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

Key Points Systemic glucocorticoids could reduce levels of total IgA and galactose-deficient IgA1 (Gd-IgA1) in IgA nephropathy patients, but the effect diminished after treatment discontinuation. The reduction in Gd-IgA1 levels correlates with a decrease in proteinuria in patients treated with glucocorticoids. However, the reduction in Gd-IgA1 levels at 6 months during the treatment is not associated with long-term kidney outcomes. Background The Therapeutic Effects of Steroids in IgA Nephropathy Global trial demonstrated that glucocorticoid therapy reduced proteinuria and improved kidney outcomes in patients with IgA nephropathy. Galactose-deficient IgA1 (Gd-IgA1) plays a central role in IgA nephropathy pathogenesis by promoting immune complex formation. However, the effects of glucocorticoid on pathogenic IgA levels remain unclear. This study aimed to evaluate the effect of systemic glucocorticoids on serum total IgA and Gd-IgA1 levels in patients with IgA nephropathy in the Therapeutic Effects of Steroids in IgA Nephropathy Global trial. Methods Serum samples from 137 participants in the China Cohort were collected at baseline, 6, 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 6 and 12 months. Results At 6 months, the reduced dose group showed a 27.2% (95% confidence interval, 16.4% to 36.6%) reduction in IgA and a 21.2% (10.6% to 30.6%) reduction in Gd-IgA1 compared with 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, whereas no significant correlation was observed in the placebo group. The reduction in Gd-IgA1 levels at 6 months was not associated with long-term kidney progression events ( P = 0.49). Conclusions Systemic glucocorticoids significantly reduce total IgA and Gd-IgA1 levels in IgA nephropathy compared with placebo; however, the treatment effects may diminish over time. Clinical Trial registry name and registration number: NCT01560052.