Ghang Byeongzu, Park Jino, Lee Ji Sung, Lim Joon Seo, Kim Hyunwoo, Liew David F L, Kim Jinseok, Kang Duk-Hee, Yoo Bin
Division of Rheumatology, Department of Internal Medicine, Jeju National University School of Medicine, Jeju National University Hospital, Jeju, Korea.
Division of Cardiology, Department of Internal Medicine, Inje University Haeundae Paik Hospital, Inje University College of Medicine, Busan, Korea.
Kidney Int. 2025 Mar;107(3):521-529. doi: 10.1016/j.kint.2024.10.022. Epub 2024 Nov 16.
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.
基于高尿酸血症是慢性肾脏病（CKD）进展的一个可改变的危险因素这一假设，人们期望降尿酸治疗（ULT）能够延缓CKD的进展。在此，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）水平与肾功能的关联。为此，我们对在CARES试验中接受非布司他或别嘌醇ULT治疗超过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算肾小球滤过率（eGFR）斜率（eGFR的年变化率）。在5002例痛风患者中，3264例（65.3%）在中位随访2.5年期间接受ULT时eGFR升高。平均sUA水平升高与eGFR斜率下降显著相关（每升高1mg/dL，校正β为-0.1912）。倾向评分匹配分析表明，ULT期间平均sUA水平低于6mg/dL与eGFR下降风险降低显著相关（校正比值比：0.66，95%置信区间0.57-0.77）。尽管在一般人群中eGFR会随时间自然下降已得到充分证明，但参与CARES试验的患者中超过一半在接受ULT时并未出现eGFR下降。因此，我们的研究表明，通过ULT维持低sUA水平与痛风患者CKD进展风险降低显著相关。
