Real-world multicenter evidence on Nefecon for attenuating proteinuria and kidney function decline in IgA nephropathy.

INTRODUCTION: Targeted-release budesonide (Nefecon) has demonstrated efficacy in IgA nephropathy (IgAN) trials, yet real-world data across disease severity spectrum remains limited. METHODS: This multicenter, retrospective cohort study included 148 biopsy-proven IgAN adults (Nefecon =79; RASi =69). Primary endpoints were 9-month changes in proteinuria and eGFR. Mahalanobis distance matching within propensity score calipers addressed baseline imbalances. Response dynamics and safety were secondarily evaluated. RESULTS: Despite worse baseline eGFR (median 54.2 vs. 85.3 mL/min/1.73m²; P < 0.001) and more severe pathological lesions in the Nefecon group compared to RASi group, Nefecon was associated with greater proteinuria reduction (-1.25 vs. -0.58 g/24h; P < 0.001) and favorable eGFR trajectories (+2.7 vs. -11.2 mL/min/1.73m²; between-group difference 13.9 mL/min/1.73m2; 95% CI 12.7 to 15.1; P <0.001), findings remained largely consistent after Mahalanobis distance matching adjustment. Complete and partial remission rates were higher (29.1% and 54.2% vs. 10.1% and 23.2%; P < 0.001), with 59.5% achieving ≥50% proteinuria reduction versus 21.7% (RR 2.70, 95% CI 1.62-4.51). Treatment effects varied by baseline disease severity. Enhanced antiproteinuric efficacy was observed in patients with proteinuria >1.5 g/24h (interaction P = 0.003), while kidney function preservation was most pronounced in those with eGFR <60 mL/min/1.73m². Notably, 51.1% of initial non-responders achieved remission by 9 months, with complete remission rates increasing 4.6-fold over time. Adverse events were consistent with corticosteroid exposure; menstrual disturbance occurred in 39.5% of females. Serious adverse events were rare (2.5%). CONCLUSION: This real-world observational analysis shows Nefecon associated with improved proteinuria and eGFR outcomes across IgAN severity, extending randomized trial evidence to patients with advanced CKD and revealing substantial delayed response.