Role of Systemic Glucocorticoids in Reducing IgA and Galactose-Deficient IgA1 Levels in IgA Nephropathy.

The Therapeutic Effects of Steroids in IgA Nephropathy Global (TESTING) trial demonstrated that glucocorticoid therapy reduced proteinuria and improved kidney outcomes in patients with Immunoglobulin A Nephropathy (IgAN). Galactose-deficient IgA1 (Gd-IgA1) plays a central role in IgAN pathogenesis by promoting immune complex formation. However, the effects of glucocorticoid on pathogenic IgA levels remain unclear. This study aimed to evaluate the impact of systemic glucocorticoids on serum total IgA and Gd-IgA1 levels in patients with IgAN in the TESTING trial. Serum samples from 137 participants in the China Cohort were collected at baseline, six, and 12 months. We measured the levels of total IgA and Gd-IgA1. The association between the changes in these markers and proteinuria reduction was analyzed. A linear mixed model was used to compare the changes in total IgA and Gd-IgA1 across each arm from baseline at six and 12 months. At six months, the reduced-dose group showed a 27.2% (95% CI: 16.4% to 36.6%) reduction in IgA and a 21.2% (10.6% to 30.6%) reduction in Gd-IgA1 compared to the placebo group. The full-dose group exhibited reductions of 34% (25.7% to 41.4%) and 42.7% (36.1% to 48.6%), respectively. At 12 months, Gd-IgA1 decrement in the reduced-dose group were similar compared to placebo by 4.6% (-8.3% to 15.9%, P = 0.47), while the full-dose group maintained a significant reduction of 25.4% (16.8% to 33.1%, P < 0.001). A positive correlation was found between changes in total IgA, Gd-IgA1 and proteinuria reduction in the methylprednisolone groups, while no significant correlation was observed in the placebo group. The reduction in Gd-IgA1 levels at six months was not associated with long-term kidney progression events (P = 0.49). Systemic glucocorticoids significantly reduce total IgA and Gd-IgA1 levels in IgAN compared to placebo, however the treatment effects may diminish over time.