Bristol Medical School, University of Bristol, Bristol, UK.
Children's Renal Unit, University of Bristol, Bristol, UK.
Nat Rev Nephrol. 2019 Dec;15(12):750-765. doi: 10.1038/s41581-019-0217-5. Epub 2019 Oct 25.
Idiopathic nephrotic syndrome (INS) describes a group of pathologies of the renal glomerulus that result in the classic triad of heavy proteinuria, oedema and hypoalbuminaemia. The disease has historically been defined by evidence of distinctive histological changes in the absence of clinical evidence of a distinct pathological driver. However, the current classification is not based on any systematic mechanistic understanding of biological processes, and therefore current treatment regimens are broad, iterative and nonspecific. Over the past 20 years delineation of the underlying biology of the target cell in INS - the glomerular podocyte - has transformed our understanding of the mechanisms that contribute to breakdown of the glomerular filtration barrier and the development of INS. It is increasingly clear that nephrotic syndrome caused by monogenic mutations is distinct from immune-driven disease, which in some cases is mediated by circulating factors that target the podocyte. The combination of systems biology and bioinformatics approaches, together with powerful laboratory models and ever-growing patient registries has potential to identify disease 'signatures' that reflect the underlying molecular mechanism of INS on an individual basis. Understanding of such processes could lead to the development of targeted therapies.
特发性肾病综合征（INS）描述了一组导致肾脏肾小球出现典型三联征（大量蛋白尿、水肿和低白蛋白血症）的病理学变化。该疾病的历史定义是基于缺乏明确病理驱动因素的临床证据的独特组织学变化。然而，目前的分类并不是基于对生物学过程的任何系统机制理解，因此目前的治疗方案广泛、迭代且非特异性。在过去的 20 年中，对 INS 靶细胞——肾小球足细胞——的潜在生物学的描述，改变了我们对导致肾小球滤过屏障破坏和 INS 发展的机制的理解。越来越明显的是，由单基因突变引起的肾病综合征与免疫驱动的疾病不同，在某些情况下，免疫驱动的疾病是由针对足细胞的循环因子介导的。系统生物学和生物信息学方法的结合，以及强大的实验室模型和不断增长的患者登记处，有可能确定反映 INS 个体基础分子机制的疾病“特征”。对这些过程的理解可能会导致靶向治疗的发展。
