Kidney Week 2025 Annual Meeting-Glomerular Precision Nephrology: Novel Mechanisms, Biomarkers, and Therapeutic Targets

Video Transcription

Video Summary

This oral abstract session on “Glomerular Precision Nephrology” featured multiple talks spanning single-cell/spatial omics, podocyte biology, therapeutic targets, biomarkers, and computational pathology.<br /><br />Saritas presented single-cell RNA/ATAC and spatial transcriptomics from 144 human kidney samples across etiologies, identifying a shared multicellular program associated with low eGFR and fibrosis/IFTA. Adaptive proximal tubule cells and immune cells drove spatially constrained inflammatory/fibrotic niches with NF-κB signaling; RELA disruption in proximal tubule cells reversed the maladaptive program, suggesting causality.<br /><br />Shibata reported that podocyte polarity factor PARD6B is downregulated in FSGS glomeruli and injury models. Podocyte-specific PARD6B knockout mice developed proteinuria and FSGS-like lesions with nephrin mislocalization/internalization, reduced integrin β1 protein, and podocyte loss/detachment, implicating polarity pathways in irreversible injury.<br /><br />Suzuki used an experimental autoimmune nephrotic syndrome model (anti-CRB2 antibodies) showing nephrin redistribution to cytosol, reduced surface nephrin, and increased Rab5/Rab7/LC3 co-localization consistent with enhanced endocytosis, amphisome/lysosomal degradation; similar nephrin changes appeared in CRB2-antibody–positive patients.<br /><br />Texera described an antibody targeting “exposed” pathological claudin-1 (sparing tight junction claudin-1). Claudin-1/CD44-positive activated parietal epithelial cells correlated with proteinuria and lower eGFR in FSGS; antibody treatment reduced albuminuria, activated PECs, and macrophage (CD68) infiltration in a secondary FSGS model.<br /><br />Estrada introduced EHD3 as a largely glomerular endothelial cell–specific promoter and generated an EHD3-rtTA mouse enabling more selective genetic manipulation of glomerular endothelium (validated via KLF4 knockdown).<br /><br />Nirenberg presented a plasma 4-protein kidney damage index (MIOX, UMOD, ARL1, HPSE) that outperformed conventional markers for early diabetic kidney disease and showed strong discrimination for lupus nephritis.<br /><br />Kemet reported from the sanctuary Phase II IgA nephropathy trial that C5 inhibition with ravulizumab rapidly reduced urinary complement activation markers (C5b-9, factor Ba), followed by decreased urinary CD163 and KIM-1; placebo crossover replicated effects.<br /><br />Fan Fan integrated tubule “pathomic” signatures with spatial transcriptomics in MCD/FSGS, deriving continuous morphometric trajectories and risk stratification linked to clinical outcomes and fibrosis/injury gene programs.<br /><br />Svacov showed preeclampsia serum induces a senescence-like phenotype in human podocytes (β-gal, p16, SASP cytokines), increased podocyte EV injury markers, reduced VEGF secretion, and impaired migration, proposing senescence as a mechanism of podocyte injury in preeclampsia.

Asset Subtitle

Moderator(s): Eunsil Hahm, Kristin Meliambro

Presentation(s):

Single-Cell Multiomics Analysis of Human Kidney Diseases - Turgay Saritas
Downregulation of PARD6B Is Associated with Irreversible Podocyte Damage in FSGS - Katsuaki Shibata
Nephrin Trafficking in the Mouse Model of Experimental Autoimmune Nephrotic Syndrome - Soichiro Suzuki
Targeting of CLDN1 Reduces Kidney Injury and Macrophage Infiltration in FSGS - Geoffrey Teixeira
A Novel Tool to Study Glomerular Endothelial Cell Biology - Chelsea Estrada
Kidney-Specific Four-Protein Index Outperforms Conventional Measures for Detecting Early Kidney Damage in Lupus Nephritis and Diabetic Kidney Disease - Mike Nerenberg
Change in Soluble Biomarker Levels in Patients with IgAN: Analysis of the Phase 2 Trial of Ravulizumab (SANCTUARY) - Tobin Cammett
Integration of Pathomic Signatures and Spatial Transcriptomics Reveals Tubular Morphometric Trajectories and Enables Patient Stratification in Minimal Change Disease (MCD)/FSGS - Fan Fan
Senescence as an Underlying Mechanism of Podocyte Injury in Preeclampsia - Sonja Suvakov

Note: Continuing education credits are not being offered for this session.

Meta Tag

Date 11/6/2025

Pathway 1 Glomerular Diseases

Session ID 519868

Keywords

Glomerular precision nephrology

single-cell RNA-seq

spatial transcriptomics

kidney fibrosis IFTA

NF-kappaB RELA signaling

adaptive proximal tubule cells

podocyte polarity PARD6B

FSGS nephrin mislocalization

CRB2 autoantibodies

claudin-1 CD44 parietal epithelial cells

EHD3-rtTA glomerular endothelium

plasma 4-protein kidney damage index

ravulizumab C5 inhibition IgA nephropathy