How Late Is Too Late? Successful Use of Targeted-Release Budesonide in IgA Nephropathy with Estimated Glomerular Filtration Rate <30 mL/min/1.73 m2.

INTRODUCTION: IgA nephropathy (IgAN) is a common cause of chronic kidney disease (CKD) worldwide. However, patients with advanced CKD and significant fibrosis on biopsy have limited treatment options, and clinical trials studying targeted-release budesonide have excluded individuals with low estimated glomerular filtration rate (eGFR). CASE PRESENTATION: We report a case of a 36-year-old male with biopsy-proven crescentic IgAN, initially diagnosed 3 years prior, who presented with progressive renal dysfunction and persistent proteinuria despite prior treatment with immunosuppression, including corticosteroids and rituximab. At evaluation, serum creatinine was 2.86 mg/dL with an eGFR of 28 mL/min/1.73 m2, urine protein-to-creatinine ratio was 1.64 grams/day, and microscopic hematuria was present. Repeat kidney biopsy demonstrated significant chronic changes with severe interstitial fibrosis and tubular atrophy. The Oxford classification score was M1, E1, S1, T2, C1. Targeted-release budesonide was initiated, after which hematuria resolved within 1 month, proteinuria decreased significantly reaching 0.29 g/day, and kidney function improved with a serum creatinine of 2.24 mg/dL and eGFR of 38 mL/min/1.73 m2 at 8 months into treatment. The patient tolerated therapy without major adverse events. CONCLUSION: This case demonstrates clinically meaningful improvement in both proteinuria and renal function following treatment with targeted-release budesonide, despite advanced chronicity but with disease activity and low eGFR, a population that remains underrepresented in clinical trials and prospective studies. Our findings highlight the importance of repeat biopsy and future studies addressing the potential benefit of targeted-release budesonide in select patients with advanced IgAN, who may retain a therapeutically targetable inflammatory component.