Kidney Week 2025 Annual Meeting-Expanding Therapeutic Horizons in IgAN

Video Transcription

Video Summary

The session reviews rapidly expanding treatment options for IgA nephropathy and why earlier intervention matters. Data from RADAR, Sweden, and Kaiser Permanente show that even “low-grade” proteinuria meaningfully predicts long-term GFR decline, challenging older assumptions. Speakers emphasize a shift toward using proteinuria as an FDA-accepted surrogate endpoint, enabling shorter clinical trials; this has helped drive more than 70 active trials and several recent drug approvals (e.g., targeted-release budesonide and sparsentan fully approved; complement and endothelin-pathway agents with accelerated approval; BAFF/APRIL therapies gaining momentum).<br /><br />Dr. Ali Gharavi summarizes genetic insights supporting the “four-hit” model: heritable galactose-deficient IgA1, autoantibodies, circulating immune complexes, and kidney deposition with complement activation. Genetics highlight key pathways (alternative complement, APRIL) that now align with effective targeted therapies, and reveal disease heterogeneity, including monogenic mimics (COL4/Alport-spectrum and podocyte genes) that influence prognosis and steroid responsiveness.<br /><br />Dr. Anna Malvar presents biopsy-based cases showing crescents can progress to irreversible sclerosis even without proteinuria, arguing proteinuria is a late marker and that hematuria and earlier biopsy may prevent missed disease. She reviews limits of systemic steroids (toxicity, relapse), benefits and relapse with budesonide, and strong interim proteinuria/Gd-IgA1 reductions with BAFF/APRIL inhibitors, while noting unanswered questions about timing, combination therapy, duration, and better biomarkers.

Asset Subtitle

Moderator(s): Myda Khalid

Presentation(s):

Introduction - Myda Khalid
Emerging Insights in the Diagnosis and Care of Patients with IgAN - Ali Gharavi
Targeting APRIL and BAFF: A New Frontier in IgAN Therapy - Ana Malvar

Support is provided by educational grants from Otsuka America Pharmaceutical, Inc. and Vera Therapeutics, Inc.

Meta Tag

Date 11/7/2025

Pathway 1 Glomerular Diseases

Session ID 521299

Keywords

IgA nephropathy

proteinuria surrogate endpoint

GFR decline prediction

targeted-release budesonide

sparsentan

complement pathway inhibitors

endothelin pathway agents

BAFF/APRIL inhibitors

four-hit model (Gd-IgA1 immune complexes)