Based on the hypothesis that hyperuricemia is a modifiable risk factor for chronic kidney disease (CKD) progression, there is an expectation that urate-lowering therapy (ULT) could delay the progression of CKD. Here, we investigated changes in kidney function and the association of the serum uric acid (sUA) level and kidney function during ULT in patients with gout. To do this we conducted post-hoc analysis on patients who received ULT with either febuxostat or allopurinol for more than six months in the CARES trial. The estimated glomerular filtration rate (eGFR) slope (annual rate of change in eGFR) was calculated using the CKD-EPI creatinine equation and linear mixed modeling. Among the 5,002 patients with gout, 3,264 (65.3%) demonstrated an increased eGFR while receiving ULT over a median follow-up of 2.5 years. Increased average sUA levels were significantly associated with declines in eGFR slope (per 1 mg/dL increase, (adjusted beta of -0.1912). Propensity score matched analysis demonstrated a significant association between low average sUA levels below 6 mg/dL during ULT and a reduced risk of eGFR decline (adjusted odds ratio: 0.66, 95% confidence interval 0.57–0.77). Despite the well-documented natural decline of eGFR over time in the general population, more than half of the patients enrolled in the CARES trial did not experience declines in eGFR while receiving ULT. Thus, our study shows maintaining low sUA levels with ULT was significantly associated with a decreased risk of CKD progression in patients with gout.

中文翻译：

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CARES 试验的事后分析表明，痛风患者在降尿酸治疗期间慢性肾病进展延迟


基于高尿酸血症是慢性肾脏病 （CKD） 进展的可改变危险因素的假设，预计降尿酸疗法 （ULT） 可以延缓 CKD 的进展。在这里，我们研究了痛风患者在 ULT 期间肾功能的变化以及血清尿酸 （sUA） 水平与肾功能的关系。为此，我们在 CARES 试验中对接受非布司他或别嘌呤醇 ULT 超过 6 个月的患者进行了事后分析。使用 CKD-EPI 肌酐方程和线性混合模型计算估计的肾小球滤过率 （eGFR） 斜率（eGFR 的年变化率）。在 5,002 名痛风患者中，3,264 名 （65.3%） 在中位随访 2.5 年期间接受 ULT 时表现出 eGFR 升高。平均 sUA 水平升高与 eGFR 斜率下降显著相关（每增加 1 mg/dL，（调整后的 beta 为 -0.1912）。倾向评分匹配分析表明，ULT 期间低于 6 mg/dL 的低平均 sUA 水平与 eGFR 下降风险降低之间存在显著相关性（调整比值比：0.66,95% 置信区间 0.57-0.77）。尽管有充分证据表明普通人群的 eGFR 随着时间的推移自然下降，但超过 60 岁的 CARES 试验入组患者在接受 ULT 时没有出现 eGFR 下降。因此，我们的研究表明，使用 ULT 维持低 sUA 水平与痛风患者 CKD 进展风险降低显着相关。