Fassett Robert G, Robertson Iain K, Ball Madeleine J, Geraghty Dominic P, Coombes Jeff S
School of Human Movement Studies, The University of Queensland, Brisbane, Queensland, Australia.
School of Human Life Sciences, University of Tasmania, Launceston, Tasmania, Australia.
Nephrology (Carlton). 2015 Oct;20(10):697-705. doi: 10.1111/nep.12502.
Statins have pleiotropic effects that include attenuation of oxidative stress that may be relevant for chronic kidney disease (CKD) patients. We investigated the effect of long-term atorvastatin therapy on oxidative stress biomarkers in CKD patients.
This was a pre-specified secondary analysis of data from a randomized, double-blind, placebo-controlled trial (Lipid lowering and Onset of Renal Disease, LORD) in CKD patients. Participants received 10 mg/day atorvastatin (n = 47) or placebo (n = 39) for 3 years. Plasma measures (total F2-isoprostanes, malondialdehyde. protein carbonyls, uric acid, glutathione peroxidase (GPx) activity and total antioxidant capacity (TAC) ) were performed at baseline and at 3 years. Age and sex matched participants (n = 34) with normal kidney function were controls.
CKD patients had significantly (P < 0.05) increased F2-isoprostanes and uric acid and decreased GPx activity compared with controls. When comparing the treatment (atorvastatin (A) vs placebo (P) ) change from baseline to 3 years, there were no significant differences (P > 0.05) in the group difference of the change values: (mean (95% CI), F2-isoprostanes = 5.3 (-29.2 to 39.8) pg/mL, protein carbonyls = 0.03 (-0.13 to 0.19) nmol/mg, GPx activity = -0.10 (-4.73 to 4.52) (U/L), uric acid = 8.8 (-33.9 to 51.6) μmol/L or TAC = -0.03 (-0.10 to 0.04) mmol/L. A significant difference (P = 0.04) in the change in malondialdehyde between groups, 1.52(0.09 to 2.96) μmol/L, was due to a large decrease in the placebo group.
CKD patients had elevated oxidative stress that was not attenuated by atorvastatin 10 mg/day for 3 years.
他汀类药物具有多效性作用，其中包括减轻氧化应激，这可能与慢性肾脏病（CKD）患者相关。我们研究了长期阿托伐他汀治疗对CKD患者氧化应激生物标志物的影响。
这是一项对CKD患者进行的随机、双盲、安慰剂对照试验（脂质降低与肾病发病，LORD）数据的预先指定的二次分析。参与者接受10毫克/天的阿托伐他汀（n = 47）或安慰剂（n = 39）治疗3年。在基线和3年时进行血浆检测（总F2-异前列腺素、丙二醛、蛋白质羰基、尿酸、谷胱甘肽过氧化物酶（GPx）活性和总抗氧化能力（TAC））。年龄和性别匹配的肾功能正常的参与者（n = 34）作为对照。
与对照组相比，CKD患者的F2-异前列腺素和尿酸显著升高（P < 0.05），GPx活性降低。比较从基线到3年的治疗（阿托伐他汀（A）与安慰剂（P））变化时，变化值的组间差异无显著差异（P > 0.05）：（均值（95%可信区间），F2-异前列腺素 = 5.3（-29.2至39.8）皮克/毫升，蛋白质羰基 = 0.03（-0.13至0.19）纳摩尔/毫克，GPx活性 = -0.10（-4.73至4.52）（单位/升），尿酸 = 8.8（-33.9至51.6）微摩尔/升或TAC = -0.03（-0.10至0.04）毫摩尔/升。两组间丙二醛变化存在显著差异（P = 0.04），为1.52（0.09至2.96）微摩尔/升，这是由于安慰剂组大幅下降所致。
CKD患者氧化应激升高，每日10毫克阿托伐他汀治疗3年未使其减轻。
