Effect of urate-lowering therapy with febuxostat on oxidative stress in hyperuricemic patients with chronic kidney disease stages 3-5 / 中华肾脏病杂志

ABSTRACT

Objective To estimate the effect of urate-lowering therapy with febuxostat on oxidative stress in chronic kidney disease (CKD) stages 3-5 patients with hyperuricemia (HUA). Methods The study was a prospective cohort study. The patients of CKD stages 3-5 with HUA between June 2015 and June 2018 in the Affiliated Hospital of Qingdao University were prospectively analyzed. The patients were assigned to febuxostat (A) group, allopurinol (B) group and non -hyperuricemia (C) group according to the level of serum uric acid and the choice of urate-loweringdrugs. Serum uric acid, hypersensitive C-reactive protein (hs-CRP), plasma malondialdehyde (MDA), superoxide dismutase (SOD) and endothelin-1 (ET-1) were measured at baseline, 1 month and 3 months after treatment and the changes of the values of inflammation and oxidative stress before or after treatment were compared. According to the level of serum uric acid, patients were divided into attainment group and nonattainment group, and the correlation between uric acid and oxidative stress was analyzed at baseline and 3 months after treatment respectively. Results There was no significant difference in baseline levels of serum uric acid, inflammation and oxidative stress between group A and group B (P>0.05). The levels of serum uric acid, hs-CRP, MDA and ET-1 of group A and group B were significantly higher than those of group C, but the level of SOD of group A and group B was significantly lower than that of group C at baseline (P<0.001). After treatment for 1 month and 3 months, the values of serum uric acid, hs-CRP, MDA and ET-1 in group A were significantly lower than those in group B, while the level of SOD in group A was significantly higher than that in group B (P<0.001). Compared with pre-treatment period, both the serum uric acid, hs-CRP, MDA and ET-1 levels of group A and group B were declined significantly while SOD had a significant rise after 3 months treatment (P<0.001). The changes of group A were significantly higher than those of group B (P<0.001). At baseline and 3 months after treatment, serum uric acid was positively related to hs-CRP, MDA and ET-1, but negatively related to SOD in nonattainment group (|r|>0.50, P<0.001);serum uric acid was positively related to hs-CRP, MDA and SOD (|r|>0.70, P<0.001), and there was no correlation between serum uric acid and ET-1 in attainment group (P>0.05). Conclusions Febuxostat performed better than allopurinol in lowering urate and inhibiting oxidative stress in CKD stages 3-5 patients with HUA, thus reducing vascular endothelial injury. Elevated serum uric acid may be one of the important factors that promote oxidative stress and increase endothelial damage in CKD patients.