Glomerular inflammation is a central driver of kidney injury in IgA nephropathy (IgAN). Within the four-hit model, galactose-deficient IgA1 and corresponding autoantibodies form pathogenic immune complexes that deposit in the glomerular mesangium, triggering mesangial cell activation, cytokine release, complement activation, and recruitment of inflammatory cells. These processes can damage neighboring endothelial cells and podocytes and contribute to progressive glomerulosclerosis and tubulointerstitial fibrosis. The alternative and lectin complement pathways appear to play particularly important roles, while the classical pathway is thought to contribute less to IgAN pathogenesis.
In practice, the treatment landscape is increasingly focused on addressing both supportive care needs and the inflammatory pathways that drive disease progression. Proteinuria and eGFR remain the main clinical tools for assessing prognosis and treatment response, but they do not directly measure active glomerular inflammation. Investigational biomarkers, including urinary sCD163, MMP-7, IL-6, and complement-related markers, may eventually help distinguish active inflammation from irreversible damage and guide more individualized therapy, but none has yet replaced established clinical criteria. As corticosteroid-based approaches and therapies targeting complement and BAFF/APRIL signaling continue to evolve, better biomarkers may become increasingly important for identifying which patients are most likely to benefit from specific approaches and for monitoring response over time.
Reference: Yau K, Reich HN. How should we measure and interpret glomerular inflammation and what is the best anti-inflammatory approach in IgA nephropathy? Nephrol Dial Transplant. 2026 Feb 23;41(Suppl 1):i15-i26. doi: 10.1093/ndt/gfaf135.
Link: https://academic.oup.com/ndt/article/41/Supplement_1/i15/8223402?login=true
