Kidney Week 2025 Annual Meeting-Controversies in Glomerular Disease Therapeutics

Video Transcription

Video Summary

The session on controversies in glomerular disease therapeutics highlighted how emerging targeted treatments require clearer mechanistic thinking beyond traditional histologic labels.<br /><br />Dr. Marina Vivarelli reviewed evidence that complement activation contributes not only to glomerular injury but also to tubulointerstitial damage and fibrosis. Tubular epithelial cells can produce complement (notably C3), amplifying inflammation and promoting epithelial-to-mesenchymal transition and scarring. In diabetic kidney disease, animal studies suggest benefit from blocking the terminal pathway (C5a/C5aR), and recent human urine proteomics identified “high complement” signatures that predict rapid progression. Complement also appears relevant in ischemia-reperfusion injury after transplantation (especially lectin pathway components), though delivery to ischemic tubules is challenging and trials have been mixed. Preclinical data in proteinuric models (MCD/FSGS) implicate lectin and terminal pathways, and microdissection/proteomics suggest tubular alternative pathway activation across immune glomerulopathies.<br /><br />Dr. Heather Reich presented work in IgA nephropathy challenging the assumption that pathogenic IgA is produced only in mucosal tissues. Using BAFF-transgenic mouse models, Neisseria-focused experiments, ELISPOT, flow cytometry, single-cell and spatial transcriptomics, her group identified IgA-producing plasma cells within kidneys, including near glomeruli, evolving from proliferative to long-lived phenotypes—raising the possibility that BAFF/APRIL-directed therapies could act on intrarenal plasma cell niches.<br /><br />Dr. Salim Almaani discussed “how much immunomodulation is too much,” emphasizing infections and cardiovascular risk, strongly linked to corticosteroid dose and duration. Evidence from IgA, lupus, and ANCA vasculitis supports steroid minimization strategies (TESTING, PEXIVAS) and newer approaches (avacopan), plus attention to patient risk factors (diabetes, low IgG), prophylaxis, and future precision tools (TTV monitoring, antigen-specific CAR approaches, tolerogenic vaccines).<br /><br />Dr. Hans-Joachim Anders argued that managing glomerular diseases often requires treating both immune activity and CKD progression mechanisms (RAS blockade, SGLT2 inhibitors, finerenone, diet), with priorities varying by chronic, relapsing, or rapidly progressive presentations, and stressed early detection to maximize long-term dialysis-free survival.

Asset Subtitle

Moderator(s): Tingting Li, Ladan Zand

Presentation(s):

Is There a Role for Complement Inhibition Outside of the Glomerulus? - Marina Vivarelli
Could B Cell-Directed Therapies Have a Direct Action Within the Kidneys? - Heather Reich
How Much Immune and Inflammatory Modulation Is Too Much? - Salem Almaani
Treating Immunology vs. CKD: Do We Always Need Both to Manage Glomerular Diseases? - Hans Anders

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

Meta Tag

Date 11/9/2025

Pathway 1 Glomerular Diseases

Pathway 2 Pediatric Nephrology

Session ID 507302

Keywords

glomerular disease therapeutics

targeted treatments

complement activation

tubulointerstitial damage

renal fibrosis

tubular epithelial C3

epithelial-to-mesenchymal transition

diabetic kidney disease

C5a/C5aR blockade

urine proteomics high-complement signature

ischemia-reperfusion injury transplantation

lectin pathway complement

IgA nephropathy intrarenal plasma cells

BAFF/APRIL-directed therapy

steroid minimization strategies