Membranous Nephropathy - PLA2R Induced

Objective: To assess the disappearance rate (half-life) of anti-PLA2R antibodies in high-risk primary membranous nephropathy (pMN) patients treated with obinutuzumab (OBI), and to evaluate immunological and clinical remission, adverse events, and quality of life. Design: Open-label, single-center, prospective pilot intervention study conducted at Radboud University Medical Center. Population: 20 adult patients with high-risk PMN, defined by proteinuria ≥3.5 g/24h despite 6 months of supportive treatment with ACE inhibitors or ARBs. Intervention: OBI 1000 mg on days 1 and 15, with two additional infusions after 6 months if anti-PLA2R antibody levels remain positive and proteinuria exceeds 2 g/24h. Follow-up: Patients were monitored at baseline, and at weeks 1, 2, 4, 8, 12, 24, 37, and 52.

This study is a single-center, open-label, dose-escalation exploratory clinical trial, expected to enroll 6 to 12 participants. It will use a BOIN (Bayesian Optimal Interval) design for dose escalation, with four predetermined dose groups (0.3×10\^6 cells/kg, 1.0×10\^6 cells/kg, 3.0×10\^6 cells/kg, and an alternative dose of 0.1×10\^6 cells/kg). Each dose group plans to enroll 1-2 or 3-6 participants with relapsed or refractory autoimmune-mediated kidney diseases (such as lupus nephritis, ANCA-associated vasculitis, membranous nephropathy, and IgG4-related diseases).