Recent advances in pathogenetic concepts and disease modeling of IgA nephropathy

IgA nephropathy (IgAN) is the most common form of glomerulonephritis and affected patients are at high risk of developing kidney failure over time. Recent molecular studies have led to substantial new insights into the pathogenesis of IgAN. This involves the identification of genetic risk factors in genome-wide association studies, the use of multi-omics approaches to integrate big data, the recognition of the importance of the gut-kidney axis, the role of plasma cells in the production of IgA and IgG, the potential specificity of circulating IgA for mesangial antigens, and the activation of the complement system with subsequent damage to glomerular cells. These fundamental insights were governed by the use of various animal models involving mesangial deposition of IgA, inflammation and glomerular injury. This review summarizes recently identified pathophysiological mechanisms as well as animal models of IgAN and provides an updated view on the molecular events that underlie IgAN.