Kidney Week 2025 Early Program - Glomerular Diseases: 2025 Update-Membranous Nephropathy

Video Transcription

Video Summary

Dr. Shane Bobart reviews how membranous nephropathy (MN) has shifted from a “primary vs secondary” framework to an antigen- and serology-driven, target-antigen approach. Discovery of anti-PLA2R antibodies (present in ~60% of primary MN) transformed diagnosis and monitoring: titers correlate with immunologic activity and precede clinical changes in proteinuria. Combined ELISA (≥2 RU/mL) plus positive immunofluorescence (IFA) can support a noninvasive diagnosis in selected low-risk patients with preserved GFR and no secondary causes, though biopsy is recommended with reduced GFR, atypical course, planned immunosuppression, suspected secondary disease, and especially diabetes due to false positives. THSD7A accounts for ~2–5% and is malignancy-associated, prompting enhanced cancer screening. Many newer antigens (e.g., EXT1/2, NELL1, semaphorin-3B, contactin-1) link MN to specific conditions (autoimmunity, malignancy, drugs, infections), guiding evaluation and treatment.<br /><br />Management emphasizes supportive care plus achieving immunologic remission, using KDIGO risk stratification. Rituximab became standard after MENTOR showed better sustained remissions vs cyclosporine. Very high-risk disease may require cyclophosphamide-based regimens. Emerging therapies include obinutuzumab, ofatumumab, proteasome inhibitors, anti-CD38 agents, and future antigen-specific CAR-based approaches. A discussion highlights that “complete immunologic remission” should mean undetectable PLA2R (ELISA <2) confirmed by negative IFA.

Asset Subtitle

Shane Bobart

Meta Tag

Module GLOM

Speaker Shane Bobart

Keywords

membranous nephropathy

anti-PLA2R antibodies

antigen-driven diagnosis

THSD7A malignancy association

KDIGO risk stratification

rituximab MENTOR trial

immunologic remission monitoring