| Objective: To compare the uric acid lowering efficacy of febuxostat,benzbromarone and allopurinol in patients with stage 3 chronic kidney disease(CKD)complicated with hyperuricemia(HUA)and their effects on the function of renal tubules and glomerulus by retrospective analysis.Methods: The hospital information system(HIS)was used to screen and collect complete clinical data of patients with stage 3 CKD complicated with HUA,who met the following conditions:(1)They received diagnosis and treatment in the Department of Nephrology and Rheumatology of our hospital from 2016 to 2019,and had regular follow-up;(2)They met selection criteria and exclusion criteria;(3)They had been taking urate-lowering drugs for at least 12 months.A total of 121 cases were selected,including 60 cases taking febuxostat tablets,37 cases taking benzbromarone tablets,and 24 cases taking allopurinol tablets.Collect the data of laboratory indexes including serum uric acid(SUA),serum creatinine(Scr),blood urea nitrogen(BUN),urinary albumin/creatinine ratio(UACR),urinary retinol binding protein(RBP),urinary N-acetyl-?-D-Glucosaminidase(NAG),urinary ?2 microglobulin(?2-MG),urinary ?1 microglobulin(?1-MG),which were measured before and after 1 month,6months and 12 months of treatment.The e GFR was calculated by CKD-EPI equation.When SUA fell below 360?mol/L,it was regarded as reaching the standard.Calculate the proportion of patients with SUA<360?mol/L in each group.The international standard statistical software SPSS19.0 was used for data analysis.Results: Uric acid:(1)SUA: After treatment,the SUA level of each group was significantly lower than that before treatment(P<0.001).At 6 and 12 months of treatment,the SUA level of the febuxostat group was significantly lower than those of the other two groups(P<0.05),and there was no significant difference between benzbromarone group and allopurinol group at each time point(P>0.05).(2)Standard-reaching rate of serum uric acid: There was no statistical difference among three groups at 1 month of treatment(P>0.05).At 6 months of treatment,the standard-reaching rate of serum uric acid in the febuxostat group was significantly Vhigher than that of allopurinol group(P<0.05).At 12 months of treatment,the standard-reaching rate of serum uric acid in the febuxostat group was significantly higher than those of the other two groups(P<0.05).At each time point,there was no statistical difference between benzbromarone group and allopurinol group(P>0.05).The indicators of renal tubular function :(1)At 6 and 12 months of treatment,urinary NAG levels of the febuxostat group and allopurinol group decreased statistically compared with that before treatment(P<0.05).At 12 months of treatment,urinary NAG in the benzbromarone group decreased statistically compared with that before treatment(P<0.05).At other time points,there was no statistically significant decrease in urinary NAG level of each group compared with that before treatment(P>0.05).At 12 months of treatment,urinary RBP in the febuxostat group decreased statistically compared with that before treatment(P<0.05).At other time points,there was no statistically significant decrease in urinary RBP of the febuxostat group compared with that before treatment(P>0.05).The urinary RBP levels in the benzbromarone group and the allopurinol group had no significant changes after treatment(P>0.05).After treatment,the urinary ?1-MG levels and urinary ?2-MG levels in three groups had no significant changes(P>0.05).(2)Inter-group comparison: At 12 months of treatment,the urinary NAG in the febuxostat group was significantly lower than those in the other two groups(P<0.05),the urinary NAG in the benzbromarone group was similar to that in the allopurinol group(P>0.05).At the other time points,there was no statistical difference in the urinary NAG among three groups(P>0.05).There was no significant difference in urinary RBP,urinary ?1-MG or urinary ?2-MG among three groups at each time point(P>0.05).The indicators of glomerular function :(1)At 6 and 12 months of treatment,UACR levels and Scr levels in febuxostat group and allopurinol group decreased compared with that before treatment(P<0.05),and e GFR levels increased compared with that before treatment(P<0.05).At 12 months of treatment,Scr in benzbromarone group decreased compared with that before treatment(P<0.05),e GFR increased compared with that before treatment(P<0.05).After treatment,there was no statistically significant decrease in UACR of benzbromarone group compared with that before treatment(P>0.05).After treatment,the BUN levels of three groups had no significant changes(P>0.05).(2)Inter-group comparison: At 6 and 12 months of treatment,UACR of febuxostat group was significantly lower than that of benzbromarone group(P<0.05),there were no significant differences between febuxostat group and allopurinol group,and between benzbromarone group and allopurinol group(P>0.05).At 12 months of treatment,the Scr of febuxostat group was significantly lower than those of the other two groups,and the e GFR was significantly higher than those of the other two groups(P<0.05).There were no statistical differences in Scr and e GFR between benzbromarone group and allopurinol group.At the other time points,there were no statistical differences in Scr and e GFR among three groups(P>0.05).At each time point,there was no statistical difference in BUN among three groups(P>0.05).Multiple regression analysis showed that the age,the e GFR level before treatment,and the urinary NAG level before treatment were related to the e GFR level at 12 months of treatment.The e GFR level before treatment was positively related factor,Age and urinary NAG level before treatment were negatively related factors.Adverse reactions: The incidences of adverse reactions in the febuxostat group,benzbromarone group and allopurinol group were 6.7%,8.1% and 8.3%,respectively.There was no significant difference among three groups(P>0.05).Conclusion:(1)For patients in stage 3 CKD complicated with HUA,febuxostat,benzbromarone and allopurinol all have good efficacy in lowering uric acid,and febuxostat is superior to the other two.There was no significant difference in the incidence of adverse reactions.(2)All three can reduce injury of renal tubule and delay the decline of glomerular function,thereby delaying the progression of kidney disease.Febuxostat and allopurinol have the effect of reducing urinary albumin.With the prolonged treatment time,febuxostat is superior to benzbromarone and allopurinol in reducing injury of renal tubule and delaying decline of glomerular function.(3)For patients in stage 3 CKD complicated with HUA,taking febuxostat tablet for a long time to maintain uric acid at the standard level is more beneficial to renal protection. |
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