Kidney Week Educational Symposia-Expanding Therapeutic Landscape in Lupus Nephritis: Utilization of B Cell Targeted Therapy

Video Transcription

Video Summary

The session focuses on lupus nephritis (LN) pathogenesis and treatment, emphasizing B-cell–driven immunity and preventing flares to avoid irreversible kidney damage and chronic kidney disease (CKD) complications. Dr. Anders reframes LN as a “standard” autoimmune disease: repeated nephritis episodes progressively reduce nephron reserve, making remission harder and accelerating long-term cardiovascular and kidney failure risks. Management must address both immune activity and CKD care, guided by biopsy activity versus chronicity indices. He simplifies pathogenesis to persistent immune memory in three autoreactive “clones”: B cells (lymph nodes/spleen), T cells, and plasma cells (bone marrow). Because lupus involves many autoantigens (many clones), rituximab often underperforms compared with single-antigen diseases; deeper B-cell targeting (e.g., CD19 approaches, possibly CAR-T) supports B cells as a central therapeutic target. Interferon likely contributes to initiation, but its renal role awaits clearer trial evidence.<br /><br />Dr. Kastor reviews B-cell therapies in LN: early anti-CD20 trials (LUNAR, BELONG) were negative or had infection concerns, while BLISS-LN showed belimumab improved 2-year renal outcomes and reduced renal events/flares. Obinutuzumab (NOBILITY) produced higher remission rates with sustained B-cell depletion and acceptable safety; the phase 3 REGENCY trial reportedly met its primary endpoint (data pending). CAR-T (anti-CD19) case series in refractory SLE (including LN history) showed marked, durable proteinuria improvements but requires caution due to complexity and safety (e.g., cytokine release syndrome). Discussion highlights personalization limits, the importance of adherence (favoring IV options), and uncertainty about combining plasma-cell and B-cell therapies.

Asset Subtitle

Moderator(s): Isabelle Ayoub

Presentation(s):

Introduction - Isabelle Ayoub
Pathogenesis of Lupus Nephritis: Focus on B Cell Tolerance - Hans Anders
Treatment of Lupus Nephritis: Focus on B Cell Targeting Therapies - Dawn Caster

Support is provided by an educational grant from Genentech, a member of the Roche Group.

Meta Tag

Date 10/25/2024

Pathway 1 Glomerular Diseases

Session ID 495599

Session Type ES - Educational Symposium

Keywords

lupus nephritis

pathogenesis

B-cell–driven immunity

chronic kidney disease (CKD)

renal biopsy activity and chronicity indices

B-cell targeted therapy

belimumab (BLISS-LN)

obinutuzumab (NOBILITY/REGENCY)

anti-CD19 CAR-T therapy