一个new articleabout Focal Segmental Glomerulosclerosis (FSGS) – a progressive kidney disease – was published inBMC Medicinetoday. We spoke to Jochen Reiser, an expert in the field, and Chairman of Medicine at Rush University, Chicago, to find out more about FSGS and what these latest results add to our understanding.

What exactly是Primary Focal Segmental Glomerulosclerosis (FSGS)?

简单地说，FSG是一种渐进的肾脏疤痕疾病。其发展的原因可能是几个，并且是肾脏内部或外部的。FSG可以在30％或更多病例中肾脏移植后复发。鉴于复发性FSGS疾病的迅速诱导，科学家和临床医生怀疑存在一种所谓的“循环因子”，它存在于接受者的血液中，并损害了新肾脏。

FSG早期的主要损伤靶标是一个称为足细胞的细胞。足细胞形成肾脏过滤屏障的中心部分，如果失败，它们会失去典型的“章鱼状”结构，并允许血浆蛋白从血液传递到尿液（蛋白尿）。

蛋白尿的临床后果是多种多样的，包括心血管疾病的风险增加以及进行性肾脏疾病，最终导致肾功能的丧失以及透析或肾脏移植的需求。

What is the history behind suPAR as a marker of FSGS, and what is the relevance of this current work?

我的实验室多年来一直在研究足细胞的行为。我们发现它们是动态的，而不是静态细胞。控制其过程动力学的程序通过整联蛋白，可能是活跃或不活动的细胞矩阵锚进行调节。

Integrins can associate with the urokinase receptor expressed together with integrins in the same cell or can reach the podocyte from the blood stream in its soluble form called suPAR.

The initial paper describing interactions of the urokinase receptor (uPAR) with integrins came from Harold Chapman’s group at UCSF and was1996年发表在科学上。之后，我们找到足细胞中的UPAR与整联蛋白有关。

后续研究在我们的实验室中，可以将supar鉴定为FSG中的循环因子。它结合并激活了足细胞α3整合素受体，从而引起足细胞运动障碍和早期FSG。

What further research needs to be done?

我们鉴定出FSG患者血液中的高血清SUPAR水平。鉴于知道Supar在炎症和某些癌症等其他条件下也可以提高SUPAR，因此很明显的是广告ELISA（（an assay) is not well suited for a single or screening test in a diverse population.

The test is helpful in patients with normal or mildly reduced kidney function and those with an existing diagnosis of FSGS in the sense of being a risk status marker. suPAR in the blood in most, but not all studies, correlates with renal function, but the current ELISA cannot differentiate simple accumulation from pathological production in FSGS in advanced renal failure.

这种困境的原因也在于，ELISA识别糖基化的supar，而不是[或不良] supar，而糖基化和/或作为片段降低。

We also now know that different suPAR types have different effects on integrins. We can test this with novel cell models and hopefully soon with a specific suPAR ELISA for FSGS. Parts of these detailed studies will be published soon.

Huang等人的论文是什么BMC Medicine？

本文描述了当前可用的ELISA在尿液中的使用the results are stunning。分析了64例肾小球疾病患者的尿液中的supar水平。FSGS患者的SUPAR主要升高并指示为FSG，与肾功能无关。

我怀疑FSG中supar型的生化特性使得它们允许优先排泄或缺乏重吸收。它确实建立了这样一个想法，即FSG中的supar不仅升高，而且升高和不同。因此，这与其他可能出现高supar且没有相关肾脏疾病的疾病不同。

The results from这张纸suggest we might be able to use the current ELISA by using urine as the kidney leaks out the most toxic suPAR. Furthermore, the authors show that suPAR in FSGS urine can activate podocyte integrin, demonstrating that the suPAR which is measured is relevant to the causes of the disease.

How will this work influence clinical practice?

首先，它将刺激更多的研究，并允许生物标志物与病理学的结合，这是肾脏科的新方向，非常需要。

Second, a device that removes all suPAR forms is in clinical development and is scheduled for testing in late 2015. Specific removal of suPAR in patients with recurrent FSGS will give the most definitive answer to whether suPAR is a cause or an effect of renal disease.

第三,肾脏学研究是一个缺点ervative field. Diversifying ideas, and developing and embracing new concepts does not always come easily. I’m happy to see that suPAR and FSGS is now its own field with close to 50 publications. Only through the collective work of others, will we achieve new goals and develop better treatments.

How will nephrology look in 20 years?

这是一个棘手的问题。病理学和分子途径和遗传学都将结合在一起，从而获得高度特异性和有针对性的治疗。我们可能会谈论类似于“活检的FSG”，具有APOL1负面状态，NPHS2中的Supar阳性，隐性突变，在1型糖尿病患者中。然后，治疗将具有多个组件，并且可能比今天更有效。