译者：张文静 校对：马丹 审核：张莉芸

Abstract

BACKGROUND: The association between hyperuricemia, gout, and impaired renal function has long been recognized. Recent data provide evidence for the causal relationship between elevated serum urate (sUA) and renal changes, leading to declines in glomerular filtration rates. In healthy adults, glomerular filtration rate wanes with age. Urate-lowering therapy (ULT) with allopurinol has been shown to stabilize or reverse this.-IVE: Here we examine the long-term effects of ULT with febuxostat on estimated glomerular filtration rate (eGFR). METHODS: This is a post hoc analysis of the Febuxostat Open-label Clinical trial of Urate-lowering efficacy and Safety study, during which 116 hyperuricemic gout subjects received daily doses of febuxostat (40, 80, or 120 mg) for up to 5 years. sUA concentrations and eGFR were assessed regularly. Results were stratified by mean change in sUA from -line. Mathematical modeling was used to predict the effect of sUA reduction on eGFR.RESULTS: Maintenance or improvement in eGFR was inversely correlated with the quantitative reduction in sUA from -line. For every 1 mg/dL decrease in sUA, the model projected an expected improvement in eGFR of 1 mL/min from the untreated value.CONCLUSION: Individuals with the greatest reductions in sUA may experience reduced rates of renal deterioration or even stabilization of renal function. Further studies examining the impact of long-term ULT on renal function in hyperuricemic gout patients are needed to both confirm our results and verify if improvements in renal function are feasible in such patients.

摘要

背景：高尿酸血症，痛风，和肾功能受损之间的相关性早已被认可。最近研究证实了血尿酸升高和肾脏改变的因果关系，其可导致肾小球滤过率的下降。在健康成年人，肾小球滤过率随年龄而改变。已证实应用别嘌醇降尿酸治疗可稳定或逆转肾小球滤过率的下降。目的：本课题研究应用非布索坦降尿酸长期治疗对肾小球滤过率的影响。方法：本课题是一项关于非布索坦降尿酸治疗有效性安全性的开放性回顾性临床研究，共纳入116例高尿酸血症痛风患者，服用非布索坦治疗达(每日40mg, 80mg, 或120 mg) 共5年。规律监测血尿酸水平和肾小球滤过率，分析血尿酸水平较基线水平的变化，应用数学模型预测血尿酸降低对肾小球滤过率的影响。 结果：肾小球滤过率的维持或改善与血尿酸水平下降程度呈负相关，血尿酸水平每下降1mg/dl，预示着肾小球滤过率改善1ml/min。结论：患者血尿酸水平显著下降可降低肾功能恶化的几率或是肾功能维持稳定。尚需进一步研究来证实高尿酸血症的痛风患者，长期降尿酸治疗对肾功能的影响，包括肾功能改善在这些患者中的可行性。

引自: Whelton A, Macdonald PA, Zhao L, Hunt B, Gunawardhana L.Renal function in gout: long-term treatment effects of febuxostat. J Clin Rheumatol. 2011 Jan;17(1):7-13.