Usberti Mario, Gerardi Gianmario, Micheli Annamaria, Tira Paola, Bufano Giuseppe, Gaggia Paola, Movilli Ezio, Cancarini Giovanni C, De Marinis Sergio, D'Avolio Gerolamo, Broccoli Roberto, Manganoni Annunciata, Albertin Alberto, Di Lorenzo Diego
Nephrology and Dialysis Service, Manerbio Hospital, Brescia, Italy.
J Nephrol. 2002 Sep-Oct;15(5):558-64.
The oxidative damage of RBC membranes in hemodialysis (HD) patients increases red blood cell (RBC) susceptibility to hemolysis and impairs cell survival. Reduction of the oxidative stress might lead to better control of anemia and reduction of the erythropoietin (rhEPO) dose.
We studied 38 stable HD patients, given a mean dose of rhEPO of 104+/-65 U/kg BW/week, at baseline and during antioxidant treatment with either a full or a 50% dose of EPO. Antioxidant treatment involved the combined use of glutathione, GSH (1200 mg i.v. at the end of each dialysis session) and a vitamin E-bonded HD membrane, CL-E. RBC and reticulocyte counts were done monthly. RBC survival (51Cr T/2) was assayed in 18 patients before and after the end of the study. Oxidative status was determined in 10 patients by measuring plasma concentrations of malondyhaldeide-4-hydroxynonenal (MDA-4HNE), reactive oxygen molecular species (ROMs), and oxydized-LDL (oxLDL) as indices of oxidative stress, alpha-tocopherol and total thiols as single antioxidants, and TAS as a marker of total antioxidant plasma activity.
Antioxidant treatment significantly reduced the high basal plasma concentrations of MDA4HNE and oxLDL, and significantly increased those of alpha-tocopherol, whereas TAS and thiols were unmodified. These changes lasted after the reduction of EPO. Anemia significantly improved with treatment, due to a significant increase in RBC survival. A close direct linear relationship was detected between plasma levels of vitamin E and hemoglobin.
Adequate control of oxidative stress achieves better control of anemia in HD patients. Since several antioxidant systems are impaired in uremia, the combined use of the CL-E membrane and GSH seems to be the best antioxidant therapy so far, with significant saving of the rhEPO dose.
血液透析(HD)患者红细胞(RBC)膜的氧化损伤会增加红细胞对溶血的易感性并损害细胞存活。降低氧化应激可能有助于更好地控制贫血并减少促红细胞生成素(rhEPO)剂量。
我们研究了38例稳定的HD患者,在基线时以及使用全剂量或50%剂量EPO进行抗氧化治疗期间,平均rhEPO剂量为104±65 U/kg体重/周。抗氧化治疗包括联合使用谷胱甘肽(GSH,每次透析结束时静脉注射1200 mg)和维生素E结合的HD膜(CL-E)。每月进行红细胞和网织红细胞计数。在研究结束前后对18例患者进行红细胞存活(51Cr T/2)测定。通过测量血浆中丙二醛-4-羟基壬烯醛(MDA-4HNE)、活性氧分子(ROMs)和氧化型低密度脂蛋白(oxLDL)的浓度来确定10例患者的氧化状态,作为氧化应激指标,α-生育酚和总硫醇作为单一抗氧化剂,总抗氧化能力(TAS)作为血浆总抗氧化活性的标志物。
抗氧化治疗显著降低了MDA4HNE和oxLDL的高基础血浆浓度,并显著提高了α-生育酚的浓度,而TAS和硫醇未发生改变。这些变化在EPO减量后持续存在。由于红细胞存活率显著提高,治疗后贫血明显改善。检测到血浆维生素E水平与血红蛋白之间存在密切的直接线性关系。
充分控制氧化应激可更好地控制HD患者的贫血。由于尿毒症中几种抗氧化系统受损,CL-E膜和GSH联合使用似乎是迄今为止最佳的抗氧化治疗方法,可显著节省rhEPO剂量。