#2009 Impact of systemic glucocorticoids on Gd-IgA1 levels in Immunoglobulin A Nephropathy: insights from the TESTING trial

Abstract Background and Aims Galactose-deficient IgA1 (Gd-IgA1) is a key player in the pathogenesis of Immunoglobulin A Nephropathy (IgAN), driving immune complex formation and subsequent kidney damage. The Therapeutic Effects of Steroids in IgA Nephropathy Global (TESTING) trial demonstrated that glucocorticoid therapy significantly reduced proteinuria and improved kidney outcomes in patients with IgAN. However, the effect of glucocorticoid therapy on pathogenic IgA levels remains poorly understood. This study aims to assess the impact of systemic glucocorticoids on Gd-IgA1 and total IgA levels in patients with IgAN in the TESTING trial. Method Participants with IgAN were randomised to 6–9 months of full-dose (0.6 to 0.8 mg/kg/day) or reduced-dose (0.4 mg/kg/day) oral methylprednisolone versus placebo. Serum samples from 137 participants in the China Cohort were collected at baseline, 6 months, and 12 months. Gd-IgA1 levels were quantified using the KM55 ELISA kit. A linear mixed model was used to compare the changes in Gd-IgA1 and total IgA across each treatment arm from baseline at 6 and 12 months. Results In total, 137 participants were included in this study, with 40 in the full-dose methylprednisolone group, 26 in the reduced-dose methylprednisolone group, and 71 in the placebo group. There were no statistically significant differences in baseline total IgA and Gd-IgA1 levels among the three groups. At 6 months, the reduced-dose group exhibited a significant reduction in total IgA by 27.2% (95% confidence interval [CI]: 16.4% to 36.6%) and in Gd-IgA1 by 21.2% (10.6% to 30.6%) from baseline compared to the placebo group. In the full-dose group, total IgA decreased by 34.0% (25.7% to 41.4%) and Gd-IgA1 by 42.7% (36.1% to 48.6%). By 12 months, Gd-IgA1 levels began to rise as treatment was discontinued. Gd-IgA1 levels in the reduced-dose group was marginally lower compared to placebo by 4.6% (−8.3% to 15.9%, P = 0.06), while the full-dose group maintained a significant reduction of 25.4% (16.8% to 33.1%, P < 0.001). There was no significant difference in the ratio of Gd-IgA1 to total IgA across all three groups. Conclusion Systemic glucocorticoid therapy effectively reduces total IgA and Gd-IgA1 levels in patients with IgAN compared to placebo, however the treatment effects may diminish over time.