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

Abstract

Background: Targeted release formulation (TRF) budesonide (Nefecon), targeting galactose-deficient immunoglobulin A1 (Gd-IgA1) production and IgA immune complex formation, has been approved for IgA nephropathy (IgAN) treatment. In this study we explored whether early changes in these biomarkers can predict the clinical response to Nefecon therapy.

Methods: Plasma samples from 27 IgAN patients treated with Nefecon and followed at least 6 months were collected during routine visits. We measured the levels of Gd-IgA1 and poly-IgA during the treatment, analysing the association between their baseline levels or changes and proteinuria reduction.

Results: The mean proteinuria level was 1.3 ± 0.8 g/day and the estimated glomerular filtration rate was 47.1 ± 21.7 ml/min/1.73 m² at baseline. During the follow-up, proteinuria slowly decreased, with alterations of -0.12 g/day, -0.42 g/day, -0.58 g/day and -0.86 g/day at 3, 6, 9 and 12 months, respectively. The plasma levels of Gd-IgA1, poly-IgA and total IgA decreased after Nefecon treatment, with an obvious decrease at 2 months in Gd-IgA1 by -1067.3 ng/ml and poly-IgA by -1.18 mg/l. All biomarker reductions were strongly associated with a proteinuria decrease (P < .0001). Importantly, the early reduction in poly-IgA during the first 2 months was associated with a proteinuria reduction at 6 months (R = 0.47, P = .01). Similar trends were observed for Gd-IgA1, though not statistically significant.

Conclusions: The early changes in Gd-IgA1 or poly-IgA, especially poly-IgA, were associated with future proteinuria reduction, supporting the potential of Gd-IgA1 and poly-IgA as biomarkers for predicting Nefecon response in IgAN.