| Objective:To estimate the effect of the 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(SUA)and the choice of urate-lowering drugs.SUA,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 SUA,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:1.There was no significant difference in age,gender,body mass index,systolic blood pressure,diastolic blood pressure,total cholesterol,triacylglycerol,glycosylated hemoglobin,estimated glomerular filtration rate,serum creatinine,primary diseases among the three groups at baseline(P>0.050).There was no significant difference in baseline levels of SUA,inflammation and oxidative stress between group A and group B(P>0.050).The levels of SUA,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).2.After treatment for 1 month and 3 months,the values of SUA,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).3.Compared with pre-treatment period,both the SUA,hs-CRP,MDA and ET-1 levels of group A and group B were declined significantly after 3 months treatment,the changes of group A were significantly higher than those in group B[(-0.45±0.06)% vs(-0.24±0.12)%,P<0.001;(-0.70±0.20)% vs(-0.20±0.33)%,P<0.001;(-0.53±0.06)% vs(-0.23±0.06)%,P<0.001;(-0.57±0.08)% vs(-0.36±0.11)%,P<0.001,respectively].While the level of SOD had a significant rise of group A and group B after 3 months treatment,the increase of group A was significantly higher than that of group B[(0.13±0.15)% vs(0.07±0.11)%,P<0.001].After 3 months compared to baseline in group C,the values of SUA,hs-CRP and ET-1 were significantly higher(P=0.004,P<0.001,P=0.001,respectively),while the level of SOD was significantly reduced(P<0.001),and there was no significant change in MDA(P=0.819).The changes in group C were statistically different from those in group A and group B(P<0.001).4.At the end of the trial,there was no significant difference in the proportion of antioxidant drugs used by the three groups during the experiment(P>0.050).5.At baseline and 3 months after treatment,SUA was positively related to hs-CRP,MDA and ET-1,but negatively related to SOD in nonattainment group(|r|>0.50,P<0.001);SUA was positively related to hs-CRP,MDA and SOD(|r|>0.70,P<0.001),and there was no correlation between SUA and ET-1 in attainment group(P>0.050).Conclusion: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. |
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