Center for Laboratory Diagnostics, Primary Health Care Center, Trg Nikole Kovacevica 6, 81000, Podgorica, Montenegro.
Department of Medical Biochemistry, University of Nis - School of Medicine, Nis, Serbia.
Clin Exp Med. 2018 May;18(2):283-290. doi: 10.1007/s10238-017-0483-0. Epub 2017 Dec 6.
Xanthine oxidase (XO) is an important enzyme responsible for conversion of purine bases to uric acid and represents the major source of reactive oxygen species (ROS) production in circulation. Since pathophysiological mechanism of the relationship between XO activity and urinary albumin excretion (UAE) rate is not well elucidated, we aimed to investigate this association in patients with diabetes mellitus type 2 (DM2). In addition, we wanted to examine whether uric acid itself plays an independent role in albuminuria onset and progression, or it is only mediated through XO activity. A total of 83 patients with DM2 (of them 56.6% females) were included in this cross-sectional study. Anthropometric, biochemical parameters and blood pressure were obtained. Multivariate logistic regression analysis showed that uric acid and XO were the independent predictors for albuminuria onset in patients with DM2 [odds ratio (OR) 1.015, 95% CI (1.008-1.028), p = 0.026 and OR 1.015, 95% CI (1.006-1.026), p = 0.040, respectively]. Rise in uric acid for 1 µmol/L enhanced the probability for albuminuria by 1.5%. Also, elevation in XO activity for 1 U/L increased the probability for albuminuria for 1.5%. A total of 66.7% of variation in UAE could be explained with this Model. Both XO and uric acid are independently associated with albuminuria in diabetes. Better understanding of pathophysiological relationship between oxidative stress and albuminuria could lead to discoveries of best pharmacological treatment of XO- and/or uric acid-induced ROS, in order to prevent albuminuria onset and progression.
黄嘌呤氧化酶(XO)是一种重要的酶,负责将嘌呤碱基转化为尿酸,是循环中活性氧(ROS)产生的主要来源。由于 XO 活性与尿白蛋白排泄率(UAE)之间的病理生理机制尚未阐明,我们旨在研究 2 型糖尿病(DM2)患者中这种相关性。此外,我们还想研究尿酸本身是否在白蛋白尿的发生和进展中起独立作用,或者它只是通过 XO 活性介导的。本横断面研究共纳入 83 例 2 型糖尿病患者(其中 56.6%为女性)。测量了人体测量学、生化参数和血压。多变量逻辑回归分析显示,尿酸和 XO 是 DM2 患者白蛋白尿发生的独立预测因素[比值比(OR)1.015,95%置信区间(CI)(1.008-1.028),p=0.026 和 OR 1.015,95%CI(1.006-1.026),p=0.040]。尿酸升高 1μmol/L,白蛋白尿的发生概率增加 1.5%。XO 活性升高 1U/L,白蛋白尿的发生概率增加 1.5%。该模型可以解释 UAE 变化的 66.7%。XO 和尿酸均与糖尿病患者的白蛋白尿独立相关。更好地理解氧化应激与白蛋白尿之间的病理生理关系,可能有助于发现最佳的针对 XO 和/或尿酸诱导的 ROS 的药物治疗方法,以预防白蛋白尿的发生和进展。