Current IgA nephropathy (IgAN) management relies largely on proteinuria, eGFR, blood pressure, biopsy findings, and the Oxford MEST-C classification, but these measures do not directly identify the molecular pathways driving disease in an individual patient. Proteomic research is beginning to fill that gap by revealing reproducible patterns of complement activation, immune signaling, extracellular matrix remodeling, and metabolic dysfunction across plasma, urine, and kidney tissue. Plasma proteomics may capture systemic immune and complement activity, urinary proteomics provides a noninvasive window into ongoing intrarenal injury, and tissue proteomics can directly characterize compartment-specific disease mechanisms. Among these approaches, urinary proteomics is the most clinically advanced. The IgAN237 urinary peptide classifier improved prognostic discrimination beyond traditional clinical factors, increasing AUC from 0.72 to 0.89 in a multicenter study.
The long-term goal is to move from treating IgAN as a single disease toward identifying molecular endotypes, such as complement-dominant, immune-inflammatory, fibrotic/remodeling, or metabolic disease, that could eventually guide mechanism-based therapy. However, proteomics is not yet ready to direct routine treatment decisions: no validated plasma proteomic test currently predicts response to a specific IgAN therapy, and most studies remain small, cross-sectional, methodologically heterogeneous, and insufficiently validated. The authors emphasize that future progress will require standardized testing, multicenter validation, longitudinal sampling, and prospective trials showing that proteomic-guided treatment improves outcomes. For now, proteomics is best viewed as a promising complement to clinical assessment and kidney biopsy, with potential to refine risk stratification and precision treatment as evidence matures.
Reference: Delrue C, Marzocco S, Moresco RN, Speeckaert MM. Plasma proteomics in IgA nephropathy: from circulating biomarkers to molecular endotypes. Cells. 2026 Jul 30;15(15):1373. doi: 10.3390/cells15151373. PMID: 42587782; PMCID: PMC13464405.
