Pathophysiology of IgAN

This episode focuses on the underlying biology of IgA nephropathy, particularly the “multi-hit hypothesis.” The panel explains that the disease is driven not by a single event but by several interconnected immune steps, beginning with the production of galactose-deficient IgA1, followed by the formation of circulating autoantibodies, immune complex deposition in the kidney, and subsequent inflammatory injury. They discuss how each of these biological stages represents a potential therapeutic target. The clinicians emphasize that understanding the mechanism helps guide treatment choices, especially as newer agents are designed to intervene earlier in the disease pathway. They contrast older, broad immunosuppressive drugs with emerging therapies that more selectively modulate specific immune steps. This mechanistic framing helps reinforce why some patients continue to worsen even when proteinuria is controlled: the deeper immune dysregulation may remain active. The segment helps connect pathophysiology directly to clinical decision-making.