IgA nephropathy (IgAN) is the usual form of glomerulonephritis worldwide; however, the pathogenesis remains complex and uncertain. The interactions of gene, immune and environment lead to the variability of IgAN clinical presentations. Except for gene, it is still a question that what kind of the external factors that may cause IgAN. We summarized exposome, microbiome and infectome may be involved in the pathogenesis of IgAN through literature. Based on the above discoveries, we proposed a hypothesis of the course of IgAN that gene determines the internal cause, while skin and mucosa inflammations are the conditions of inducing immune disorders, the low point of immune disorders and change of immune status caused by internal and external environment lead to the disease onset. Therefore, a more detailed clinical phemomics of IgAN was required to be collected for further study.© 2021. The Author(s), under exclusive licence to Springer Nature B.V.