Lindenmeyer Maja T, Kretzler Matthias
Nephrological Center, Medical Clinic and Policlinic IV, University of Munich, Munich, Germany.
Department of Medicine, University of Michigan, Ann Arbor, MI, USA.
Pflugers Arch. 2017 Aug;469(7-8):1021-1028. doi: 10.1007/s00424-017-2006-y. Epub 2017 Jun 29.
Chronic kidney disease has severe impacts on the patient and represents a major burden to the health care systems worldwide. Despite an increased knowledge of pathophysiological processes involved in kidney diseases, the progress in defining novel treatment strategies has been limited. One reason is the descriptive disease categorization used in nephrology based on clinical findings or histopathological categories irrespective of potential different molecular disease mechanisms. To accelerate progress toward a targeted treatment, a definition of human disease extending from phenotypic disease classification to mechanism-based disease definitions is needed. In recent years, we have witnessed a major transition in biomedical research from a single gene research to an information rich and collaborative science. Tissue-based analysis in renal disease allows to link structure to molecular function. In our review, we introduce the concept of precision medicine in nephrology, describe several large cohort studies established for molecular analysis of kidney diseases, and highlight examples of renal biopsy-driven target identification by integrative systems biology approaches. Furthermore, we give an outlook on how the new disease definitions can be used for patient stratification in clinical trial design. Finally, we introduce the concept of an informational commons of renal precision medicine for joint analyses of large-scale data sets in renal failure.
慢性肾脏病对患者有严重影响,也是全球医疗保健系统的一项重大负担。尽管人们对肾脏疾病所涉及的病理生理过程的认识有所增加,但在确定新的治疗策略方面进展有限。原因之一是肾脏病学中基于临床发现或组织病理学分类的描述性疾病分类,而不考虑潜在的不同分子疾病机制。为了加快靶向治疗的进展,需要一种从表型疾病分类扩展到基于机制的疾病定义的人类疾病定义。近年来,我们见证了生物医学研究从单一基因研究向信息丰富的协作性科学的重大转变。肾脏疾病的组织分析能够将结构与分子功能联系起来。在我们的综述中,我们介绍了肾脏病学中的精准医学概念,描述了为肾脏疾病分子分析而开展的几项大型队列研究,并强调了通过综合系统生物学方法进行肾活检驱动的靶点识别的实例。此外,我们展望了新的疾病定义如何用于临床试验设计中的患者分层。最后,我们介绍了肾脏精准医学信息共享库的概念,用于对肾衰竭中的大规模数据集进行联合分析。