#723 Predictive value of Gd-IgA1, poly-IgA in the treatment of IgA nephropathy with targeted−release formulation budesonide

Abstract Background and Aims Targeted release formulation (TRF)-budesonide (Nefecon), targeting the production of galactose-deficient IgA1 (Gd-IgA1) and IgA immune complex formation, has been approved for the treatment of IgA nephropathy (IgAN). In this study we aim to investigate whether these biomarkers can predict the clinical response to Nefecon therapy. Method Plasma samples from eight Nefecon-treated IgAN patients were collected at each regular clinic follow-up visit. We measured the levels of Gd-IgA1 and poly-IgA, analyzing the association between their baseline levels or changes and proteinuria reduction. Results Nefecon treatment significantly reduced proteinuria with a notable reduction after 5 months of therapy. The alterations of proteinuria were 18%, −33%, −36%, and −39% at 3, 6, 9, and 12 months, respectively. While plasma levels of Gd-IgA1, poly-IgA and total IgA decreased within the first 2 months with changes in Gd-IgA1 of −6%, −34%, −17%, and −34%; in poly-IgA of −8%, −24%, −13%, and −18%; and in total IgA of −3%, −21%, −16%, and −29% at 1, 2, 3, and 9 months, respectively. Poly-IgA reductions correlated with proteinuria alterations (P = 0.01). Importantly, the early reduction in poly-IgA during the first 2 months was associated with proteinuria reduction at the final visit (R2 = 0.59, P = 0.07). Similar trends were observed for Gd-IgA1 or total IgA while not reaching statistical significance. Conclusion The early changes in Gd-IgA1 or poly-IgA during the first two months, especially poly-IgA, were associated with future proteinuria reduction. These findings suggest that Gd-IgA1 and poly-IgA may serve as biomarkers for Nefecon response.