LAUSR

Idiopathic immunoglobulin-A (IgA) nephropathy is a primary glomerulonephritis with varying clinical presentations. Treatment regimens are often poorly tolerated and yield variable results. The NEFIGAN Trial (targeted-release budesonide vs. placebo in patients with IgA nephropathy) demonstrated that targetedrelease-formulation budesonide (TRF-budesonide), in conjunction with optimal renin-angiotensin system blockade, safely reduced proteinuria in adults with IgA nephropathy. The authors suggest that TRF-budesonide targets the high density of Payer’s patches in the ileum, which suppresses the dysfunctional mucosal immune system. To our knowledge, this report details the first successful trial of this therapy in a paediatric patient. An 8-year-old boy was diagnosed with IgA nephropathy following an episode of haematuria. At presentation, his serum creatinine was 79 μmol/L, and his urinary protein-to-creatinine ratio (uPCR) was >800 mg/mmol. A kidney biopsy demonstrated features of IgA mesangioproliferative glomerulonephritis with focal segmental sclerosis (55%) and crescents (25%) (M1, E1, S1, T0). He received 25 mg/kg of pulse methylprednisolone daily for 3 days, followed by a tapering course of prednisolone over 6 months. He continued to have synpharyngitic, macroscopic haematuria and exacerbations of nephrotic-range proteinuria despite adding 15 mg of enalapril daily. At 3.5 years postdiagnosis, he underwent repeat kidney biopsy, which showed active mesangioproliferative IgA nephropathy, worsening sclerosis (61%), new tubular atrophy (30%) and crescents (25%) (M1, E1, S1, T1). Despite further courses of oral prednisolone (1 mg/kg/day with slow tapering regimes) and the addition of 75 mg of irbesartan daily, his creatinine increased to 90 μmol/L and uPCR to 520 mg/mmol. Now 12 years old and demonstrating persistent nephrotic-range proteinuria, he was commenced on a trial of 3 mg of TRF-budesonide daily, which increased to 6 mg daily after 4 weeks. He remained on enalapril and irbesartan during this 6-month trial. He had a positive response, with his uPCR falling from 520 mg/mmol to 69 mg/mmol and serum creatinine normalising to 69 μmol/L. The dose of TRFbudesonide was well tolerated, and no side effects were reported. Following this successful trial, we have commenced a weaning regime of 3 mg daily for 6 months, with second-daily dosing planned thereafter. The NEFIGAN trial demonstrated dose-dependent results; adults treated with 8 mg/day had stable uPCR, yet the 16 mg/day group showed significant improvement. In our paediatric patient, a targeted treatment dose of 6 mg daily was used, with a formulation approved by our centre’s Drug and Therapeutics Committee for the treatment of inflammatory bowel disease. It is possible that higher dosing may have resulted in more rapid improvement or conversely impeded treatment due to side effects. This case suggests that localised steroid formulations may have a role in treating IgA nephropathy in children. Ultimately, trial data is required to confirm that the NEFIGAN results can be safely generalised to children.