低剂量非布司他在合并高尿酸血症的慢性肾脏病患者中,与别嘌醇相比具有更好的肾脏保护作用和非劣效性的安全性:一项双中心、随机、对照研究。

Low-dose febuxostat exhibits a superior renal-protective effect and non-inferior safety profile compared to allopurinol in chronic kidney disease patients complicated with hyperuricemia: A double-centre, randomized, controlled study.

作者信息

Yang Na, Cao Bin

机构信息

Department of Nephrology, Shangluo Central Hospital, Shangluo, China.

Department of Nephrology, Ankang Hospital of Traditional Chinese Medicine, Ankang, China.

出版信息

J Clin Pharm Ther. 2022 Dec;47(12):2214-2222. doi: 10.1111/jcpt.13794. Epub 2022 Nov 20.

Abstract

WHAT IS KNOWN AND OBJECTIVE

The present study compared the efficacy and safety of low-dose febuxostat versus allopurinol in chronic kidney disease (CKD) patients complicated with hyperuricemia (HUA).

METHODS

In this double-centre, randomized, controlled study, 120 CKD patients complicated with HUA were recruited and randomly assigned to low-dose febuxostat group (20 mg/day) or allopurinol group (200 mg/day) at 1:1 ratio. The serum creatinine (Scr), serum uric acid (SUA), and estimated glomerular filtration rate (eGFR) were measured at baseline (M0), month (M) 1, M3, and M6. Besides, the drug-related adverse events (AEs) were recorded. The primary outcome was the proportion of patients showing a > 10% decline in eGFR from M0 to M6.

RESULTS

The eGFR level was increased at M6, but similar at M0, M1 and M3 in febuxostat group compared with allopurinol group. Notably, the proportion of patients with >10% decline in eGFR from M0 to M6 was decreased in febuxostat group compared with allopurinol group. However, there was no difference of Scr, SUA at M0, M1, M3 and M6 between febuxostat group and allopurinol group. Moreover, there was no difference of drug-related AEs between febuxostat group and allopurinol group. Further subgroup analysis exhibited that low-dose febuxostat presented superior effect on attenuating eGFR decline and lowering SUA level compared with allopurinol in CKD stage 3 subgroup, but not in CKD stage 2 subgroup.

CONCLUSION

Low-dose febuxostat may exhibit a superior renal-protective effect, non-inferior SUA lowering ability and safety profile compared with allopurinol in CKD patients complicated with HUA.

摘要

已知信息与研究目的

本研究比较了低剂量非布司他与别嘌醇在慢性肾脏病(CKD)合并高尿酸血症(HUA)患者中的疗效和安全性。

方法

在这项双中心、随机、对照研究中,招募了120例CKD合并HUA患者,并按1:1比例随机分为低剂量非布司他组(20毫克/天)或别嘌醇组(200毫克/天)。在基线(M0)、第1个月(M1)、第3个月(M3)和第6个月(M6)测量血清肌酐(Scr)、血清尿酸(SUA)和估算肾小球滤过率(eGFR)。此外,记录药物相关不良事件(AE)。主要结局是从M0到M6时eGFR下降超过10%的患者比例。

结果

与别嘌醇组相比,非布司他组在M6时eGFR水平升高,但在M0、M1和M3时相似。值得注意的是,与别嘌醇组相比,非布司他组从M0到M6时eGFR下降超过10%的患者比例降低。然而,非布司他组和别嘌醇组在M0、M1、M3和M6时的Scr、SUA没有差异。此外,非布司他组和别嘌醇组在药物相关AE方面没有差异。进一步的亚组分析显示,在CKD 3期亚组中,低剂量非布司他在减轻eGFR下降和降低SUA水平方面比别嘌醇表现出更好的效果,但在CKD 2期亚组中并非如此。

结论

在CKD合并HUA患者中,低剂量非布司他与别嘌醇相比,可能具有更好的肾脏保护作用、不逊色的降低SUA能力和安全性。

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