目的

：肾功能损害是痛风的一个危险因素，同时肾功能损害也是达到痛风最佳管理的一个障碍。我们开展本探索性研究旨在获取迄今为止非常有限的有关非布司他治疗中重度肾功能损害(GFR15-50ml/分/体表面积)痛风患者的疗效方面的资料。

方法

：96例合并中重度肾功能损害的痛风患者被纳入本项预期12个月的多中心、随机、双盲、安慰剂对照研究。这些患者按照1:1:1的比例接受30mg非布司他每天2次、40/80mg非布司他每天1次或安慰剂。主要的疗效终点是基线至12个月时血清肌酐水平的变化。次要终点包括基线至12个月时估算肾小球滤过率(GFR)的变化和12个月时血清尿酸水平低于6.0 mg/dl的患者比例。

结果

：治疗12个月时，非布司他治疗组与安慰剂治疗组相比，在血清肌酐变化、估算GFR变化上没有显著的差异。治疗12个月后两组非布司他治疗组患者达到血清尿酸水平低于6mg/dl的患者比例显著升高于安慰剂组。发生一次治疗突发性不良反应事件的几率在接受30mg非布司他每天2次治疗组、40/80mg非布司他每天1次治疗组和安慰剂组分别为78.1%、87.5%和78.1%。治疗突发性不良反应事件的发生绝大多数情况下与肾功能衰竭和损害以及肾功能分析的类别有关。

结论

：非布司他被证实可显著降低血尿酸，且对于中重度肾功能损害的痛风患者耐受性良好。随机接受非布司他治疗的患者，血尿酸水平显著降低，与此同时没有发现肾功能明显的恶化。

附原文Abstract OBJECTIVE:Renal impairment is a risk factor for gout and abarrier to optimal gout management. We undertook this exploratory study toobtain data that have been heretofore limited regarding the safety and efficacyof febuxostat in patients with moderate-to-severe renal impairment (estimatedglomerular filtration rate [GFR] 15-50 ml/minute/1.73 m(2) ).METHODS: Ninety-six gout patients withmoderate-to-severe renal impairment were enrolled in a 12-month multicenter,randomized, double-blind, placebo-controlled study. Patients were randomlyassigned at a 1:1:1 ratio to receive 30 mg febuxostat twice daily, 40/80 mgfebuxostat once daily, or placebo. The primary efficacy end point was thechange in serum creatinine (Cr) level from baseline to month 12. Secondary endpoints included the change in estimated GFR from baseline to month 12 and theproportion of patients with a serum uric acid (UA) level of <6.0 mg/dl atmonth 12.RESULTS: At month 12,there were no significant differences in the change in serum Cr level frombaseline, or in the change in estimated GFR from baseline, in either febuxostatgroup compared to the placebo group. The proportion of patients with a serum UAlevel of <6.0 mg/dl at month 12 was significantly greater in both febuxostatgroups compared to the placebo group (both P<0.001). At least 1treatment-emergentadverse event(TEAE) occurred in 78.1% of patients receiving 30 mgfebuxostat twice daily, 87.5% of patients receiving 40/80 mg febuxostat oncedaily, and 78.1% of patients receiving placebo. TEAEs most frequently involvedthe categories of renal failure and impairment and renal function analyses.CONCLUSION: Febuxostat proved to beefficacious inserum UA reduction and was well tolerated in gout patients with moderate-to-severe renal impairment. Patients randomly assigned to receive febuxostat demonstrated significantly lower serum UA levels and no significant deterioration in renal function.

引自：Saag KG,Whelton A,Becker MA,MacDonald P,Hunt B,Gunawardhana L.Impact of Febuxostat on Renal Function in Gout Patients With Moderate-to-Severe Renal Impairment.Arthritis Rheumatol.2016 Aug;68(8):2035-43. doi: 10.1002/art.39654.