Effects of urate lowering therapy with febuxostat on oxidative stress in CKD patients with hyperuricemia

Effects of urate lowering therapy with febuxostat on oxidative stress in CKD patients with hyperuricemia

LI,Qing

Department of Nephrology,the people's Hospital of Yishui,Liyi Shandong 276400,China

【Abstract】Objective:To investigate the effect of urate lowering therapy with febuxostat on the oxidative stress response in patients with chronic kidney disease(CKD)associated with hyperuricemia.Methods:A total of 106 CKD patients with hyperuricemia admitted to our hospital from May 2018 to December 2019 were enrolled and pided into control(n=53)and study(n=53)groups according to the random number table method.Among them,patients in the control group were treated with allopurinol,patients in the study group were treated with febuxostat,and patients in both groups continued treatment for 12 weeks.Serum uric acid(UA),serum creatinine(SCR),oxidative stress markers[malondialdehyde(MDA),superoxide dismutase(SOD),8-hydroxydeoxyguanosine(8-OHdG)]as well as inflammatory factors[Hypersensitivity C-Reactive Protein(hs CRP),interleukin-6(IL-6)]levels were compared between the two groups before and after treatment.Results:After treatment,UA and SCR levels in both groups were significantly lower than before treatment,and in the study group,they were significantly lower than those in the control group(P<0.05);The levels of MDA and 8-OHdG in both groups decreased significantly compared with the treatment,the levels of SOD increased significantly compared with the pretreatment,and the levels of MDA and 8-OHdG in the study group were lower than those in the control group,and the levels of SOD were higher than those in the control group(P<0.05);The levels of hs CRP and IL-6 in both groups decreased significantly compared with those before treatment,and the levels of hs CRP and IL-6 in the study group were lower than those in the control group(P<0.05).Conclusions:4>urate lowering therapy with febuxostat has precise efficacy in CKD with hyperuricemia,effectively reduces serum uric acid and creatinine levels,markedly inhibits oxidative stress responses,and reduces inflammatory factor expression.

【Key words】chronic kidney disease;Hyperuricemia;Febuxostat;Oxidative stress response

Chronic kidney disease(CKD)is a disease characterized by impaired renal function or structure,with a high incidence rate.The main manifestations of CKD are hematuria and proteinuria[1].The most common complication of CKD is hyperuricemia,which is one of the risk factors that aggravate CKD[2].The abnormal increase of serum uric acid concentration in CKD patients is easy to cause renal tubular injury,promote oxidative stress reaction and intrarenal inflammation.In clinical practice,it is usually used to treat this kind of patients by reducing uric acid symptomatically(giving allopurinol),which can alleviate the patient's condition to a certain extent,but the clinical effect is not good.In recent years,some studies have found that februstat has a more significant effect on reducing blood uric acid and can effectively delay the progression of kidney disease[3].However,at present,there are few studies on its application in patients with CKD and hyperuricemia.This study will explore the effect of fepristal hypouricemic treatment on oxidative stress response in CKD patients with hyperuricemia.The results are as follows:

1 Materials and methods

1.1 General materials

106 patients with CKD and hyperuricemia admitted to our hospital from May 2018 to December 2019 were pided into control group(n=53)and study group(n=53)by random number table method.This study was approved by the hospital ethics committee.Inclusion criteria:①clinically confirmed CKD with hyperuricemia;②No other rheumatic diseases;③Informed consent to this study.Exclusion criteria:①those with psychosis;②Those who have taken non-budestar in the past two months;③Those with important organ dysfunction;④People who are allergic to treatment drugs.There were 24 males and 29 females in the study group;The average age was(36.17±8.64)years.There were 31 males and 22 females in the control group;The average age was(37.02±8.94)years.There was no significant difference between the two groups in general data(all P>0.05),which was comparable.

1.2 Methods

The patients in the control group were treated with allopurinol(Guangdong Bidi Pharmaceutical Co.,Ltd.,GYZZ H44021368,specification:100mg/capsule),orally,100mg/time,once a day,for 24 weeks.

The patients in the study group were treated with fepristone(Hangzhou Zhuyangxin Pharmaceutical Co.,Ltd.,GYZZ H20130009,specification:40mg/capsule)orally,40mg/time,once a day,if the uric acid index after treatment is less than 360μMol/L,the drug dose was reduced to 20 mg/time,and the drug was administered continuously for 12 weeks.

1.3 Evaluation indicators

Before treatment and after 12 weeks of treatment,5ml of peripheral venous blood was taken from patients in both groups,and the bleeding serum was separated after centrifugation.Detect the level of serum uric acid(UA)and serum creatinine(Scr)of patients through automatic biochemical analyzer sunoab-1018(purchased from Shanghai Taiyi Medical Instrument and Equipment Co.,Ltd.);The level of malondialdehyde(MDA)was measured by thiobarbituric acid reaction;The level of superoxide dismutase(SOD)was measured by xanthine oxidase colorimetry;The levels of 8-hydroxydeoxyguanosine(8-OHdG),hypersensitive C-reactive protein(hs-CRP)and interleukin-6(IL-6)were measured by enzyme-linked immunosorbent assay.

1.4 Statistical methods

The data in this study were analyzed and processed by SPSS 22.0 software.When P<0.05,the difference was considered statistically significant.Oxidative stress response index and other measurement data are expressed in(±s),and t-test is adopted;The count data is expressed in%,usingχ2 Inspection.

2 Results

2.1 comparison of UA and SCR levels before and after treatment between the two groups

Before treatment, there was no significant difference in the levels of UA and SCR between the two groups (P > 0.05); After treatment, UA and SCR levels were significantly decreased in both groups, and were significantly lower in the study group than in the control group (P < 0.05). See Table 1.

Table 1 Comparison of UA and Scr levels before and after treatment between the two groups(

±s)

Note:Compared with the same group before treatment,*P<0.05

2.2 comparing the levels of oxidative stress indicators between the two groups before and after treatment

Before treatment, there were no significant differences in the levels of MDA, SOD and 8-OHdG between the two groups (P > 0.05); After treatment, the levels of MDA and 8-OHdG in both groups were significantly decreased, and the levels of SOD were significantly increased, and the levels of MDA and 8-OHdG in the study group were lower than those in the control group, while the levels of SOD were higher than those in the control group (P < 0.05). See Table 2.

Table 2 Comparison of oxidative stress index levels before and after treatment between the two groups(±s)

Note:Compared with the same group before treatment,*P<0.05

2.3 comparing the levels of inflammatory factors before and after treatment between the two groups

Before treatment, there was no significant difference in hs CRP and IL-6 levels compared with the other two groups (P > 0.05); After treatment, the levels of hs CRP and IL-6 in both groups decreased significantly, and the levels of the above indicators in the study group were lower than those in the control group (P < 0.05). See Table 3.

Table 3 Comparison of the levels of inflammatory factors between the two groups before and after treatment(±s)

Note:Compared with the same group before treatment,*P<0.05

3 Discussion

The most common complication of CKD is hyperuricemia,which will seriously affect the development of CKD[4].In clinical practice,patients are usually given oral allopurinol for symptomatic treatment,which can alleviate the condition of patients to a certain extent,but there are limitations such as drug intolerance,and the clinical efficacy of patients is not ideal.Some studies have shown that oxidative stress plays an important role in the occurrence and development of CKD with hyperuricemia[5].Therefore,inhibition of oxidative stress response has become one of the key points in the treatment of such patients.

Non-bulinastatin is a xanthine oxidase inhibitor,which can inhibit the synthesis of uric acid by selectively inhibiting the xanthine oxidase,thereby reducing the effect of serum uric acid.Non-bulinastatin synthetic drug-enzyme complex is relatively stable,and will not have other effects on other enzymes.Most of them are not excreted by the kidney,and have no obvious adverse effects on the body,with good safety[6].

Hyperuricemia is mainly a state of the body caused by high uric acid in the blood,while Scr is mainly discharged from the body by glomerular filtration.Measuring its level can directly reflect the patient's renal function[7].The results of this study showed that after treatment,the levels of UA and Scr in the two groups were significantly lower than those before treatment,and the study group was significantly lower than the control group.The results showed that the treatment of hyperuricemia associated with CKD by feprista can further reduce the level of serum uric acid and creatinine,and improve the condition of patients.Febuprista can inhibit oxidative and reduced xanthine oxidase,and the compound produced by its combination has high stability,which can effectively and continuously inhibit the synthesis of UA,thereby alleviating the patient's condition and improving renal function

[8].

Relevant studies have found that hyperuricemia can cause urinary protein and kidney damage,which may be related to the activation of oxidative stress response[9].Among the oxidative stress indicators,MDA is the final product of peroxide reaction,and the concentration of this indicator can reflect the oxidative stress of human body;SOD can eliminate oxygen free radicals in the body,which is beneficial to the anti-aging of the body;8-OHdG is an oxidative adduct that can cause DNA damage.In this study,after treatment,the level of MDA and 8-OHdG in the study group was lower than that in the control group,while the level of SOD was higher than that in the control group.These results suggest that fepristal hypouricemic treatment can significantly inhibit oxidative stress in patients with CKD and hyperuricemia.CKD patients with hyperuricemia will induce oxidative stress reaction,activate inflammatory pathway and promote the synthesis of pro-inflammatory factors(hs-CRP,IL-6,etc.)[10]because the cellular mechanism needs to balance the intracellular concentration of uric acid.Therefore,the level of serum inflammatory factors in patients is closely related to oxidative stress.This study further analyzed the level of serum inflammatory factors in patients.The results showed that after treatment,the average level of hs-CRP and IL-6 in the study group was significantly lower than that in the control group.It can be seen that fepristone can further reduce the expression of inflammatory factors.This may be related to the selective inhibition of xanthine oxidase,the high efficiency and sustained inhibition of the synthesis of uric acid in patients'blood,the improvement of the degree of endothelial injury,and the significant inhibition of oxidative stress.

To sum up,febuprista has a definite effect on reducing uric acid in the treatment of CKD with hyperuricemia.It can effectively reduce the levels of serum uric acid and creatinine,significantly inhibit oxidative stress reaction,and reduce the expression of inflammatory factors.

Reference

[1]Bian Zhixiang,Gu Huiyi,Chen Peihua Observation on the curative effect of nephritis rehabilitation tablets combined with fepristal tablets in the treatment of chronic kidney disease with hyperuricemia[J]Chinese Journal of Integrated Traditional and Western Medicine Nephropathy,2018,019(012):1097-1099.

[2]Gong Shuhao,Lu Wanjun,Ouyang Liurong,etc Meta-analysis of the efficacy and effect of feprista on renal function in patients with chronic kidney disease and hyperuricemia[J]Tianjin Pharmaceutical,2018,046(010):1102-1107.

[3]Song Liuquan,Tan Huanyuan,Xie Baochao,etc Analysis of the application value of feprista in the treatment of chronic kidney disease with hyperuricemia[J]Shandong Pharmaceutical,2019,59(14):60-62.

[4]Zhang Hao,Pan Binbin,Fan Li,etc Analysis of the characteristics of hyperuricemia in non-dialysis patients with chronic kidney disease[J]Journal of Clinical Nephrology,2018,018(010):620-623634.

[5]Zhang Xiaoxiao,Che Lin,Zhang Hui,Wang Yanfei,et al.Non-bulinastatin inhibits oxidative stress in patients with chronic kidney disease in stage 3-5 and hyperuricemia[J].Chinese Journal of Kidney Disease,2019(09):676-683.

[6]Tan Zhao,Li Wenge Renal protective effect of feprista in patients with chronic kidney disease and hyperuricemia:a randomized controlled study[J]Journal of Fujian Medical University,2019,53(01):32-37.

[7]Zhang Jing Analysis of serum uric acid level and influencing factors in patients with chronic kidney disease in stage 3 to 5[J]Journal of Clinical Nephrology,2018,018(009):521-525.

[8]Wang Xin,Gao Bihu,Zhang Yanan,Yin Yutong,Jia Panpan,Li Suhua.The effect of allopurinol combined with fepristone on uric acid level and renal function in patients with hyperuricemic chronic kidney disease[J].Chinese Journal of Clinical Pharmacology,2019,35(18):2040-2042+2050.

[9]Xiao Lan,Li Jiangtao,Li Qiang,etc The effect of fepristone on serum SUA level and oxidative stress in patients with acute gouty arthritis[J]Progress in Modern Biomedicine,2018,018(008):1548-1551.

[10]Wei Xiaoyan,Li Yingjie,Zhao Xuehui,etc Observation on the effect of different doses of feprista in the treatment of hyperuricemia with gout and its effect on inflammatory factors and vascular endothelial injury factors[J]Clinical misdiagnosis and mistreatment,2019,32(10):27-32.