Nephrology Section, New York Harbor VA Medical Center, and Division of Nephrology, New York University Langone Medical Center, New York, New York;, †Global Medical Affairs, Takeda Pharmaceuticals International, Deerfield, Illinois;, ‡Clinical Science, and §Statistics, Takeda Global Research & Development Center, Inc., Deerfield, Illinois, ‖Experimental Medicine, Takeda California, San Diego, California.
Clin J Am Soc Nephrol. 2013 Nov;8(11):1960-7. doi: 10.2215/CJN.01760213. Epub 2013 Aug 8.
Higher urinary uric acid excretion is a suspected risk factor for calcium oxalate stone formation. Febuxostat, a xanthine oxidoreductase inhibitor, is effective in lowering serum urate concentration and urinary uric acid excretion in healthy volunteers and people with gout. This work studied whether febuxostat, compared with allopurinol and placebo, would reduce 24-hour urinary uric acid excretion and prevent stone growth or new stone formation.
DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: In this 6-month, double-blind, multicenter, randomized controlled trial, hyperuricosuric participants with a recent history of calcium stones and one or more radio-opaque calcium stone ≥ 3 mm (as seen by multidetector computed tomography) received daily febuxostat at 80 mg, allopurinol at 300 mg, or placebo. The primary end point was percent change from baseline to month 6 in 24-hour urinary uric acid. Secondary end points included percent change from baseline to month 6 in size of index stone and change from baseline in the mean number of stones and 24-hour creatinine clearance.
Of 99 enrolled participants, 86 participants completed the study. Febuxostat led to significantly greater reduction in 24-hour urinary uric acid (-58.6%) than either allopurinol (-36.4%; P=0.003) or placebo (-12.7%; P<0.001). Percent change from baseline in the size of the largest calcium stone was not different with febuxostat compared with allopurinol or placebo. There was no change in stone size, stone number, or renal function. No new safety concerns were noted for either drug.
Febuxostat (80 mg) lowered 24-hour urinary uric acid significantly more than allopurinol (300 mg) in stone formers with higher urinary uric acid excretion after 6 months of treatment. There was no change in stone size or number over the 6-month period.
尿液中尿酸排泄量增加被认为是草酸钙结石形成的一个危险因素。黄嘌呤氧化酶抑制剂非布司他可有效降低健康志愿者和痛风患者的血清尿酸浓度和尿液尿酸排泄量。本研究旨在比较非布司他、别嘌醇和安慰剂在降低 24 小时尿尿酸排泄量和预防结石生长或新结石形成方面的效果。
设计、地点、参与者和测量方法：在这项为期 6 个月的、双盲、多中心、随机对照试验中，有近期钙结石病史且有一个或多个直径≥3mm（多排螺旋 CT 可见）的不透射线钙结石的高尿酸尿症参与者，每天接受非布司他 80mg、别嘌醇 300mg 或安慰剂治疗。主要终点是 6 个月时与基线相比 24 小时尿尿酸的变化百分比。次要终点包括与基线相比，6 个月时指数结石大小的变化百分比，以及基线时结石数量和 24 小时肌酐清除率的变化。
在 99 名入组的参与者中，有 86 名完成了研究。与别嘌醇（-36.4%；P=0.003）或安慰剂（-12.7%；P<0.001）相比，非布司他可显著降低 24 小时尿尿酸（-58.6%）。与别嘌醇或安慰剂相比，非布司他对最大钙结石大小的变化百分比无差异。结石大小、数量或肾功能均无变化。两种药物均未出现新的安全性问题。
在 6 个月的治疗后，与别嘌醇（300mg）相比，高尿酸尿症结石形成者中，非布司他（80mg）可显著降低 24 小时尿尿酸排泄量。在 6 个月的研究期间，结石大小或数量无变化。
