IgA Nephropathy Proteome Profiling

IgA nephropathy (IgAN) is a heterogeneous disease, which poses a series of challenges to accurate diagnosis and personalized therapy. Here, we present a systematic quantitative kidney tissue proteome atlas across 19 tumor-adjacent normal kidney tissues, 12 membranous nephropathy (MN) samples and 59 biopsies from IgAN patients. Consensus sub-clustering of proteome profiles divided IgAN into three subtypes (IgAN-C1, C2 and C3). Compared to IgAN-C2, the IgAN-C1, and C3 subtypes had a different regulating mechanism and exhibited higher levels of complement activation, more severe mitochondrial injury, and more significant extracellular matrix accumulation. Additionally, IgAN-C1 and C3 had worse clinical outcomes than C2 (30% serum creatinine increase as the end point, P<0.01). Overall, the novel proteomic prognostic subtyping of IgAN could help us understand the heterogeneity of IgAN and improve clinical outcomes.