Mischak Harald
Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow G12 8TA, UK Mosaiques Diagnostics GmbH, Hannover D-30625, Germany.
Nephrol Dial Transplant. 2015 Apr;30(4):532-7. doi: 10.1093/ndt/gfv046.
In this article, the benefits of urinary proteomics in comparison with kidney biopsy are discussed. The majority of urinary proteins are generated by the kidney, hence the urinary proteome holds substantial information on the kidney, and assessment of the urinary proteome could be considered a 'liquid biopsy'. The main question is how well the information contained in the urinary proteome can be assessed today, if it is ready to be routinely used, and what are the advantages and possible disadvantages in comparison with current standards. Since chronic kidney disease (CKD) is by far the largest area in nephrology based on the number of patients affected, the focus of this article is on CKD. Substantial progress was made in the last decade in urinary proteomics, and today we have comparable urinary proteome datasets of tens of thousands of subjects available. Clinical proteomics studies in CKD including close to, or even exceeding, 1000 subjects have recently been published, demonstrating a benefit over the current state-of-the-art in diagnosis and especially prognosis. The first large multicentric randomized controlled intervention trial aiming at preventing CKD by employing urinary proteomics-guided intervention has been initiated recently. These data provide ample evidence for the utility and value of urinary proteomics in nephrology. A further consideration is that the purpose of the biopsy, be it 'liquid' or 'solid', is to guide intervention. However, essentially all drug targets are proteins, not microscopic structures. Therefore, obtaining information on the proteome to guide intervention appears to be the most appropriate approach. Presenting more detailed evidence, I argue that urinary proteome analysis can, in most cases, be employed to guide therapeutic intervention, can be repeated multiple times as it is without any direct risk or discomfort and can be considered as a liquid biopsy.
在本文中,我们讨论了尿蛋白质组学相对于肾活检的优势。大多数尿蛋白由肾脏产生,因此尿蛋白质组包含了大量有关肾脏的信息,对尿蛋白质组的评估可被视为一种“液体活检”。主要问题在于,如今尿蛋白质组中所包含的信息能在多大程度上得到评估,它是否已准备好可常规使用,以及与当前标准相比有哪些优缺点。鉴于慢性肾脏病(CKD)是目前肾脏病学领域中受影响患者数量最多的领域,本文重点关注CKD。过去十年尿蛋白质组学取得了重大进展,如今我们拥有数万名受试者的可比较尿蛋白质组数据集。近期发表的CKD临床蛋白质组学研究纳入了近1000名甚至更多受试者,显示出其在诊断尤其是预后方面优于当前的先进技术。最近启动了第一项大型多中心随机对照干预试验,旨在通过采用尿蛋白质组学指导的干预措施来预防CKD。这些数据充分证明了尿蛋白质组学在肾脏病学中的实用性和价值。另一个需要考虑的问题是,活检的目的,无论是“液体”活检还是“实体”活检,都是为了指导干预。然而,基本上所有的药物靶点都是蛋白质,而非微观结构。因此,获取蛋白质组信息以指导干预似乎是最合适的方法。给出更详细的证据后,我认为在大多数情况下,尿蛋白质组分析可用于指导治疗干预,由于其没有任何直接风险或不适,可多次重复进行,并且可被视为一种液体活检。