Morimoto Hisanori, Nakao Kazushi, Fukuoka Kousuke, Sarai Ai, Yano Ai, Kihara Takashi, Fukuda Shinji, Wada Jun, Makino Hirofumi
Department of Medicine and Clinical Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1, Shikata-cho, Okayama 700-8558, Japan.
Nephrol Dial Transplant. 2005 Dec;20(12):2775-82. doi: 10.1093/ndt/gfi121. Epub 2005 Oct 12.
Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of nitric oxide synthase and an independent predictor of overall mortality and cardiovascular outcome in haemodialysis (HD) patients. In the present study, we compared the effects of a vitamin E-coated polysulfone membrane (PSE) and a non-vitamin E-coated polysulfone membrane (PS) on oxidative stress markers such as ADMA.
Thirty-one HD patients were enrolled to this investigation. They were allocated into two groups: in the PSE group (n = 16), PSE was used for 6 months, followed by PS for an additional 12 months; in the PS group (n = 15), PS was used for the entire observation period. Plasma ADMA, oxidized low density lipoprotein (Ox-LDL) and malondialdehyde LDL (MDA-LDL) levels were measured at baseline, 3, 6, 12 and 18 months. Plasma ADMA in peritoneal dialysis (PD) patients and in healthy individuals was also measured.
Predialysis concentrations of ADMA (0.72+/- 0.13 nmol/ml) were significantly higher in the HD group than in both PD patients (0.63+/-0.10 nmol/ml, P<0.01) and healthy individuals (0.44+/-0.01 nmol/ml, P<0.0001). Treatment with PSE for 6 months significantly reduced predialysis levels of ADMA (0.54+/-0.09 nmol/ml) compared with baseline (0.74+/-0.12 nmol/ml; P<0.01). Predialysis levels of Ox-LDL and MDA-LDL after 6 months therapy with PSE were also significantly lower than baseline values. Treatment with PS subsequent to treatment with PSE again increased ADMA, Ox-LDL and MDA-LDL back to baseline levels. In the PS group, ADMA, Ox-LDL and MDA-LDL levels remained unchanged during the entire treatment period of 18 months.
We confirmed that use of PSE reduced ADMA that had accumulated in HD patients. This finding indicates that PSE exerts anti-oxidant activity. A randomized controlled study will be required to determine whether PSE prevents cardiovascular diseases and other dialysis-related complications by reducing oxidative stress.
不对称二甲基精氨酸（ADMA）是一氧化氮合酶的内源性抑制剂，也是血液透析（HD）患者全因死亡率和心血管结局的独立预测因子。在本研究中，我们比较了维生素E涂层聚砜膜（PSE）和非维生素E涂层聚砜膜（PS）对ADMA等氧化应激标志物的影响。
31例HD患者纳入本研究。他们被分为两组：PSE组（n = 16），使用PSE 6个月，随后使用PS再治疗12个月；PS组（n = 15），在整个观察期使用PS。在基线、3、6、12和18个月时测量血浆ADMA、氧化型低密度脂蛋白（Ox-LDL）和丙二醛修饰的低密度脂蛋白（MDA-LDL）水平。还测量了腹膜透析（PD）患者和健康个体的血浆ADMA水平。
HD组透析前ADMA浓度（0.72±0.13 nmol/ml）显著高于PD患者（0.63±0.10 nmol/ml，P<0.01）和健康个体（0.44±0.01 nmol/ml，P<0.0001）。与基线（0.74±0.12 nmol/ml；P<0.01）相比，使用PSE治疗6个月可显著降低透析前ADMA水平（0.54±0.09 nmol/ml）。PSE治疗6个月后，透析前Ox-LDL和MDA-LDL水平也显著低于基线值。PSE治疗后使用PS再次使ADMA、Ox-LDL和MDA-LDL升高至基线水平。在PS组中，ADMA、Ox-LDL和MDA-LDL水平在18个月的整个治疗期间保持不变。
我们证实使用PSE可降低HD患者体内蓄积的ADMA。这一发现表明PSE具有抗氧化活性。需要进行一项随机对照研究来确定PSE是否通过降低氧化应激来预防心血管疾病和其他透析相关并发症。
