Efficacy and safety of budesonide for the treatment of IgA nephropathy: a systematic review and meta-analysis.

BACKGROUND

Targeted-release budesonide (TRF-budesonide) is a therapy developed to deliver corticosteroid to ileal Peyer's patches and has demonstrated efficacy in randomized trials (NEFIGAN, NefIgArd) for patients with immunoglobulin A nephropathy (IgAN). We performed a systematic review and meta-analysis to evaluate the efficacy and safety of budesonide formulations in IgAN.

METHODS

We searched PubMed, Embase, and Cochrane through September 10, 2025. Eligible studies assessed budesonide in biopsy-proven IgAN. Outcomes included change in eGFR, percentage and absolute change in urine protein-to-creatinine ratio (UPCR), and adverse events. Random-effects meta-analyses were performed.

RESULTS

Nine studies (total N = 465; two RCTs) were included. In the comparative analysis of placebo-controlled trials, TRF-budesonide significantly attenuated eGFR decline compared to placebo (weighted mean difference [WMD] 4.53 mL/min/1.73 m2; 95% CI 3.08-5.99). In the single-arm analysis assessing absolute change from baseline, the pooled mean eGFR increase was 3.07 mL/min/1.73m2 (95% CI 0.12-6.03). Regarding proteinuria, TRF-budesonide significantly reduced UPCR compared to placebo (percentage change MD - 28.96%; 95% CI - 45.94 to - 11.99). Safety analysis showed budesonide was associated with a higher risk of adverse events versus placebo (RR 1.18; 95% CI 1.01-1.38). In uncontrolled cohorts, pooled adverse event rates were 40% for TRF-budesonide and 44% for enteric-coated formulations.

CONCLUSIONS

Current evidence indicates that TRF-budesonide improves kidney function and reduces proteinuria in adults with IgAN, but conclusions are tempered by limited RCT data, heterogeneity, short follow-up, and sparse histologic end points. Larger, longer randomized trials with standardized outcomes are needed to confirm long-term benefit and safety.