Abstract
INTRODUCTION: IgA nephropathy (IgAN) is a leading cause of kidney failure, characterized by galactose-deficient IgA1 (Gd-IgA1) deposition and immune complex formation. Aberrant trafficking of IgA+ plasma cells and autoantibody production (IgG or IgA) contribute to disease pathogenesis. Proteasome inhibitors such as bortezomib may modulate B or plasma cell activity and reduce pathogenic antibody production. METHODS: This open-label, prospective, uncontrolled trial evaluated bortezomib in adults with biopsy-confirmed IgAN, proteinuria > 1.5 g/d, and estimated glomerular filtration rate (eGFR) ≥ 30 ml/min per 1.73 m(2) despite optimized care. Patients received 4 to 8 doses of i.v. bortezomib at 1.1 to 1.3 mg/m(2) per dose. The primary end point was achieving 24-hour proteinuria (24 h-UP) < 300 mg/24 h at 12 months. Secondary end points included changes in eGFR and adverse event monitoring. RESULTS: Sixteen patients completed the study. Median time from diagnosis to treatment was 63 months (range: 10-192). Baseline proteinuria was 2.719 g/24 h (95% confidence interval [CI]: 2.169-3.408), and mean eGFR was 51.1 ml/min per 1.73 m(2) (95% CI: 41.3-60.8). At 12 months, proteinuria decreased by 44.67%, with 6.25% achieving complete remission and 43.75% achieving ≥ 50% reduction. Proteinuria reduction persisted at 24 months (mean: 1.411 g/24 h: 48.09% reduction). The annual eGFR slope was -4.275 ml/min per 1.73 m(2). No serious treatment-related adverse events were reported. CONCLUSION: Short course bortezomib therapy led to sustained proteinuria reduction in patients with IgAN, with an acceptable safety profile. These results support further evaluation in larger, controlled trials.