Intraglomerular Inflammation as a Guide for Mycophenolate Mofetil-Based Treatment in IgA Nephropathy

IgA nephropathy (IgAN) is the most prevalent primary glomerulonephritis worldwide, with a heterogeneous clinical course that may progress to end-stage kidney disease (ESKD) in approximately 20% of patients. Despite recent advances, including the U.S. Food and Drug Administration (FDA) approval of three novel agents, optimal therapeutic strategies remain uncertain, and access to new drugs is often limited. This underscores the need to evaluate established and widely available options such as mycophenolate mofetil (MMF). The aim of this review is to critically assess the role of MMF, either as monotherapy or in combination with systemic corticosteroids, in the treatment of IgAN based on evidence cited in the KDIGO 2024 Draft Guidelines. We analyzed seven major clinical studies-five randomized controlled trials and two long-term observational studies-with particular focus on the influence of histological activity on treatment outcomes. The Oxford classification was applied to explore whether specific histological variables correlate with prognosis and predict treatment response. Trials conducted in Chinese cohorts demonstrated significant benefits of MMF, including proteinuria reduction, delayed progression to ESKD, and improved long-term renal outcomes, particularly in patients with recent disease onset and active proliferative lesions such as endocapillary hypercellularity and crescent formation. In contrast, studies from Western populations generally failed to demonstrate comparable benefit possibly due to differences in disease chronicity, histopathological patterns, and genetic background. Overall, MMF appears most effective when initiated early and in patients with histologic evidence of intraglomerular inflammation. It may represent a viable steroid-sparing option in appropriately selected patients, particularly where access to newly approved agents is restricted. These population- and pathology-based differences highlight the need for individualized treatment decisions and further research to refine the therapeutic role of MMF in IgAN.