How do various therapeutic approaches for IgA nephropathy target the different stages of the four-hit hypothesis?

Based on our mechanistic understanding and some limited biomarkers, we think that ACEI, ARB, SGLT2i, endothelin antagonists like sparsentan, and complement inhibitors like iptacopan all act on the final "Hit 4" of glomerular inflammation. This points out that Hit 4 is actually quite complex! It invo...

• Decreased production of galactose-deficient IgA: delayed-release budesonide
• Decreased glomerular inflammation from immune complex (Gd-IgA - IgG) deposition: glucocorticoids, iptacopan
• Decreased glomerular scarring, hyperfiltration, proteinuria, tubulointerstitial fibrosis: RAASi, SGLT2i, DEARA like...