Febuxostat provides renoprotection in patients with hyperuricemia or gout: a systematic review and meta-analysis of randomized controlled trials

It is unknown whether febuxostat can delay the progression of kidney dysfunction and reduce kidney endpoint events. The aim was to evaluate the renoprotective effect of febuxostat in patients with hyperuricemia or gout by performing a meta-analysis of randomized controlled trials (RCTs).
MEDLINE, Web of science, EMBASE, ClinicalTrials.gov, and the Cochrane Central Register for Randomized Controlled Trials were searched. The main outcomes included kidney events (serum creatinine doubling or progression to end-stage kidney disease or dialysis). The secondary outcomes were the rate of change in the estimated glomerular filtration rate (eGFR) and changes in the urine protein or urine albumin to creatinine ratio from baseline to the end of follow-up. We used random-effects models to calculate the pooled risk estimates and 95% CIs.
A total of 16 RCTs were included in the meta-analysis. In comparison with the control group, the patients who received febuxostat showed a reduced risk of kidney events (RR = 0.56, 95% CI 0.37–0.84, p = 0.006) and a slower decline in eGFR (WMD = 0.90 mL/min/1.73 m2, 95% CI 0.31–1.48, p = 0.003). The pooled results also revealed that febuxostat use reduced the urine albumin to creatinine ratio (SMD = −0.21, 95% CI −0.41 to −0.01, p = 0.042).
Febuxostat use is associated with a reduced risk of kidney events and a slow decline in eGFR. In addition, the urine albumin to creatinine ratio decreased in febuxostat users. Accordingly, it is an effective drug for delaying the progression of kidney function deterioration in patients with gout.
Systematic review registration: PROSPERO CRD42021272591

目前尚不明确非布司他是否可延缓肾功能不全进展并降低肾脏终点事件的发生风险。本研究旨在通过对随机对照试验（randomized controlled trials, RCTs）开展荟萃分析，评估非布司他对高尿酸血症或痛风患者的肾脏保护作用。
我们检索了MEDLINE、Web of Science、EMBASE、ClinicalTrials.gov以及Cochrane随机对照试验中心注册库。主要结局指标包括肾脏事件（血清肌酐翻倍进展至终末期肾病或需行透析治疗）；次要结局指标包括估算肾小球滤过率（estimated glomerular filtration rate, eGFR）的变化速率，以及从基线至随访结束时尿蛋白或尿白蛋白肌酐比值的变化。本研究采用随机效应模型计算合并风险估计值与95%置信区间（95% CIs）。
本荟萃分析共纳入16项RCTs。与对照组相比，接受非布司他治疗的患者肾脏事件发生风险显著降低（相对风险RR=0.56，95%CI 0.37–0.84，p=0.006），eGFR下降速率显著减缓（加权均数差WMD=0.90 mL/min/1.73 m²，95%CI 0.31–1.48，p=0.003）。合并分析结果同时显示，使用非布司他可降低尿白蛋白肌酐比值（标准化均数差SMD=-0.21，95%CI -0.41~-0.01，p=0.042）。
使用非布司他与肾脏事件发生风险降低及eGFR下降速率减缓存在相关性。此外，非布司他使用者的尿白蛋白肌酐比值有所下降。据此可见，非布司他是延缓痛风患者肾功能恶化进展的有效药物。
系统评价注册信息：PROSPERO CRD42021272591