Abstract
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.
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This work was financially supported in part by a grant from the Ministry of Education, Science and Technological Development, Republic of Serbia (Project Number 175035).
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The study protocol was approved by the Ethical Committee of Primary Health Care Center in Podgorica, Montenegro, and the research was carried out in compliance with the Declaration of Helsinki.
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Klisic, A., Kocic, G., Kavaric, N. et al. Xanthine oxidase and uric acid as independent predictors of albuminuria in patients with diabetes mellitus type 2. Clin Exp Med 18, 283–290 (2018). https://doi.org/10.1007/s10238-017-0483-0
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DOI: https://doi.org/10.1007/s10238-017-0483-0