Usberti Mario, Gerardi GianMario, Bufano Giuseppe, Tira Paola, Micheli Annamaria, Albertini Alberto, Floridi Ardesio, Di Lorenzo Diego, Galli Francesco
Servizio di Nefrologia e Dialisi Ospedale di Manerbio, Manerbio, Bs, Italy.
Am J Kidney Dis. 2002 Sep;40(3):590-9. doi: 10.1053/ajkd.2002.34919.
Oxidant stress has a pathogenic role in uremic anemia, possibly interfering with erythropoietin (EPO) function and red blood cell (RBC) survival. Therefore, it is expected that antioxidant therapy might exert a beneficial effect on these parameters.
To test this hypothesis, we investigated some oxidant stress indices, anemia levels, and RBC survival in 47 hemodialysis (HD) patients randomly assigned to three groups. Patients in groups A (n = l8) and B (n = 20) were on dialysis therapy using conventional cellulosic and synthetic membranes and were administered high and low doses of recombinant human EPO (rHuEPO), respectively. Patients in group C (n = 9) were dialyzed with vitamin E-modified membranes (CL-Es) and investigated in a two-step prospective study. In step Cl, patients were administered rHuEPO doses similar to those of group A. In step C2, rHuEPO doses were reduced to those of group B. As oxidant stress markers, we determined in plasma the susceptibility of lipids to undergo iron-catalyzed oxidation (reactive oxygen molecules [ROMs] test) and malondialdehyde-4-hydroxynonenal (MDA-4HNE), alpha-tocopherol (alpha-T), total thiol (-SH), and total antioxidant activity. RBC survival was measured using the chromium 51 T/2 technique in 22 patients.
Results show that: (1) high rHuEPO doses (groups A and C1) were associated with decreased ROM production, low alpha-T levels, and slightly increased -SH levels compared with corresponding groups on low rHuEPO doses (groups B and C2); (2) treatment with CL-Es (group C) increased plasma alpha-T and decreased -SH levels; these data were associated with decreased indices of lipid peroxidation, particularly MDA-4HNE 1evels, only in patients administered low rHuEPO doses; (3) alpha-T concentration influenced RBC survival, which was remarkably decreased in HD patients; patients treated with CL-Es showed a better degree of anemia correction; and (4) alpha-T level correlated negatively with -SH level and seemed to be independent of the extent of peroxidation and oxidizability of plasma lipids.
Both EPO and CL-E can influence plasma antioxidants and, to an extent, lipid peroxidation processes. However, this study shows that even in patients treated with low rHuEPO doses, RBC survival close to normal and sufficient correction of anemia are achieved only when appropriate alpha-T levels are reached.
氧化应激在尿毒症性贫血中具有致病作用，可能干扰促红细胞生成素（EPO）功能和红细胞（RBC）存活。因此，预计抗氧化治疗可能对这些参数产生有益影响。
为验证这一假设，我们在随机分为三组的47例血液透析（HD）患者中研究了一些氧化应激指标、贫血水平和RBC存活情况。A组（n = 18）和B组（n = 20）患者使用传统纤维素膜和合成膜进行透析治疗，分别给予高剂量和低剂量的重组人促红细胞生成素（rHuEPO）。C组（n = 9）患者使用维生素E修饰膜（CL-Es）进行透析，并在一项两步前瞻性研究中进行观察。在步骤C1中，给予患者与A组相似剂量的rHuEPO。在步骤C2中，将rHuEPO剂量降至B组水平。作为氧化应激标志物，我们测定了血浆中脂质对铁催化氧化的敏感性（活性氧分子[ROMs]试验）以及丙二醛-4-羟基壬烯醛（MDA-4HNE）、α-生育酚（α-T）、总巯基（-SH）和总抗氧化活性。使用铬51 T/2技术在22例患者中测量RBC存活情况。
结果显示：（1）与低剂量rHuEPO组（B组和C2组）相比，高剂量rHuEPO（A组和C1组）与ROM生成减少、α-T水平降低以及-SH水平略有升高相关；（2）使用CL-Es治疗（C组）可使血浆α-T升高，-SH水平降低；这些数据仅在给予低剂量rHuEPO的患者中与脂质过氧化指标降低相关，尤其是MDA-4HNE水平；（3）α-T浓度影响RBC存活，HD患者中RBC存活显著降低；使用CL-Es治疗的患者贫血纠正程度更好；（4）α-T水平与-SH水平呈负相关，且似乎与血浆脂质的过氧化程度和氧化能力无关。
EPO和CL-E均可影响血浆抗氧化剂，并在一定程度上影响脂质过氧化过程。然而，本研究表明，即使在低剂量rHuEPO治疗的患者中，只有达到适当的α-T水平，才能使RBC存活接近正常并充分纠正贫血。
