Plasma Xanthine Oxidase Activity Is Predictive of Cardiovascular Disease in Patients with Chronic Kidney Disease, Independently of Uric Acid Levels
Plasma Xanthine Oxidase Activity Is Predictive of Cardiovascular Disease in Patients with Chronic Kidney Disease, Independently of Uric Acid Levels
复制标题
DOI：
10.1159/000441091
复制
发表时间：
2015-01-01
期刊：
影响因子：
2.5
通讯作者：
Dussol, Bertrand
中科院分区：
文献类型：
--
作者：
Gondouin, Bertrand;Jourde-Chiche, Noemie;Dussol, Bertrand
背景：慢性肾脏病（CKD）与心血管疾病发病率和死亡率增加有关。氧化应激似乎在此过程中发挥了关键作用，嘌呤代谢可能参与了CKD相关的氧化应激。黄嘌呤氧化酶（XO）是一种参与嘌呤代谢的酶，也负责活性氧的产生。研究方法：本前瞻性研究旨在分析非糖尿病CKD 3-5期或长期血液透析（HD）患者中参与氧化还原平衡、嘌呤代谢和心血管事件的分子的血浆剂量之间的关系。将CKD（n = 51）和HD（n = 50）患者与匹配的健康对照（n = 38）进行比较，并随访3年。结果：CKD和HD患者血浆抗氧化剂（硒、锌、维生素C）水平均降低。HD患者的抗氧化酶超氧化物歧化酶水平降低，氧化产物（缺血修饰白蛋白，丙二醛[MDA]）水平升高。HD队列中参与嘌呤代谢的以下底物和酶升高：腺苷、腺苷脱氨酶和促氧化剂XO。XO活性与超氧化物歧化酶呈负相关，与丙二醛呈正相关。有趣的是，无论尿酸水平如何，XO活性都是CKD和HD患者心血管事件的独立预测因子。尿酸不能预测事件。结论：这突出了XO本身在CKD相关心血管疾病（CVD）中的可能作用，并提出了一个假设，即XO抑制剂对CKD中CVD的有益作用也可能是由于氧化应激的减少。(C)2015 S. Karger AG，巴塞尔
Background: Chronic kidney disease (CKD) is associated with increased cardiovascular morbidity and mortality. Oxidative stress seems to play a pivotal role in this process, and purine metabolism may be involved in CKD-related oxidative stress. Xanthine oxidase (XO) is an enzyme involved in purine metabolism and is also responsible for the production of reactive oxygen species. Methods: This prospective study aimed to analyze the relation between plasma dosages of molecules involved in redox balance, purine metabolism and cardiovascular events in patients with non-diabetic CKD stages 3-5 or on chronic hemodialysis (HD). CKD (n = 51) and HD (n = 50) patients were compared to matched healthy controls (n = 38) and followed-up for 3 years. Results: Both CKD and HD patients had decreased plasma levels of antioxidants (selenium, zinc, vitamin C). HD patients had decreased levels of the antioxidant enzyme superoxide dismutase and increased levels of oxidation products (ischemia-modified albumin, malondialdehyde [MDA]). The following substrates and enzymes involved in purine metabolism were increased in the HD cohort: adenosine, adenosine deaminase and the pro-oxidant XO. XO activity was negatively correlated with super oxide dismutase and positively with MDA. Interestingly, XO activity was an independent predictor of cardiovascular events in CKD and HD patients, regardless of uric acid levels. Uric acid was not predictive of events. Conclusion: This highlights a possible role of XO itself in CKD-related cardiovascular disease (CVD) and raises the hypothesis that beneficial effects observed with XO inhibitors on CVD in CKD may also be due to the reduction of oxidative stress. (C) 2015 S. Karger AG, Basel