何玉茂 徐良贤

摘 要 目的：观察非布司他治疗慢性肾脏病伴高尿酸血症的临床疗效和安全性。方法：选取72例慢性肾脏病伴高尿酸血症患者随机分为观察组和对照组各36例，观察组给予非布司他治疗，对照组维持之前治疗方案。随访24周，每4周查血常规、肝肾功能、血尿酸。结果：观察组自12周起血尿酸出现明显下降，显著低于基线水平，到第24周时血尿酸下降更为明显。对照组血尿酸水平至第20周起才出明显低于基线水平。至第16周～第24周时，观察组血尿酸水平明显低于对照组（P<0.05）。至第24周时，两组肾小球滤过率均分别低于基线水平，且观察组较对照组降低更为显著（P<0.05）。结论：非布司他可显著性降低慢性肾脏病伴高尿酸血症患者的血尿酸水平，减缓肾小球滤过率降低程度，疗效及安全性优于别嘌醇。

关键词 慢性肾脏病 高尿酸血症 降尿酸治疗 非布司他

中图分类号：R971.1； R589.7 文献标志码：B 文章编号：1006-1533（2018）21-0024-02

Clinical effect of febuxostat on 36 cases of hyperuricemia with chronic kidney disease

HE Yumao1， XU Liangxian2（1. Department of Nephrology， Jiujiang Hospital of Chinese Traditional Medicine， Jiangxi Jiujiang 332000， China； 2. Basic Experimental Center in Medical Center of Jiujiang University， Jiangxi Jiujiang 332000， China）

ABSTRACT Objective： To investigate the clinical effects and safety of febuxostat on hyperuricemia patients with chronic kidney disease （CKD）. Methods： Seventy-two patients with CKD complicated with hyperuricemia were randomly divided into an observation group and a control group with 36 cases each. The observation group was treated with febuxostat while the control group maintained the previous treatment plan. Follow up was lasted for 24 weeks， blood routine， liver and kidney function and blood uric acid were checked every 4 weeks. Results： The level of serum uric acid was significantly decreased and lower than baseline at 12th weeks in the observation group， but only at 20th week in the control group， and significantly lower in the observation group than the control group during 16-24 week （P<0.05）. At the 24th week， the glomerular filtration rate in the two groups were lower than the baseline level and was significantly lower in the observation group than the control group （P<0.05）. Conclusion： Febuxostat can significantly reduce the level of serum uric acid in patients with CKD and hyperuricemia， and can slow down the decrease of glomerular filtration rate and its efficacy and safety are better than allopurinol.

KEy WORDS chronic kidney disease； hyperuricemia； uric acid reduction； febuxostat

人體中的尿酸主要依赖肾脏进行排泄，各种因素引起肾小球滤过率下降均有可能导致高尿酸血症（hyperuricemia），近些年来，研究揭示在慢性肾脏病（chronic kidney disease， CKD）的发生发展中，高尿酸血症发挥着非常重要的作用[1-3]，采用降尿酸药物治疗可显著延缓慢性肾脏病的发展进程。别嘌醇作为当前临床常用的降尿酸药物，抑制尿酸合成作用已被广泛认可，其作用机制是抑制黄嘌呤氧化酶（xanthine oxidase， XO）活性，从而抑制次黄嘌呤和黄嘌呤向尿酸转化的过程，减少尿酸的合成，降低血尿酸水平，但研究发现[4-6]，在其与XO的相互作用过程中，XO活性可因其钼活性中心自发性还原而恢复，从而降低别嘌醇的临床效果。除此之外，别嘌醇作为一种嘌呤类似物，还会影响到嘌呤与嘧啶代谢，因此其不良反应比较多。非布司他作为新型XO活性抑制剂，其作用不受氧化还原的影响，且不属于嘌呤类似物，各种不良反应相对较少，其在临床主要用于治疗有长期痛风症状的高尿酸血症病例，但在治疗慢性肾脏病伴高尿酸血症患者的报道还不多。……