Kidney Week 2025 Annual Meeting-Membranous Nephropathy: From Science to Personalized Patient Care

Video Transcription

Video Summary

The session opened with a tribute to Dr. William G. Couser, highlighting his foundational work in membranous nephropathy (MN) and glomerular immunology. Dr. David Salant described Couser’s leadership, global mentorship, and a landmark 1978 study showing that MN deposits form from antibodies binding intrinsic podocyte antigens—not trapped circulating immune complexes—establishing the modern pathogenic paradigm.<br /><br />Subsequent talks focused on how antigen and antibody discoveries are reshaping diagnosis, prognosis, and therapy. Dr. Hoxha summarized MN as an antigen-defined autoimmune disease, most commonly driven by anti-PLA2R antibodies, which guide diagnosis and treatment monitoring. He emphasized heterogeneity across antigens (e.g., NELL1, THSD7A, EXT1/2) and presented emerging evidence that some patients may have dual antigens/antibodies, with uncertain mechanisms and potential prognostic implications. He also discussed animal models proving PLA2R antibody pathogenicity (minipig and transgenic mouse), residual immunologic activity despite “negative” ELISA, and early work toward antigen-specific therapies (e.g., monoclonal antibodies mapping PLA2R epitopes, CAR-based approaches).<br /><br />Dr. Tiffany Caza addressed when kidney biopsy remains necessary. While PLA2R serology can allow noninvasive diagnosis in typical cases, biopsy is important with reduced GFR, comorbidities (e.g., diabetes), negative serology, treatment resistance, or suspected secondary causes. Biopsy and mass spectrometry can identify specific antigens linked to actionable triggers (malignancy, autoimmune disease, drugs, infections like syphilis, transplant-related disease) and can detect dual-antigen MN.<br /><br />Dr. Larry Beck reviewed how serial PLA2R titers, often alongside serum albumin, can guide starting, adjusting, shortening, or extending immunosuppression, predict relapse, and distinguish immunologic activity from persistent structural proteinuria.<br /><br />Professor Pierre Ronco reviewed future therapies, particularly complement inhibition and more potent B-cell/plasma-cell targeting. Complement is clearly activated in MN (despite IgG4 dominance), but complement-inhibitor trials have largely failed so far, possibly due to pharmacokinetics, pathway heterogeneity, and target selection. Promising directions include next-generation anti-CD20 (obinutuzumab), anti-CD38 plasma-cell therapies, combination strategies, and antigen-specific CAR T/NK cell approaches.

Asset Subtitle

Moderator(s): Dhruti Chen, Patrick Nachman

Presentation(s):

Pathogenesis of Membranous Nephropathy: Underlying Science and Its Impact on Patient Care - Elion Hoxha
Noninvasive or Invasive Diagnosis? Why We Still Need Kidney Biopsies in Membranous Nephropathy - Tiffany Caza
Management of Membranous Nephropathy: Biomarkers and a Personalized Medicine Approach to Therapy - Laurence Beck
Membranous Nephropathy: New Treatments on the Horizon - Pierre Ronco

Support for all sessions in the Glomerular Diseases Learning Pathway is provided by an educational grant from Vera Therapeutics, Inc.

Meta Tag

Date 11/8/2025

Pathway 1 Glomerular Diseases

Session ID 504281

Keywords

Dr. William G. Couser

membranous nephropathy

glomerular immunology

podocyte antigens

anti-PLA2R antibodies

antigen-defined autoimmune disease

NELL1

THSD7A

EXT1/EXT2

dual-antigen membranous nephropathy

kidney biopsy indications

PLA2R titer monitoring

complement inhibition therapies