Work

Prospective Pilot Study of Plasma Cell–Targeted Therapy With Bortezomib in Refractory IgA Nephropathy

Year: 2025

Type: article

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 like bortezomib may modulate B/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/day, and eGFR ≥30 mL/min/1.73 m 2 despite optimized care. Patients received 4-8 doses of intravenous bortezomib at 1.1-1.3 mg/m 2 per dose. The primary endpoint was achieving 24-hour proteinuria <300 mg/24h at 12 months. Secondary endpoints 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/24h (95% CI: 2.169–3.408), and mean eGFR was 51.1 mL/min/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 a ≥50% reduction. Proteinuria reduction persisted at 24 months (mean 1.411 g/24h: 48.09% reduction). The annual eGFR slope was –4.275 mL/min/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. Trial Registration The trail was registered at the ClinicalTrials.gov (NCT05383547).

Source: Kidney International Reports

DOI: 10.1016/j.ekir.2025.06.006

Authors: Li Lin, Hong Ren, Xiao Li, Jingyuan Xie, Nan Chen

Institutions: Shanghai Jiao Tong University, Ruijin Hospital

Language: English

Topic: Renal Diseases and Glomerulopathies

Subfield: Nephrology

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $2,800