Tarng Der-Cherng, Hung Szu-Chun, Huang Tung-Po
National Yang-Ming University School of Medicine, and Division of Nephrology, Department of Medicine, Taipei Veterans General Hospital, 201, Section 2, Shih-Pai Road, Taipei 112, Taiwan.
J Am Soc Nephrol. 2004 Sep;15(9):2486-93. doi: 10.1097/01.ASN.0000137884.59308.E7.
Intravenous ascorbic acid (IVAA) medication has been shown to facilitate iron release from inert depots and subsequently circumvent the defective iron utilization in chronic hemodialysis (HD) patients who are treated with recombinant human erythropoietin (rHuEPO). This study focuses on the effects of IVAA supplementation on serum concentrations of soluble transferrin receptors (TfR) on the basis of the hypothesis that an increase of labile iron in the cytosol will lead to inhibition of TfR expression. First, 138 HD patients were studied to evaluate the interrelation between serum TfR and iron status. In a stepwise multivariate analysis, serum EPO and transferrin saturation (TSAT) were the two independent predictors for serum TfR in HD patients (r(2) = 0.510, P < 0.001). Further analyses showed that the lower the serum EPO and the higher the TSAT, the lower the serum TfR in HD patients who are on maintenance rHuEPO treatment. Second, 36 HD patients were recruited in a randomized, controlled study to receive IVAA (total dose of 2000 mg) or normal saline (placebo) medication. Serum levels of TfR, EPO, and ferritin and TSAT were measured at baseline and within 7 d after starting IVAA or placebo. There were no significant changes in serum EPO and ferritin levels in patients who received either IVAA (n = 18) or placebo (n = 18). Serum TfR levels (P < 0.001) significantly declined with a parallel rise in TSAT (P < 0.05) as compared with presupplemental values within 7 d in IVAA patients before any apparent alteration in hematocrit values, but the changes were not observed in the placebo group. The trend of decreased serum TfR and increased TSAT was similar in IVAA patients with ferritin of <500 microg/L or >500 microg/L. It is concluded that ascorbic acid status can significantly decrease serum TfR concentrations and increase percentage of TSAT, probably through alterations in intracellular iron metabolism.
静脉注射抗坏血酸（IVAA）已被证明有助于从惰性储存库中释放铁，并随后规避接受重组人促红细胞生成素（rHuEPO）治疗的慢性血液透析（HD）患者中存在的铁利用缺陷。本研究基于胞质中不稳定铁增加会导致转铁蛋白受体（TfR）表达受抑制这一假设，重点关注补充IVAA对血清可溶性转铁蛋白受体（TfR）浓度的影响。首先，对138例HD患者进行研究以评估血清TfR与铁状态之间的相互关系。在逐步多变量分析中，血清促红细胞生成素（EPO）和转铁蛋白饱和度（TSAT）是HD患者血清TfR的两个独立预测因子（r² = 0.510，P < 0.001）。进一步分析表明，在接受维持性rHuEPO治疗的HD患者中，血清EPO越低且TSAT越高，血清TfR越低。其次，36例HD患者被纳入一项随机对照研究，接受IVAA（总剂量2000 mg）或生理盐水（安慰剂）治疗。在基线以及开始IVAA或安慰剂治疗后7天内，测量TfR、EPO、铁蛋白和TSAT的血清水平。接受IVAA（n = 18）或安慰剂（n = 18）的患者血清EPO和铁蛋白水平均无显著变化。与补充前值相比，IVAA患者在血细胞比容值出现任何明显变化之前的7天内，血清TfR水平显著下降（P < 0.001），同时TSAT平行升高（P < 0.05），但安慰剂组未观察到这些变化。铁蛋白<500 μg/L或>500 μg/L的IVAA患者中，血清TfR降低和TSAT升高的趋势相似。得出的结论是，抗坏血酸状态可能通过改变细胞内铁代谢，显著降低血清TfR浓度并提高TSAT百分比。
