The Effect Of Febuxostat On Renal Function,oxidative Stress And Inflammatory Reaction In Non-dialysis Patients With Stage 2-5 Chronic Kidney Disease Complicated With Hyperuricemia

Objective:To discuss the effect of febuxostat on renal function,oxidative stress and inflammatory reaction in non-dialysis patients with stage 2-5 chronic kidney disease complicated with hyperuricemia.Methods:1、This study followed up a total of 101 patients with chronic kidney disease（CKD）stage 2-5 complicated with hyperuricemia（HUA）who met the inclusion and exclusion criteria and received the treatment of febuxostat in the Nephrology clinic or ward of our hospital from September 2020 to June 2022 as the treatment group.The standard of urate-lowering therapies（ULT）in the treatment group refers to theChinese guidelines for the diagnosis and treatment of hyperuricemia and gout.A total of 204 non-dialysis patients with CKD2-5 combined with HUA who had notpreviously received uric acid lowering therapy were collected through the information system of our hospital as a control group.In both groups,the basic medication for the treatment of chronic kidney disease was used.The changes in serum uric acid（SUA）,estimated glomerular filtration rate（e GFR）were analyzed after 6 months of febuxostat treatment,and adverse reactions during febuxostat treatment were observed.2、Among the 101 patients in the treatment group,the patients were divided into50 cases in group A（CKD stage 2-3a）and 51 cases in group B（CKD3b-5 stage）according to the e GFR before treatment,and the patients were divided into 65 cases in the standard group and 36 cases in the non-standard group according to whether the level of SUA was lower than 360μmol/L in the 6th month after febuxostat treatment.And then the changes of SUA、e GFR after 6 months of febuxostat treatment between groups A and B,and between the standard group and the non-standard group were analyzed.3、Among the 101 patients in the treatment group,a total of remaining serum in50 cases were collected in the laboratory department of our hospital before treatment and 6 months after treatment,and the high sensitivity to C-reactive protein（hs-CRP）,malondialdehyde（MDA）and superoxide dismutase（SOD）were detected.The changes of the above indexes before and after febuxostat treatment were analyzed,and the correlation between renal function and inflammatory reaction and oxidative stress response was analyzed.Results:1、There were no significant differences in gender,age,SUA,e GFR and underlying diseases between the treatment group and the control group,and between the standard group and the non-standard group（P>0.05）.There were no significant differences between group A and group B in terms of gender,age,SUA and underlying diseases（P>0.05）.2、After 6 months of febuxostat treatment,SUA decreased by an average of150.62umol/L,and the median level of e GFR increase was 4.60ml·min^-1·（1.73m²）^-1,and the difference was statistically significant compared with the control group（P<0.05）.Among them,the median level of e GFR increase was9.31ml·min^-1·（1.73m²）^-1in group A,and 2.59 ml·min^-1·（1.73m²）^-1in group B,the improvement of e GFR before and after treatment in group A was significantly higher than that in group B（P<0.05）.And the median level of e GFR increase was5.62ml·min^-1·（1.73m²）^-1in the standard group,and the e GFR was increased by an average of 4.53ml·min^-1·（1.73m²）^-1in the non-standard group,the improvement of e GFR before and after treatment in the standard group was significantly higher than that（P<0.05）.3、After 6 months of febuxostat treatment,the median level of hs-CRP decreased from 2.10mg/L to 1.26mg/L,the median level of MDA decreased from 8.47 nmol/L to 2.12 nmol/L,and the SOD level increased from 166.65 U/ml to 199.49 U/ml,all of which were statistically significant（P<0.05）.Among them,the hs-CRP reduction was1.66mg/L in the standard group and 0.82mg/L in the non-standard group,and the decrease of hs-CRP in the standard group was more obvious（P<0.05）.The MDA reduction was 5.83 nmol/L in the standard group and 1.61 nmol/L in the non-standard group,and the MDA reduction was more significant in the standard group（P<0.05）.The average increase in SOD in the standard group was 47.90 U/ml,and the average increase in SOD in the non-standard group was 33.42 U/ml,and the improvement of SOD in the standard group was more significant（P<0.05）.4、There was a negative correlation between e GFR and hs-CRP and MDA before and after febuxostat treatment,and a positive correlation with SOD.Conclusion:1、Febuxostat can effectively reduce the SUA level of non-dialysis patients with stage 2-5 chronic kidney disease complicated with hyperuricemia,improve renal function,and febuxostat has a good safety profile.2、Compared with CKD3b-5 stage patients,febuxostat can better improve the renal function of CKD2-3a patients,and urate-lowering therapy should be carried out as soon as possible.3、Controlling SUA levels below<360umol/L is more helpful to delay the progress of renal function and reduce inflammatory reaction and oxidative stress,and SUA should be actively controlled to reach the standard level.4、The levels of inflammation and oxidative stress inpatients with stage 2-5chronic kidney disease complicated with hyperuricemia after febuxostat treatment decreased significantly,and there was an inverse correlation between e GFR and inflammation and oxidative stress before and after treatment.