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铁调素不能作为维持性红细胞生成刺激剂治疗的血液透析患者铁需求的生物标志物。

Hepcidin is not useful as a biomarker for iron needs in haemodialysis patients on maintenance erythropoiesis-stimulating agents.

机构信息

Hemodialysis Unit Ospedale Policlinico, Division of Nephrology, University of Verona, Verona, Italy.

出版信息

Nephrol Dial Transplant. 2010 Dec;25(12):3996-4002. doi: 10.1093/ndt/gfq321. Epub 2010 Jun 10.

DOI:10.1093/ndt/gfq321
PMID:20538788
Abstract

BACKGROUND

It has been suggested that hepcidin may be useful as a tool for managing iron therapy in haemodialysis (HD) patients on erythropoiesis-stimulating agents (ESA).

METHODS

We used SELDI-TOF mass spectrometry assay to measure serum hepcidin-25 (Hep-25) and hepcidin-20 (Hep-20) in 56 adult HD patients on maintenance ESA to assess their ability to predict haemoglobin (Hb) response after 1 g intravenous iron (62.5 mg ferric gluconate at 16 consecutive dialysis sessions) and their relationship with markers of iron status, inflammation and erythropoietic activity.

RESULTS

At multivariate analysis (in a model that also included Hb, reticulocyte, ESA dose, HFE genotype, soluble transferrin receptor [sTfR] and C-reactive protein), Hep-25 independently correlated with ferritin (β = 0.03, P = 0.01) and the percentage of hypochromic red blood cells [%Hypo] (β = 1.84, P = 0.01), suggesting that Hep-25 may be a useful biomarker for iron stores and bone marrow iron availability. Hep-20 correlated independently with Hep-25 (β = 0.159, P < 0.001) and ferritin (β = 0.006, P = 0.05), suggesting that it may be a useful additional biomarker for iron stores. On receiver operating characteristics curve analysis, neither Hep-25 nor Hep-20 significantly predicted who will increase their Hb after iron loading (AUC = 0.52 ± 0.09 and 0.54 ± 0.08, P = 0.612), and the same applied to ferritin and transferrin saturation (AUC = 0.55 ± 0.08 and 0.59 ± 0.08, P = 0.250), whereas %Hypo and reticulocyte Hb content were significant predictors (AUC = 0.84 ± 0.05 and 0.70 ± 0.08, P < 0.01). At multivariate logistic regression analysis, %Hypo was the only biomarker independently associated with iron responsiveness.

CONCLUSIONS

Although our study suggests an important role for hepcidin in regulating iron homeostasis in HD patients on ESA, our findings do not support its utility as a predictor of iron needs, offering no advantage over established markers of iron status.

摘要

背景

有研究表明,铁调素(hepcidin)可能是一种有用的工具,可用于管理接受促红细胞生成素刺激剂(ESA)治疗的血液透析(HD)患者的铁治疗。

方法

我们使用 SELDI-TOF 质谱分析测定 56 名接受 ESA 维持治疗的成年 HD 患者的血清铁调素-25(Hep-25)和铁调素-20(Hep-20),以评估它们预测 1 g 静脉铁(16 次连续透析时给予 62.5 mg 葡聚糖铁)后血红蛋白(Hb)反应的能力,并评估它们与铁状态、炎症和红细胞生成活性标志物的关系。

结果

在多变量分析(模型中还包括 Hb、网织红细胞、ESA 剂量、HFE 基因型、可溶性转铁蛋白受体[sTfR]和 C 反应蛋白)中,Hep-25 与铁蛋白(β = 0.03,P = 0.01)和低色素红细胞百分比[%Hypo](β = 1.84,P = 0.01)独立相关,提示 Hep-25 可能是铁储存和骨髓铁利用的有用生物标志物。Hep-20 与 Hep-25 (β = 0.159,P < 0.001)和铁蛋白(β = 0.006,P = 0.05)独立相关,提示它可能是铁储存的另一个有用的附加生物标志物。在接受者操作特征曲线分析中,Hep-25 和 Hep-20 均不能显著预测铁负荷后 Hb 升高的患者(AUC = 0.52 ± 0.09 和 0.54 ± 0.08,P = 0.612),铁蛋白和转铁蛋白饱和度也是如此(AUC = 0.55 ± 0.08 和 0.59 ± 0.08,P = 0.250),而%Hypo 和网织红细胞 Hb 含量是显著的预测因子(AUC = 0.84 ± 0.05 和 0.70 ± 0.08,P < 0.01)。在多变量逻辑回归分析中,%Hypo 是唯一与铁反应性独立相关的生物标志物。

结论

尽管我们的研究表明铁调素在调节接受 ESA 治疗的 HD 患者的铁稳态方面具有重要作用,但我们的研究结果并不支持其作为铁需求预测因子的效用,也没有优于现有的铁状态标志物。

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