孙晶教授专访丨畅谈肾内科学科建设，解读罗沙司他最新研究

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关键词：新研究内科谈专访

资讯来源：中国医学论坛报

发布时间： 2022-09-30

肾性贫血是终末期肾病患者最常见的并发症之一，严重影响患者的预后。肾性贫血很大程度上是由于肾红细胞生成素(EPO)的产生不足和红细胞（RBC）生成减少所致，在肾功能衰竭患者中可观察到RBC存活率的显著下降。既往研究显示¹，红细胞生成刺激剂（ESA）可以延长RBC寿命。罗沙司他作为新型HIF-PHI类药物在CKD的治疗中取得了良好疗效，相比于ESA，罗沙司他是否可以更显著延长RBC寿命，有待进一步探明。

山东省立医院王荣教授、孙晶教授团队在系统性疾病肾损害、肾小球疾病诊治等领域深耕多年，成果颇丰。团队于2021年发表的研究显示，罗沙司他比重组人促红细胞生成素（rHu-EPO）具有更显著的延长红细胞存活率的效果。目前，王荣、孙晶教授团队针对该研究方向亦有诸多新的研究规划。

在此背景下，本文特邀孙晶教授，为我们解读罗沙司他相关研究成果及未来研究规划，并就肾内科学科建设等话题发表精彩看法。

</section><p data-brushtype="text" style="text-align:center;">视频名称</p></section></section></section><section data-role="paragraph" style="font-size: 15px;letter-spacing: 2px;font-family: 微软雅黑;"><section><section style="margin-bottom:-13px;text-align:center;"><iframe allowfullscreen="true" class="video_iframe rich_pages" data-ratio="1.7777777777777777" data-src="https://v.qq.com/iframe/preview.html?width=500&height=375&auto=0&vid=w3358iki7kx" data-vidtype="1" data-w="864" frameborder="0" scrolling="no" style="border-radius: 4px;"/></section><p data-brushtype="text" style="text-align:center;"><strong><span style="color: #7f7f7f;font-size: 12px;">孙晶教授专访</span></strong></p></section><p style="text-align:center;max-inline-size: 100%;margin: 0px 0px 5px;padding: 0px;clear: both;min-height: 1em;cursor: text;color: rgb(54, 96, 146);font-size: 16px;letter-spacing: 1.5px;caret-color: rgb(255, 0, 0);line-height: normal;box-sizing: border-box !important;overflow-wrap: break-word !important;outline: currentcolor none 0px !important;font-family: 微软雅黑;"><br/></p></section><section style="font-family: 微软雅黑;"><section data-color="#fac08f" data-id="116447" data-role="title" data-tools="135编辑器"><section style="margin: 20px auto;"><section style="display: flex;justify-content: center;"><section><section style="display: flex;justify-content: center;"><section style="transform-style: preserve-3d;"><section style="display: flex;justify-content: flex-start;transform: translateZ(5px);transform: translateZ(5px);-webkit-transform: translateZ(5px);-moz-transform: translateZ(5px);-ms-transform: translateZ(5px);-o-transform: translateZ(5px);"><section style="box-sizing:border-box;width: 30px;height: 30px;border-radius: 100%;background-color: #fff5f5;flex-shrink: 0;overflow: hidden;"><br/></section></section><section style="padding-left: 10px;margin-top: -18px;transform: translateZ(10px);transform: translateZ(10px);-webkit-transform: translateZ(10px);-moz-transform: translateZ(10px);-ms-transform: translateZ(10px);-o-transform: translateZ(10px);"><p style="text-align:center;background-color: #f9f8f0;border-left: 4px solid #fac08f;border-right: 4px solid #fac08f;color: #f6892d;font-size: 16px;padding: 5px 10px;letter-spacing: 1.5px;line-height: 1.75em;"><strong data-brushtype="text" style="caret-color: red;">相较于重组人促红细胞生成素，</strong></p><p style="text-align:center;background-color: #f9f8f0;border-left: 4px solid #fac08f;border-right: 4px solid #fac08f;color: #f6892d;font-size: 16px;padding: 5px 10px;letter-spacing: 1.5px;line-height: 1.75em;"><strong data-brushtype="text" style="caret-color: red;">罗沙司他可更显著延长血透患者红细胞寿命</strong><br/></p></section></section></section></section></section></section></section><section data-role="paragraph"><p><br/></p></section></section><section data-role="paragraph" style="font-family: 微软雅黑;"><p style="line-height: 2em;"><span style="text-align: justify;caret-color: red;text-indent: 0em;letter-spacing: 2px;color: #000000;">王荣、孙晶教授2021年发表的该项研究，旨在比较接受罗沙司他或重组人促红细胞生成素（rHu-EPO）治疗的血透患者与健康人的红细胞寿命。该项研究共纳入102例长期接受血液透析的CKD患者，其中62例接受rHu-EPO治疗，40例接受罗沙司他治疗，另招募25例健康受试者为对照组。研究采用肺泡CO浓度来估计红细胞寿命：先收集受试者透析之前呼出的气体1000mL，后以ELS测试仪和Levitt公式来检测和计算气体中CO浓度。</span></p><p style="line-height: 2em;"><br/></p><p style="line-height: 2em;"><span style="letter-spacing: 2px;text-align: justify;text-indent: 0em;caret-color: red;">研究结果显示，在单变量分析中，</span><strong><span style="letter-spacing: 2px;text-align: justify;text-indent: 0em;caret-color: red;">血红蛋白水平(图1)和磷酸盐水平(图2)与RBC存活时间正相关</span></strong><span style="letter-spacing: 2px;text-align: justify;text-indent: 0em;caret-color: red;">，具有统计学意义(p <0.05)。</span></p><p style="line-height: 2em;"><br/></p><p style="text-align:center;"><span style="letter-spacing: 2px;text-align: justify;text-indent: 0em;caret-color: red;"><img data-ratio="0.5862068965517241" src="https://zfz-oss.oss-cn-hangzhou.aliyuncs.com/temp/dc4fe15bf4dbf90b759312ab367736d9.png" data-w="725" style="max-width: 100% !important;box-sizing:border-box;vertical-align: inherit;width: 100%;"/></span></p><p style="text-align:center;margin-top: 0px;margin-bottom: 0px;"><span microsoft="" style="color: rgb(127, 127, 127);font-size: 14px;font-family: 微软雅黑, " yahei="">图1 血红蛋白水平与RBC寿命的关系</span></p><p style="text-align:center;margin-top: 0px;margin-bottom: 0px;"><br/></p><p style="text-align:center;margin-top: 0px;margin-bottom: 0px;"><span microsoft="" style="color: rgb(127, 127, 127);font-size: 14px;font-family: 微软雅黑, " yahei=""><img data-ratio="0.5875862068965517" src="https://zfz-oss.oss-cn-hangzhou.aliyuncs.com/temp/8020ed019368be4828b9ab88707299d5.png" data-w="725" style="max-width: 100% !important;box-sizing:border-box;vertical-align: inherit;width: 100%;"/></span></p><p style="text-align:center;"><span microsoft="" style="color: rgb(127, 127, 127);font-size: 14px;font-family: 微软雅黑, " yahei="">图2 磷酸盐水平与RBC寿命的关系</span></p><p style="text-align:center;"><br/></p><p style="text-align:justify;text-indent: 0em;line-height: 2em;"><span microsoft="" style="font-size: 15px;letter-spacing: 2px;font-family: 微软雅黑, " yahei=""><span microsoft="" style="font-size: 15px;line-height: 150%;letter-spacing: 2px;font-family: 微软雅黑, " yahei="">rHu-EPO、罗沙司他和对照组的中位RBC存活时间分别为65.0天、75.5天和108.0天。与健康受试者相比，血透患者的RBC存活时间存在显著差异(p <0.001)。</span><strong><span microsoft="" style="font-size: 15px;line-height: 150%;letter-spacing: 2px;font-family: 微软雅黑, " yahei=""><strong>罗沙司他组的中位</strong><strong>RBC寿命比rHu-EPO组高16.2%，接受罗沙司他治疗的患者的RBC存活时间明显长于接受rHu-EPO治疗的患者</strong></span></strong><span microsoft="" style="font-size: 15px;line-height: 150%;letter-spacing: 2px;font-family: 微软雅黑, " yahei="">(p <0.05，图3）。</span></span></p><p style="text-align:justify;text-indent: 0em;line-height: 2em;"><br/></p><p style="text-align:center;text-indent: 0em;line-height: 2em;"><span microsoft="" style="font-size: 15px;line-height: 150%;letter-spacing: 2px;font-family: 微软雅黑, " yahei=""><img data-ratio="0.9701726844583988" src="https://zfz-oss.oss-cn-hangzhou.aliyuncs.com/temp/0b653803ea04e787dd80e17d75d4c1d8.png" data-w="637" style="max-width: 100% !important;box-sizing:border-box;vertical-align: inherit;width: 100%;"/></span></p><p style="text-align:center;"><span microsoft="" style="font-size: 14px;color: rgb(127, 127, 127);font-family: 微软雅黑, " yahei="">图3 接受rHu-EPO或罗沙司他治疗的血透患者和对照组的RBC存活天数</span></p><p style="text-align:center;"><br/></p><p style="text-align:justify;line-height: 2em;text-indent: 0em;"><span microsoft="" style="font-size: 15px;letter-spacing: 2px;font-family: 微软雅黑, " yahei=""><span microsoft="" style="font-size: 15px;line-height: 150%;font-weight: normal;letter-spacing: 2px;font-family: 微软雅黑, " yahei="">该研究证实，对于接受血透的肾衰竭患者来说，贫血治疗药物（rHu-EPO或</span><span microsoft="" style="font-size: 15px;line-height: 150%;letter-spacing: 2px;font-family: 微软雅黑, " yahei="">罗沙司他）、血红蛋白水平和磷酸盐水平都会影响RBC存活时间。药物选择上，罗沙司他更有助于延长血透患者的红细胞寿命。</span></span></p></section><section data-role="paragraph" 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15px;letter-spacing: 2px;box-sizing: border-box !important;overflow-wrap: break-word !important;outline: currentcolor none 0px !important;font-family: 微软雅黑;"><p style="text-align:center;max-inline-size: 100%;margin: 0px 0px 5px;padding: 0px;clear: both;min-height: 1em;cursor: text;color: rgb(54, 96, 146);font-size: 16px;letter-spacing: 1.5px;caret-color: rgb(255, 0, 0);line-height: normal;box-sizing: border-box !important;overflow-wrap: break-word !important;outline: currentcolor none 0px !important;font-family: 微软雅黑;"><strong style="max-inline-size: 100%;margin: 0px;padding: 0px;box-sizing: border-box !important;overflow-wrap: break-word !important;outline: none 0px !important;cursor: text;"><span style="max-inline-size: 100%;margin: 0px;padding: 0px;box-sizing: border-box !important;overflow-wrap: break-word !important;outline: none 0px !important;cursor: text;color: #000000;font-size: 15px;text-shadow: none;letter-spacing: 2px;"><strong style="max-inline-size: 100%;margin: 0px;padding: 0px;box-sizing: border-box !important;overflow-wrap: break-word !important;outline: none 0px !important;cursor: text;">孙晶教授</strong></span></strong></p><p style="text-align:center;max-inline-size: 100%;margin: 0px;padding: 0px;box-sizing: border-box !important;overflow-wrap: break-word !important;outline: none 0px !important;clear: both;min-height: 1em;cursor: text;"><span style="max-inline-size: 100%;margin: 0px;padding: 0px;box-sizing: border-box !important;overflow-wrap: break-word !important;outline: none 0px !important;cursor: text;color: #595959;font-size: 12px;letter-spacing: 1px;text-indent: 0em;caret-color: red;">山东省立医院肾内科副主任</span></p><p style="text-align:center;max-inline-size: 100%;margin: 0px;padding: 0px;box-sizing: border-box !important;overflow-wrap: break-word !important;outline: none 0px !important;clear: both;min-height: 1em;cursor: text;"><span style="max-inline-size: 100%;margin: 0px;padding: 0px;box-sizing: border-box !important;overflow-wrap: break-word !important;outline: none 0px !important;cursor: text;color: #595959;font-size: 12px;letter-spacing: 1px;text-indent: 0em;caret-color: red;">主任医师，博士研究生导师</span></p><p style="text-align:center;max-inline-size: 100%;margin: 0px;padding: 0px;box-sizing: border-box !important;overflow-wrap: break-word !important;outline: none 0px !important;clear: both;min-height: 1em;cursor: text;"><span style="max-inline-size: 100%;margin: 0px;padding: 0px;box-sizing: border-box !important;overflow-wrap: break-word !important;outline: none 0px !important;cursor: text;color: #595959;font-size: 12px;letter-spacing: 1px;text-indent: 0em;caret-color: red;">中华医学会肾脏病学分会委员</span></p><p style="text-align:center;max-inline-size: 100%;margin: 0px;padding: 0px;box-sizing: border-box !important;overflow-wrap: break-word !important;outline: none 0px !important;clear: both;min-height: 1em;cursor: text;"><span style="max-inline-size: 100%;margin: 0px;padding: 0px;box-sizing: border-box !important;overflow-wrap: break-word !important;outline: none 0px !important;cursor: text;color: #595959;font-size: 12px;letter-spacing: 1px;text-indent: 0em;caret-color: red;">山东医学会肾脏病分会副主任委员</span></p><p style="text-align:center;max-inline-size: 100%;margin: 0px;padding: 0px;box-sizing: border-box !important;overflow-wrap: break-word !important;outline: none 0px !important;clear: both;min-height: 1em;cursor: text;"><span style="max-inline-size: 100%;margin: 0px;padding: 0px;box-sizing: border-box !important;overflow-wrap: break-word !important;outline: none 0px !important;cursor: text;color: #595959;font-size: 12px;letter-spacing: 1px;text-indent: 0em;caret-color: red;">山东省医学会血液净化学分会副主任委员</span></p><p style="text-align:center;max-inline-size: 100%;margin: 0px;padding: 0px;box-sizing: border-box !important;overflow-wrap: break-word !important;outline: none 0px !important;clear: both;min-height: 1em;cursor: text;"><span style="max-inline-size: 100%;margin: 0px;padding: 0px;box-sizing: border-box !important;overflow-wrap: break-word !important;outline: none 0px !important;cursor: text;color: #595959;font-size: 12px;letter-spacing: 1px;text-indent: 0em;caret-color: red;">山东省医师协会肾脏病分会常务委员</span></p><p style="text-align:center;max-inline-size: 100%;margin: 0px;padding: 0px;box-sizing: border-box !important;overflow-wrap: break-word !important;outline: none 0px !important;clear: both;min-height: 1em;cursor: text;"><span style="max-inline-size: 100%;margin: 0px;padding: 0px;box-sizing: border-box !important;overflow-wrap: break-word !important;outline: none 0px !important;cursor: text;color: #595959;font-size: 12px;letter-spacing: 1px;text-indent: 0em;caret-color: red;">山东省肾内科质量控制中心副主任兼秘书</span></p></section><section data-role="paragraph" style="font-family: 微软雅黑;"><p><br/></p></section><section data-id="106067" data-tools="135编辑器"><section style="text-align: center;margin: 10px auto;"><section style="display: inline-block;font-family: 微软雅黑;"><section style="background-color: #fac08f;padding: 7px 18px;box-sizing: border-box;"><section style="display: flex;justify-content: center;align-items: center;"><section style="box-sizing:border-box;width: 8px;height: 8px;background-color: #ffffff;border-radius: 50%;overflow: hidden;"><br/></section><section data-brushtype="text" style="font-size: 16px;letter-spacing: 1.5px;color: #fff;margin: 0 12px;"><p style="line-height: 2em;"><span style="color: #000000;"><strong><span style="font-size: 15px;letter-spacing: 2px;">效果显著、机制独特</span></strong></span></p><p style="line-height: 2em;"><span style="color: #000000;"><strong><span style="font-size: 15px;letter-spacing: 2px;color: #000000;">罗沙司他为肾性贫血患者带来获益<br/></span></strong></span></p></section><section style="box-sizing:border-box;width: 8px;height: 8px;background-color: #fff;border-radius: 50%;"><br/></section></section></section></section><section style="background-color: #fff8f8;padding: 40px 25px 25px;margin-top: -20px;box-sizing: border-box;"><section data-autoskip="1" style="text-align: justify;line-height: 1.75em;letter-spacing: 1.5px;font-size: 14px;color: #57484b;background: transparent;"><p style="text-align:justify;text-indent: 0px;line-height: 2em;"><span style="line-height: 150%;font-weight: normal;font-size: 15px;font-family: 微软雅黑, Microsoft YaHei;">既往研究已经证实，罗沙司他具有升高CKD血液透析患者的血红蛋白水平，改善贫血的作用。基于此，我院开展一项评估罗沙司他用于难治性贫血（常规EPO应用与铁剂补足情况下仍贫血）患者的疗效与安全性试验。</span></p><p style="text-align:justify;text-indent: 0px;line-height: 2em;"><br/></p><p style="text-align:justify;line-height: 2em;"><span style="line-height: 150%;font-weight: normal;font-size: 15px;font-family: 微软雅黑, Microsoft YaHei;">常规红细胞寿命的测定方法为同位素测定法，本研究采用经过国际以及中华医学会血液学分会认可的呼出气体中一氧化碳（CO）浓度来测定红细胞寿命，研究结果显示健康受试者的红细胞寿命为120天左右，终末期肾病（ESRD）患者为50天左右，而罗沙司他可以延长包括合并炎症状态、甲状旁腺亢进的ESRD患者的红细胞寿命10-20天，超过单独使用EPO患者。</span></p><p style="text-align:justify;line-height: 2em;"><br/></p><p style="text-align:justify;line-height: 2em;"><span style="line-height: 150%;font-weight: normal;font-size: 15px;font-family: 微软雅黑, Microsoft YaHei;">这一结果给予我们极大鼓舞，我们团队后续还将在相关领域展开更多探索，包括铁剂的应用、罗沙司他延长红细胞寿命的机制等相关探索，期待今后能够更多数据向领域内同道详细介绍。</span></p></section><section data-width="100%" style="box-sizing: border-box;width: 100%;height: 1px;background-color: rgb(250, 192, 143);margin-top: 20px;max-width: 100% !important;font-family: 微软雅黑;"><br/></section></section></section></section><section data-role="paragraph" style="height: 0px;overflow: hidden;font-family: 微软雅黑;"><br/></section><section data-id="106067" data-tools="135编辑器"><section style="text-align: center;margin: 10px auto;"><section style="display: inline-block;font-family: 微软雅黑;"><section style="background-color: #fac08f;padding: 7px 18px;box-sizing: border-box;"><section style="display: flex;justify-content: center;align-items: center;"><section style="box-sizing:border-box;width: 8px;height: 8px;background-color: #ffffff;border-radius: 50%;overflow: hidden;"><br/></section><section data-brushtype="text" style="font-size: 16px;letter-spacing: 1.5px;color: #fff;margin: 0 12px;"><p style="line-height: 2em;"><span style="color: #000000;"><strong><span style="font-size: 15px;letter-spacing: 2px;">三驾“马车”、全面发展</span></strong></span></p><p style="line-height: 2em;"><span style="color: #000000;"><strong><span style="font-size: 15px;letter-spacing: 2px;color: #000000;">肾内科建设稳步前行</span></strong></span></p></section><section style="box-sizing:border-box;width: 8px;height: 8px;background-color: #fff;border-radius: 50%;"><br/></section></section></section></section><section style="background-color: #fff8f8;padding: 40px 25px 25px;margin-top: -20px;box-sizing: border-box;"><section data-autoskip="1" style="text-align: justify;line-height: 1.75em;letter-spacing: 1.5px;font-size: 14px;color: #57484b;background: transparent;"><p style="text-align:justify;line-height: 2em;"><span style="line-height: 150%;font-weight: normal;font-size: 15px;font-family: 微软雅黑, Microsoft YaHei;">对于肾内科的学科建设，我想是需要“医”、“教”、“研”三方面齐头并进，才能助力临床的成长。</span></p><p style="text-align:justify;line-height: 2em;"><br/></p><p style="text-align:justify;line-height: 2em;"><span style="line-height: 150%;font-weight: normal;font-size: 15px;font-family: 微软雅黑, Microsoft YaHei;">“医”指的是在临床实践中发现问题并解决问题。本研究的开展即是在临床应用罗沙司他过程中发现了其具有增加ESRD患者红细胞寿命的特点，才吸引我们进一步深入探究，这需要细致的态度与观察。</span></p><p style="text-align:justify;line-height: 2em;"><br/></p><p style="text-align:justify;line-height: 2em;"><span style="line-height: 150%;font-weight: normal;font-size: 15px;font-family: 微软雅黑, Microsoft YaHei;">“教”指的是包括本科生、研究生以及青年医生的教学，依据不同阶段的学生给予有侧重点的培训，培养临床诊疗思维和规则意识，因材施教。</span></p><p style="text-align:justify;line-height: 2em;"><br/></p><p style="text-align:justify;line-height: 2em;"><span style="line-height: 150%;font-weight: normal;font-size: 15px;font-family: 微软雅黑, Microsoft YaHei;">“研”便是临床科研与基础科研。在临床中发现问题，开展针对性的基础科研探索来解决，实现两者地有机结合，才能更好助力全方面的成长。</span></p></section><section data-width="100%" style="box-sizing: border-box;width: 100%;height: 1px;background-color: rgb(250, 192, 143);margin-top: 20px;max-width: 100% !important;font-family: 微软雅黑;"><br/></section></section></section></section><section data-role="paragraph"><p><br/></p></section><section data-id="101146" data-tools="135编辑器" style="font-size: 15px;letter-spacing: 2px;font-family: 微软雅黑;"><section style="margin: 10px auto;"><section data-width="100%" style="box-sizing:border-box;max-width: 100% !important;overflow-y: auto;height: 219px;width: 100%;display: inline-block;"><section style="padding: 1em;box-sizing: border-box;"><section data-autoskip="1" style="box-sizing: border-box;color:#333;text-align: justify;line-height:1.75em;letter-spacing: 1.5px;font-size:14px;"><p style="text-align:left;line-height: 150%;margin-left: 0px;margin-right: 0px;"><strong style="caret-color: red;text-align: justify;"><span style="font-size: 12px;">参考文献：</span></strong></p><p style="text-align:left;line-height: 150%;margin-left: 0px;margin-right: 0px;"><br/></p><p style="line-height: normal;"><span style="font-size: 12px;caret-color: red;letter-spacing: 0px;">1、Krzyzanski W, Perez-Ruixo JJ. An assessment of recombinant human erythropoietin effect on reticulocyte production rate and lifespan distribution in healthy subjects. Pharm Res. 2007 Apr;24(4):758-72.</span></p><p style="line-height: normal;"><span style="font-size: 12px;caret-color: red;letter-spacing: 0px;">2、Yang X, Zhao B, Wang J, et al. Red blood cell lifespan in long-term hemodialysis patients treated with roxadust at or recombinant human erythropoietin. Ren Fail. 2021;43(1):1428-1436.</span></p></section></section></section></section></section></section><section data-role="paragraph"><p style="line-height:normal;"><span style="font-size: 12px;color: #7F7F7F;letter-spacing: 1px;">审批编号：CN-103160</span></p><p style="line-height:normal;"><span style="font-size: 12px;color: #7F7F7F;letter-spacing: 1px;">过期日期：2023年9月23日</span></p><p style="line-height:normal;"><span style="font-size: 12px;color: #7F7F7F;letter-spacing: 1px;">本材料由阿斯利康提供，仅供医疗卫生专业人士参考，不用于推广目的。</span><br/></p></section></section></div>