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[ADA2014]是时候让“微量白蛋白尿”退出了
——Kelly West杰出流行病学奖获奖者Andrzej S.Krolewski教授访
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作者:国际糖尿病网 2014/6/18 16:55:00    加入收藏
内容概要:受访者简介:Andrzej S.Krolewski教授是Joslin糖尿病中心遗传学和流行病学主任。他基于Joslin糖尿病中心的患者和亲属,建立了世界一流的糖尿病遗传学和流行病学研究项目。

  Andrzej S.Krolewski教授主要研究方向为糖尿病肾病和糖尿病遗传学。在今年ADA年会Kelly West杰出流行病学讲座上,他报告的题目是:是时候让“微量白蛋白尿”退出了——早期、进展性肾脏功能下降是新模式(Time to Retire “Microalbuminuria”--Early, Progressive Renal Decline Is the New Paradigm)。

  <International Diabetes>: Thank you Dr Krowlewski for joining International Diabetes here at the ADA 2014 Scientific Sessions, it is a great honor to have you with us today.  You were the lecturer for the Kelly West Award for Outstanding Achievement in Epidemiology, and your topic was “Time to Retire Microalbuminuria” and you discussed early and progressive renal decline as the new paradigm.  I know it is a very extensive lecture but could you give our audience a brief introduction to some of the key points from your research into this particular area and what you found.  Why did you choose that term “time to retire”, for microalbuminuria?

  Professor Krolewski: During my lecture I was presenting a kind of findings and conclusions of the results of a very extensive research which I have been conducting over the last 25 years at the Joslin Diabetes Center. The conclusions are such that the previously developed model, which emphasized abnormalities in albumin excretion in urine, is perhaps not the truest model.  I presented a lot of evidence that it is not true and we reported and also during my lecture I presented evidence that patients who are going to develop end stage renal disease, they start losing renal function very early disregarding whether they have microalbuminuria or not.  In that very early stage of declining renal function I am postulating that it should be the focus of research and intervention.  The practical interventions are important because at that time patients still have almost normal renal function so if we intervene at that time then we have a lot of time really to intervene and postpone the onset of end stage renal disease.  This was somehow the main thrust of my lecture and I was presenting the results from different studies we conducted, I showed that the early renal function decline can be determined by genetic factors, and also it is greatly influenced by glycemic control so that there were a lot of implications for future research and future patient care.

  《国际糖尿病》:您在Kelly West杰出流行病学奖上的演讲主题是 “是时候让微量白蛋白尿退出了”并谈及了早期进展性肾功能下降是一种新的模式。由于您的演讲涉及面很广,可否请您简要介绍一下您在该领域的研究要点及主要发现?

  Krolewski 教授:在本次演讲中,我展示了过去25年里我在Joslin糖尿病中心完成的十分广泛的研究结果的发现和结论。主要结论是,过去所强调的尿白蛋白排泄异常或许并不是最可靠的糖尿病肾病进展模型。我提出了大量证据,证实该模型的错误。我们之前报道,并且在我的演讲中也提及,许多发展为终末期肾病的患者,在很早的阶段其肾功能已经开始出现下降,无论是否伴有尿微量白蛋白。我推测,肾功能下降的极早期应该是研究和干预的重点。由于在这个时期患者的肾功能基本正常,如果我们此时进行干预就会有更多的时间治疗和延缓终末期肾病的发生,所以该期的临床干预十分重要。这就是我本次研究的主要观点。我展示了我们完成的多项研究的结果,这些研究表明,早期肾功能下降既可以取决于遗传因素,在很大程度上也会受到血糖控制的影响。这些结果对今后的研究和今后患者的治疗有很多启示。

  <International Diabetes>: I know that this is kind of more setting the basis or the foundation for future research but can you tell us now, now that if you say for example you establish someone as a person who is genetically someone who we should use an early intervention, does this genetic research also help on the treatment end for the potential for gene therapy or is it really more just in that diagnostic arena saying ‘ok this person can possible benefit’?  How does this clinically translate?

  Professor Krolewski: would like to emphasize that for diagnosis we can use many different methods. We have discoveries and we postulate the measurements of certain proteins in blood and it can be a diagnostic test to identify patients who are at risk of progressing in the future to end stage renal disease.  The genetic research is somehow important and I think in a large degree for identifying therapeutic targets because perhaps several genes are involved.  Abnormalities in those genes may affect small groups of patients.  That can not be used as a diagnostic test but the fact that some of those genes have very strong effect indicate that the pathway of the protein for coding is very important in the disease process.  Once we learn this then the pharmacopeutics, or pharmaceutical companies can take the protein and develop blockers.

  《国际糖尿病》:如果从某位患者的基因角度看应该及早进行干预,这种基因研究是否也会对基因治疗有帮助?如何将研究结果转化为临床?

  Krolewski 教授:我想强调,我们可以用各种不同的方法进行诊断。我们已经在血中检测到某些特定的蛋白,它们可以作为诊断试验识别未来有进展为终末期肾病风险的患者。基因研究很大程度上对鉴别治疗靶点很重要,因为可能多个种基因均参与发病。基因异常可能会影响一小部分患者,不能用于诊断试验,但部分基因有很大的影响,提示其蛋白编码的途径在肾病发病过程中很重要。当我们了解这些之后,相关药物治疗的人员或公司就可以针对蛋白开发出治疗药物。

  <International Diabetes>: All these new agents we see, they all started with this kind of research that we see all these new agents like DPP-4 inhibitors, SGLT-2, those pathways and the foundation for these drugs were set by people like yourself who do that kind of research.

  Professor Krolewski: Yes in my case it is for the decline in renal function.

  《国际糖尿病》:许多新药如DPP-4抑制剂、SGLT-2抑制剂等都是源于像您的这种研究模式?

  Krolewski 教授:是的,只不过我研究肾功能下降。

  <International Diabetes>: Right, renal function in your case.  You also have some collaboration with international and with the Europeans, what form is that collaboration taken and how has it helped your research?

  Professor Krolewski: We have a lot of collaboration as far as genetic research in kidney complications. We need quite a large study population to do the genetic studies and in the United States basically there is only my center, the Joslin Diabetes Center, where there is a large number of patients whom we can use for genetics.  To expand this study group or study population we collaborate with a center in Finland, we collaborate with a center in Denmark, and a center in France.  We hope that combining those resources will make it much easier to find the genes and somehow in the future possibly testing our interventions.

  <International Diabetes>: We appreciate you speaking with us today and enlightening us on your research.  Congratulations on your lecture.

  《国际糖尿病》:您在全世界和欧洲都有一些合作伙伴,它们以怎样的形式组织起来的?如何帮助您的研究?

  Krolewski 教授:我们在肾病并发症的基因研究过程中有很多合作伙伴。我们需要大量样本进行基因研究,但在美国基本上只有Joslin 糖尿病中心拥有大量可供我们进行基因研究的患者。为了扩大研究团队或者患者人数,我们分别与芬兰的一个研究中心、丹麦的一个研究中心及法国的一个研究中心合作。我们希望整合这些资源后可以更加容易地找到致病基因,然后在未来开展我们的干预研究。

  《国际糖尿病》:非常荣幸您可以与我们进行交谈并展示您的研究成果。祝贺您演讲成功。

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