RealxWorld Effectiveness of Targeted-Release Budesonide in IgA Nephropathy with Near-Universal SGLT2 Inhibitor Use

BACKGROUND: IgA nephropathy (IgAN) is the most common primary glomerulonephritis worldwide and a leading cause of end-stage kidney disease. Targeted-release formulation (TRF) budesonide demonstrated significant reductions in proteinuria and attenuation of estimated glomerular filtration rate (eGFR) decline in the randomised NefIgArd trial. However, real world effectiveness and tolerability in routine clinical practice remain less well characterised. METHODS: We conducted a retrospective cohort study of all patients with biopsy-proven IgAN initiated on TRF budesonide between 1st January 2024 and 31st July 2025 at a single renal centre in the United Kingdom, with follow-up until 31st January 2026. Outcomes were change in urine protein-to-creatinine ratio (UPCR) and eGFR from baseline to 3, 6 and 9 months and to latest follow-up, assessed within patients using the Wilcoxon signed-rank test. Intention-to-treat (all 33 patients commencing therapy) and per-protocol (≥6 months of therapy and not switched directly from modified-release budesonide) analyses were performed. Pre- and post-treatment eGFR slopes were compared using linear mixed-effects models, and a historical comparator cohort matched on baseline UPCR was drawn from the Salford Kidney Study; both are reported as exploratory. RESULTS: Median age was 44 (IQR 37-60) years, baseline UPCR 212 (133-289) mg/mmol, and eGFR 48 (30-61) mL/min/1.73 m². Renin-angiotensin system (RAS) inhibitor and sodium-glucose cotransporter-2 (SGLT2) inhibitor use were 94% and 91%, respectively. At latest follow-up (median 11.2 months after treatment initiation), UPCR decreased by 60% (IQR 31-71%) in the ITT cohort (p < 0.001) and 57% (IQR 26-72%) in the PP cohort (p < 0.001). eGFR was stable across the treatment period, with no significant change from baseline at nine months or at latest follow-up. Pre- to post-treatment slope comparison was confounded by initiation of SGLT2 inhibitor therapy within the pre-treatment observation window and is reported as exploratory. An adverse effect was recorded in 9 of 33 patients (27%). Seven patients (21%) discontinued treatment, six for non-serious adverse effects and one for a serious adverse event (staphylococcal septicaemia requiring hospital admission). CONCLUSIONS: In a real-world IgAN cohort with near-universal RAS and SGLT2 inhibitor use, TRF budesonide was associated with substantial proteinuria reduction, additive to optimised background therapy. eGFR was stable over the treatment period. Slope-based analyses could not be interpreted, because background SGLT2 inhibitor therapy was initiated within the pre-treatment observation window in nearly every patient. Discontinuation for adverse effects was more frequent than in trials; adverse event frequencies are not directly comparable given retrospective ascertainment.