Department of Nephrology, Cleveland Clinic Foundation, Cleveland, Ohio, USA.
Department of Medicine, Cleveland Clinic Foundation, Cleveland, Ohio, USA.
Am J Nephrol. 2017;46(4):315-322. doi: 10.1159/000481460. Epub 2017 Oct 13.
Hyperuricemia is associated with the progression of chronic kidney disease (CKD), but it is not known whether the relationship is causal. We examined the association of hyperuricemia and uric acid lowering therapy (UALT) with progression of CKD in patients with CKD 3 and 4 in the Cleveland Clinic CKD registry.
We included 1,676 patients with CKD stages 3 and 4 from Ohio, who had measured their uric acid (UA) levels a year prior to the recording of the second eGFR <60 mL/min/1.73 m2, and follow-up eGFR, between 2005 and 2009. Our primary composite outcome included a 50% drop in eGFR or progression to ESRD. Secondary outcomes included the rate of decline in eGFR, all-cause mortality, progression to ESRD, and a composite measure of progression to ESRD or death. We assessed the association between UA, UALT, and outcomes using Cox models and competing risks regression models.
In multivariable models, higher UA was associated with the composite endpoint, but it reached statistical significance only in the 4th quartile (≥8.9 mg/dL). Receipt of UALT was significantly associated with increased risk of the composite outcome. Neither UA nor UALT (considered a time-dependent covariate) was significantly associated with mortality. The inference was similar for UA as high vs. low, quartiles, or continuous. Similarly, neither high UA nor UALT were significantly associated with ESRD, the composite of ESRD and mortality, or eGFR decline.
Hyperuricemia is associated with increased risk of progression to ESRD in patients with CKD stages 3 and 4, but UALT does not ameliorate the risk, suggesting that the relationship is not causal.
高尿酸血症与慢性肾脏病（CKD）的进展有关，但尚不清楚这种关系是否具有因果关系。我们在克利夫兰诊所 CKD 登记处检查了 CKD 3 期和 4 期患者中高尿酸血症和尿酸降低治疗（UALT）与 CKD 进展的关系。
我们纳入了来自俄亥俄州的 1676 名 CKD 3 期和 4 期患者，这些患者在记录第二次 eGFR<60 mL/min/1.73 m2 之前的一年和 2005 年至 2009 年之间的随访 eGFR 中测量了尿酸（UA）水平。我们的主要复合结局包括 eGFR 下降 50%或进展为 ESRD。次要结局包括 eGFR 下降率、全因死亡率、进展为 ESRD 以及 ESRD 或死亡的复合指标。我们使用 Cox 模型和竞争风险回归模型评估 UA、UALT 和结局之间的关系。
在多变量模型中，较高的 UA 与复合终点相关，但仅在第 4 四分位数（≥8.9 mg/dL）中具有统计学意义。接受 UALT 治疗与复合结局的风险增加显著相关。UA 或 UALT（被视为时间依赖性协变量）均与死亡率无显著相关性。UA 作为高 vs. 低、四分位数或连续变量的推断也相似。同样，高 UA 或 UALT 均与 ESRD、ESRD 和死亡率的复合或 eGFR 下降无显著相关性。
高尿酸血症与 CKD 3 期和 4 期患者进展为 ESRD 的风险增加相关，但 UALT 并不能降低风险，表明这种关系不是因果关系。
