Molecular stratification of idiopathic nephrotic syndrome

Abstract

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.