Abstract: Background　Febuxostat is safe and effective for non-end-stage chronic kidney disease，which can reduce the serum uric acid and delay the progression of renal insufficiency.Diabetic nephropathy （DN）patients are more prone to hyperuricemia （HUA）．Objective　To investigate the urate-lowering efficacy and renal effect of febuxostat in non-end-stage DN with HUA.Methods　A prospective，randomized，controlled trial was conducted from February 2017 to February 2018 among non-end-stage DN with HUA inpatients and outpatients （n=140） treated in nephrology，endocrinology departments，or community health organizations of Henan Provincial People's Hospital.Participants were randomly assigned to either treatment group or control group，and received the same treatment，except that the former group received febuxostat（40 mg，once daily），while the latter received no pharmaceutical therapy for lowering uric acid.Serum uric acid （SUA），serum creatinine （Scr），albumin-to-creatinine ration （ACR） and other clinical parameters were measured at baseline and 1-6 months after treatment.The changes of SUA，ACR and estimated glomerular filtration rate （eGFR） were compared between the two groups.Results　Overall，112 cases completed the trial，including 58 in the treatment group and 54 in the control group.There were no significant differences in sex ratio，average age，body mass index （BMI），baseline blood pressure levels，SUA，Scr，ACR and eGFR between the two groups （P>0.05）．The analysis showed that the number and the rate of achieving target SUA level in the treatment group were 42 （77.8%），47 （87.0%），51 （94.4%），52 （96.3%），52 （96.3%），52 （96.3%），respectively，at the end of 1st，2nd，3rd，4th，5th，and 6th months of treatment.Compared with baseline，post-treatment eGFR level increased significantly in the treatment group 〔（56.42±14.49） ml?min-1?（1.73 m2）-1 vs （50.95±13.66）ml?min-1?（1.73 m2）-1〕.Treatment group showed much lower post-treatment HbA1c，TC，LDL-C，SUA，Scr and ACR levels compared with the control group （P<0.05）．Pearson correlation analysis showed that the duration of diabetes，SBP，HbA1c，and SUA were positively correlated with ACR，while eGFR was negatively correlated with ACR （P<0.05）；the duration of diabetes，HbA1c，LDL-C，SUA，SCr and ACR were negatively correlated with eGFR （P<0.05）．Stepwise multiple linear regression analysis showed that duration of diabetes，HbA1c and SUA were the influencing factors of ACR （P<0.05），and duration of diabetes，SUA and Scr were the independent influencing factors of eGFR （P<0.05）．Conclusion　For those also with HUA，this treatment could effectively reduce the SUA level，decrease the incidence of proteinuria，and delay the progression of renal insufficiency.

Key words: Diabetic nephropathies, Non end-stage, Hyperuricemia, Febuxostat, Renal function, Validation studies

摘要： 背景　非布司他可以安全有效地应用于非终末期慢性肾脏病患者中，降低血尿酸（SUA）及延缓肾功能不全的进展。糖尿病肾病（DN）并发高尿酸血症（HUA）的比例高于正常人群。目的　通过前瞻性随机对照临床研究评估非布司他治疗非终末期DN伴HUA患者的疗效及其对肾功能的影响。方法　选取2017年2月—2018年2月于河南省人民医院肾内科、内分泌科及社区住院或门诊诊治的DN伴HUA患者140例，按随机数字表法分为对照组和治疗组，对照组不使用降尿酸药物，治疗组给予非布司他40 mg/次，1次/d。收集患者基线及治疗1~6个月时的SUA、血肌酐（Scr）、尿微量蛋白与肌酐比值（ACR）等指标，比较两组患者SUA、ACR及估算肾小球滤过率（eGFR）的变化情况。结果　符合入选条件并完成试验的患者共112例，对照组和治疗组分别为58例和54例，两组患者年龄、性别、体质指数（BMI）及基线收缩压、SUA、Scr、ACR、eGFR比较，差异无统计学意义（P>0.05）。疗效分析显示，治疗组在治疗1~6个月时SUA达标人数（达标率）分别为42例（77.8%）、47例（87.0%）、51例（94.4%）、52例（96.3%）、52例（96.3%）、52例（96.3%）。治疗6个月后，非布司他治疗组eGFR高于基线水平〔（56.42±14.49）  ml?min-1?（1.73 m2）-1比（50.95±13.66） ml?min-1?（1.73 m2）-1〕，差异有统计学意义（P<0.05）；非布司他治疗组HbA1c、TC、LDL-C、SUA、Scr、ACR低于对照组，eGFR高于对照组，差异具有统计学意义（P<0.05）。Pearson相关分析结果显示，糖尿病病程、SBP、HbA1c、SUA与ACR呈线性正相关（P<0.05）；年龄、糖尿病病程、HbA1c、LDL-C、SUA、SCr、ACR均与eGFR呈线性负相关（P<0.05）。逐步多元线性回归结果显示，糖尿病病程、HbA1c、SUA是ACR的影响因素（P<0.05），而糖尿病病程、SUA、Scr是eGFR的影响因素（P<0.05）。结论　非布司他能有效降低非终末期DN伴HUA患者SUA水平，减少蛋白尿，延缓肾功能不全的进展。

关键词: 糖尿病肾病, 非终末期, 高尿酸血症, 非布司他, 肾功能, 有效性研究