Department of Medicine, North Mississippi Medical Center, Tupelo.
Division of Nephrology, University of Tennessee Health Science Center, Memphis.
JAMA Netw Open. 2022 Jun 1;5(6):e2215878. doi: 10.1001/jamanetworkopen.2022.15878.
Uric acid is a waste metabolite produced from the breakdown of purines, and elevated serum uric acid levels are associated with higher risk of hypertension, cardiovascular disease, and mortality and progression of chronic kidney disease (CKD). Treatment of hyperuricemia in patients with preexisting CKD has not been shown to improve kidney outcomes, but the associations of uric acid-lowering therapies with the development of new-onset kidney disease in patients with estimated glomerular filtration rate (eGFR) within reference range and no albuminuria is unclear.
To examine the association of initiating uric acid-lowering therapy with the incidence of CKD.
DESIGN, SETTING, AND PARTICIPANTS: This cohort study included patients with eGFR of 60 mL/min/1.73 m2 or greater and no albuminuria treated at US Department of Veterans Affairs health care facilities from 2004 to 2019. Clinical trial emulation methods, including propensity score weighting, were used to minimize confounding. Data were analyzed from 2020 to 2022.
Newly started uric acid-lowering therapy.
The main outcomes were incidences of eGFR less than 60 mL/min/1.73 m2, new-onset albuminuria, and end-stage kidney disease.
A total of 269 651 patients were assessed (mean [SD] age, 57.4 [12.5] years; 252 171 [94%] men). Among these, 29 501 patients (10.9%) started uric acid-lowering therapy, and 240 150 patients (89.1%) did not. Baseline characteristics, including serum uric acid level, were similar among treated and untreated patients after propensity score weighting. In the overall cohort, uric acid-lowering therapy was associated with higher risk of both incident eGFR less than 60 mL/min/1.73 m2 (weighted subhazard ratio [SHR], 1.15 [95% CI, 1.10-1.20; P < .001) and incident albuminuria (SHR, 1.05 [95% CI, 1.01-1.09; P < .001) but was not associated with the risk of end-stage kidney disease (SHR, 0.96 [95% CI, 0.62-1.50]; P = .87). In subgroup analyses, the association of uric acid-lowering therapy with worse kidney outcomes was limited to patients with baseline serum uric acid levels of 8 mg/dL or less.
These findings suggest that in patients with kidney function within reference range, uric acid-lowering therapy was not associated with beneficial kidney outcomes and may be associated with potential harm in patients with less severely elevated serum uric acid levels.
尿酸是嘌呤分解产生的一种代谢废物，血清尿酸水平升高与高血压、心血管疾病以及慢性肾脏病（CKD）的风险增加、死亡率和进展相关。在患有 CKD 的患者中，治疗高尿酸血症并未显示出改善肾脏结局，但降低尿酸治疗与肾小球滤过率（eGFR）在参考范围内且无白蛋白尿的患者新发肾脏病的发展之间的关联尚不清楚。
研究启动降尿酸治疗与 CKD 发生率之间的关联。
设计、地点和参与者：这项队列研究纳入了 2004 年至 2019 年期间在美国退伍军人事务部医疗保健机构接受治疗、eGFR 为 60 mL/min/1.73 m2 或更高且无白蛋白尿的患者。采用临床试验模拟方法，包括倾向评分加权，以最大程度减少混杂因素。数据分析于 2020 年至 2022 年进行。
新开始的降尿酸治疗。
主要结局是 eGFR 低于 60 mL/min/1.73 m2、新发白蛋白尿和终末期肾病。
共评估了 269651 名患者（平均[SD]年龄 57.4[12.5]岁；252171[94%]为男性）。其中，29501 名患者（10.9%）开始降尿酸治疗，240150 名患者（89.1%）未接受治疗。经过倾向评分加权后，治疗组和未治疗组的基线特征，包括血清尿酸水平，相似。在总体队列中，降尿酸治疗与 eGFR 低于 60 mL/min/1.73 m2（加权亚危险比[SHR]，1.15[95%CI，1.10-1.20；P<0.001）和新发白蛋白尿（SHR，1.05[95%CI，1.01-1.09；P<0.001）的风险增加相关，但与终末期肾病的风险无关（SHR，0.96[95%CI，0.62-1.50]；P=0.87）。在亚组分析中，降尿酸治疗与肾脏结局恶化的关联仅限于基线血清尿酸水平为 8 mg/dL 或更低的患者。
这些发现表明，在肾功能处于参考范围内的患者中，降尿酸治疗与肾脏获益结局无关，并且可能与血清尿酸水平轻度升高的患者中潜在的危害相关。
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