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JASN：Selonsertib对糖尿病肾病患者的影响

2019-09-11 xing.T MedSci原创

Selonsertib糖尿病肾病影响
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由此可见，虽然试验并未满足其主要终点，但探索性事后分析表明selonsertib可能减缓糖尿病肾病的进展。

由氧化应激引起的肾小球和肾小管细胞中凋亡信号调节激酶1（ASK1）活化可促进肾脏疾病进展。动物实验发现selonsertib（一种选择性ASK1抑制剂）可作为潜在的治疗药物。

近日，肾脏病领域权威杂志Journal of the American Society of Nephrology上发表一篇研究文章，在这项评估selonsertib在2型糖尿病患者和治疗难治性中晚期糖尿病肾病患者中的安全性和有效性的2期试验中，研究人员随机指定333名成人以1：1：1：1的比例分配接受selonsertib（口服每日剂量为2、6或18mg）或安慰剂治疗。该研究的主要结局是48周时基线eGFR的变化。

Selonsertib似乎是安全的，48周内没有剂量依赖性副作用。尽管selonsertib组和安慰剂组的平均eGFR在48周时没有显著差异，但selonsertib对肌酐分泌的抑制作用的急性效应混淆了48周时的eGFR差异。由于这种意想不到的效应，研究人员使用分段线性回归，发现两种剂量依赖性效应：高剂量的selonsertib组从0到4周发生急性和更明显的eGFR下降（肌酐分泌效应）以及4到48周之间减缓的eGFR下降（治疗效果）。事后分析（不包括来自两个具有良好临床实践依从性相关问题的患者数据）发现，相对于安慰剂组，selonsertib18mg组在4至48周之间，eGFR下降率降低了71％（差异为每年3.11±1.53毫升/分钟/1.73平方米; 95％置信区间为0.10-6.13；P=0.043）。selonsertib组和安慰剂组尿白蛋白与肌酐比率无显著差异。

由此可见，虽然试验并未满足其主要终点，但探索性事后分析表明selonsertib可能减缓糖尿病肾病的进展。 

原始出处

Glenn M. Chertow,et al.Effects of Selonsertib in Patients with Diabetic Kidney Disease.JASN,2019.https://jasn.asnjournals.org/content/early/2019/09/09/ASN.2018121231

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    2020-07-01 gostraight

    #肾病患者#

    0

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    2020-02-02 chenhongpeng

    #ASN#

    0

  3. [GetPortalCommentsPageByObjectIdResponse(id=2025871, encodeId=efef20258e188, content=<a href='/topic/show?id=a91d82583bf' target=_blank style='color:#2F92EE;'>#肾病患者#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=45, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=82583, encryptionId=a91d82583bf, topicName=肾病患者)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=db5b227, createdName=gostraight, createdTime=Wed Jul 01 11:03:00 CST 2020, time=2020-07-01, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1941374, encodeId=cdb119413e452, content=<a href='/topic/show?id=bd2f28e0e1' target=_blank style='color:#2F92EE;'>#ASN#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=36, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=2870, encryptionId=bd2f28e0e1, topicName=ASN)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=1777154, createdName=chenhongpeng, createdTime=Sun Feb 02 22:03:00 CST 2020, time=2020-02-02, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2007720, encodeId=4824200e7201a, content=<a href='/topic/show?id=806c16119b4' target=_blank style='color:#2F92EE;'>#Selonsertib#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=50, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=16119, encryptionId=806c16119b4, topicName=Selonsertib)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=568152, createdName=snowpeakxu, createdTime=Thu Sep 19 04:03:00 CST 2019, time=2019-09-19, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1042687, encodeId=7fb2104268ed1, content=谢谢MedSci提供最新的资讯, beContent=null, objectType=article, channel=null, level=null, likeNumber=52, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f0620, createdName=misszhang, createdTime=Thu Sep 12 00:03:00 CST 2019, time=2019-09-12, status=1, ipAttribution=)]
    2019-09-19 snowpeakxu

    #Selonsertib#

    0

  4. [GetPortalCommentsPageByObjectIdResponse(id=2025871, encodeId=efef20258e188, content=<a href='/topic/show?id=a91d82583bf' target=_blank style='color:#2F92EE;'>#肾病患者#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=45, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=82583, encryptionId=a91d82583bf, topicName=肾病患者)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=db5b227, createdName=gostraight, createdTime=Wed Jul 01 11:03:00 CST 2020, time=2020-07-01, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1941374, encodeId=cdb119413e452, content=<a href='/topic/show?id=bd2f28e0e1' target=_blank style='color:#2F92EE;'>#ASN#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=36, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=2870, encryptionId=bd2f28e0e1, topicName=ASN)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=1777154, createdName=chenhongpeng, createdTime=Sun Feb 02 22:03:00 CST 2020, time=2020-02-02, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2007720, encodeId=4824200e7201a, content=<a href='/topic/show?id=806c16119b4' target=_blank style='color:#2F92EE;'>#Selonsertib#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=50, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=16119, encryptionId=806c16119b4, topicName=Selonsertib)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=568152, createdName=snowpeakxu, createdTime=Thu Sep 19 04:03:00 CST 2019, time=2019-09-19, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1042687, encodeId=7fb2104268ed1, content=谢谢MedSci提供最新的资讯, beContent=null, objectType=article, channel=null, level=null, likeNumber=52, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f0620, createdName=misszhang, createdTime=Thu Sep 12 00:03:00 CST 2019, time=2019-09-12, status=1, ipAttribution=)]
    2019-09-12 misszhang

    谢谢MedSci提供最新的资讯

    0