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Lancet Diabetes Endo:达格列净对有无2型糖尿病的慢性肾病患者尿蛋白量的影响

2021-10-05 Nebula MedSci原创

无论有无合并2型糖尿病,达格列净均可显著减少慢性肾病患者的蛋白尿,而且在合并2型糖尿病的患者中的相对减少幅度更大

慢性肾病患者蛋白尿的减少与随后发生肾功能衰竭的风险降低有关。SGLT2抑制剂达格列净可显著减少肾功能正常或接近正常的2型糖尿病患者的蛋白尿。但达格列净在合并或不合并2型糖尿病的慢性肾病患者中是否还具有此效果尚不清楚。

DAPA-CKD研究是一项在21个国家的386个地点开展的多中心、双盲、安慰剂为对照的随机试验,评估了达格列净对有无合并2型糖尿病的慢性肾病患者蛋白尿的影响。

招募了确诊的慢性肾病患者(eGFR=25-75 mL/min·1.73 m2, 尿白蛋白肌酐比值(UACR)=200~5000 mg/g[22.6~565.6 mg/mmol]),随机分成达格列净组(达格列净 10 mg/日)或安慰剂组。预定的探索性终点是蛋白尿的变化。

2017年2月2日至2020年4月3日期间,共招募了4304位患者被随机分至达格列净组(n=2152)或安慰剂组(n=2152)。中位UACR为 949 mg/g (范围 477~1885)。总体上,与安慰剂相比,达格列净可使患者的几何平均UACR减少了29.3%(95% CI -33.1~-25.2; p<0.0001);达格列净组合并2型糖尿病的和不合并2型糖尿病的患者的几何平均UACR分布降低了35.1% (95% CI -39.4~30.6; p<0.0001) 和14·8% (-22.9~-5.9; p=0.0016)。

与安慰剂相比,达格列净对几何平均UACR的影响

在基线UACR≥300 mg/g的3860位患者中,达格列净提高了UACR分期降期(从大量蛋白尿变成了微量蛋白尿或无蛋白尿)的可能性(风险比[HR] 1.81, 95% CI 1.60~2.05)。在基线UACR<300 mg/g的3820位患者中,达格列净降低了UACR分期进展的风险(HR 0.41, 0.32~0.52)。在达格列净治疗期间第14天UACR的较大幅度降低与后续随访期间eGFR下降减慢显著相关(每单位UACR变化的β -3.06, 95% CI -5.20~-0.90; p=0.0056)。

综上所述,在无论有无合并2型糖尿病的慢性肾病患者中,达格列净依然可显著减少蛋白尿,而且在合并2型糖尿病的患者中的相对减少幅度更大。达格列净对有或无合并2型糖尿病的患者的临床预后的影响效果相近,但对UACR的作用不同,提示达格列净在慢性肾病患者中的这种保护作用部分可能是通过与蛋白尿减少无关的信号通路发挥的。

原始出处:

Niels Jongs, et al. Effect of dapagliflozin on urinary albumin excretion in patients with chronic kidney disease with and without type 2 diabetes: a prespecified analysis from the DAPA-CKD trial. The Lancet Diabetes & Endocrinology. October 04, 2021. https://doi.org/10.1016/S2213-8587(21)00243-6

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    2021-11-06 howi
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beContent=null, objectType=article, channel=null, level=null, likeNumber=103, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20210804/5785b262ac614e2787c8b09e8d8ae840/5cf1162cd10d42bc817ae4b32662d7f8.jpg, createdBy=c27d4938136, createdName=小小的丁香花, createdTime=Wed Oct 06 07:26:10 CST 2021, time=2021-10-06, status=1, ipAttribution=)]
    2021-10-07 老龙一点

    学习

    0

  8. 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  9. 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    2021-10-06 乔小霞

    不错的文章

    0

  10. 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    2021-10-06 小小的丁香花

    好文,提供了新的研究思路。

    0

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