which was required to correct the anaemia. Using multiple regression analysis, IL-6 levels are shown to have a strong predictive value for rHuEpo dosage in both groups.Conclusion. Our data demonstrate that dialysate-related factors such as low bacterial contamination can induce the activation of monocytes, resulting in elevated serum levels of IL-6. Dialysate-related cytokine induction might diminish erythropoiesis. The use of pyrogen free ultrapure dialysate resulted in a better response to rHuEpo. Not only would it save money, but it would also help to maintain an optimal haemoglobin level without further increase in rHuEpo dosage.