Real-World Effectiveness of Targeted-Release Budesonide in IgA Nephropathy with Near-Universal SGLT2 Inhibitor Use.

Abstract

Introduction: 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. We report real-world outcomes following initiation of TRF budesonide in a tertiary renal centre.

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 UK, with follow-up until 31st January 2026. Outcomes were changes in urine protein-to-creatinine ratio (UPCR) and eGFR from baseline to 3, 6, and 9 months and to the latest follow-up, assessed within patients using the Wilcoxon signed rank test. Intention-to-treat (ITT; all 33 patients commencing therapy) and per-protocol (PP; ≥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: Thirty-three patients commenced TRF budesonide, of whom 23 met PP criteria. 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 the 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 9 months or at the latest follow-up in either analysis set. 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, 6 for non-serious adverse effects and 1 for a serious adverse event (staphylococcal septicaemia requiring hospital admission); treatment was temporarily suspended in 1 further patient.

Conclusion: 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, though symptoms were generally mild; adverse event frequencies are not directly comparable given retrospective ascertainment.