IgA nephropathy (IgAN) is an immune-mediated primary glomerulonephritis with a highly variable clinical course. Patients may present with proteinuria, hematuria, hypertension, or declining kidney function, and kidney biopsy remains necessary for diagnosis because no validated serum or urine biomarker is currently available. Importantly, clinically meaningful kidney damage may already be present by the time IgAN is recognized. Even patients historically considered at lower risk can experience progressive disease over their lifetime. For nurse practitioners and physician associates, recognizing changes in proteinuria, eGFR, hematuria, and blood pressure can help identify patients who may require further evaluation and nephrology referral.
Advances in understanding IgAN pathogenesis have led to a widely accepted four-hit model. The process begins with increased circulating galactose-deficient IgA1, followed by formation of antibodies that recognize it, development of pathogenic IgA-containing immune complexes, and deposition of those complexes in the glomerular mesangium. This deposition can trigger mesangial activation, inflammation, complement activation, fibrosis, and progressive, irreversible loss of kidney function. Growing recognition of the gut-kidney axis and the immune pathways involved in these sequential steps is also helping shape newer therapeutic strategies that target specific parts of the disease process.
Reference: Cheung CK, Mariani LH. IgA nephropathy: an overview of the disease, its pathophysiology, and involvement of the gut-kidney axis. Kidney Int Suppl (2011). 2026 Aug;15(1):3-13. doi: 10.1016/j.kisu.2026.01.003.
