The outcome of IgAN: a time of reflection in the perspective of new opportunities.

The prognosis of IgA nephropathy (IgAN) has long been uncertain due to its slow progression rate. For this reason, it has been considered a relatively benign disease with limited need for specific treatment. Recent registry data suggest that up to 75% of patients progress to kidney failure within 25 years. Moreover, the average age at the time of kidney biopsy has progressively increased, suggesting that one possible reason for worsening outcomes is the change in patient characteristics. Consequently, delayed kidney biopsies and thus later-stage diagnoses may reduce treatment efficacy and expose more patients to treatment-related adverse events. Traditional therapeutic options, including renin-angiotensin system (RAS) blockers and corticosteroids, have shown limited success in achieving complete remission. Newer agents, such as budesonide, sodium-glucose co-transporter-2 (SGLT2) inhibitors, and sparsentan, have shown improved proteinuria reduction but are still far from achieving remission. The efficacy of corticosteroids appears to depend on the degree of residual kidney function at the time of treatment initiation, with better outcomes observed in patients with higher baseline kidney function. The development of novel therapeutic agents, together with a deeper understanding of IgAN immunopathogenesis and chronic kidney disease (CKD), is reshaping treatment paradigms. As recommended by the new Kidney Disease: Improving Global Outcomes (KDIGO) guidelines, treatment strategies now need to involve a combination approach targeting both immune dysregulation and CKD progression.