New Insights on IgA Nephropathy from the Perspective of Active Lesions and Systemic Inflammatory Responses

Immunoglobulin A nephropathy (IgAN) is a chronic disease. Active disease typically presents with massive proteinuria and gross hematuria, along with renal pathological features such as mesangial cell proliferation, endothelial cell proliferation, and crescents. Active lesions may achieve remission following treatment but also can relapse at any stage of the patient's life. Systemic inflammatory markers are significantly associated with IgAN disease activity indicators. Research has found that patients with high disease activity and low chronicity are more likely to benefit from immunosuppressive therapy. We speculated that "four-hit" hypothesis in IgAN may exist as the background for the recurrence of the disease. Bacterial or viral infections and vaccinations are common mucosal triggers that may induce active lesions by activating systemic inflammatory responses. The clinical manifestations triggered by these factors are diverse, which likely reflects the complex interplay between the nature of the injury and individual patient susceptibility. In this narrative review, we explore new insight on IgAN from the perspective of active disease and systemic inflammatory responses.