Kidney Week 2025 Annual Meeting-Pathology: Novel Mechanisms and Modalities

Video Transcription

Video Summary

This recorded ASN oral abstract session on “Pathology: Novel Mechanisms and Modalities” featured multiple talks highlighting new assays, mechanistic insights, and technologies in kidney disease.<br /><br />Dr. Laith Alrabadi presented development of quantitative immunoassays for anti-HTRA1, a target antigen in a minority of membranous nephropathy (MN) cases. Because Western blot is semi-quantitative, his team optimized ELISA (tag choice, expression system, active vs inactive HTRA1) and showed antibody levels—especially IgG4—correlate with proteinuria, fall after rituximab before clinical remission, and rise before relapse. Borderline cases were clarified using capillary “Western” electrophoresis, an automated, low-volume, more quantitative approach.<br /><br />Dr. Aaron Story (Arkana) described a clinical mass spectrometry assay to type MN antigens by immunopurifying immune complexes from residual frozen biopsy tissue, spiking internal standards, and quantifying antigen peptides via targeted MS. Using immunostaining as ground truth, the workflow achieved ~97% sensitivity and 100% specificity in validation, detected occasional dual-antigen cases, and provided ~54% typing yield in PLA2R-negative MN, with plans to expand the antigen panel.<br /><br />Dr. Sarah Tortenez (Paris) profiled acute interstitial nephritis etiologies using multiplex immunofluorescence and RNA-seq, finding distinct cellular infiltrates: drug-induced (more CD8 T cells/plasma cells), sarcoidosis (M1 macrophages, CD4 T cells, Tregs; IFN-γ/TNF-α signature), TINU (more M2 macrophages/B cells), and infection (neutrophils, CD4 T cells).<br /><br />Other presentations covered multiplexed protein imaging of tubular casts identifying UMOD, IGF-BP7, and PROM1 (a potential urinary biomarker) and associated tubular injury; smartphone macro-photography to assess kidney biopsy adequacy with high agreement versus microscopy (κ≈0.95); KPMP data linking tubular injury in CKD to maladaptive proximal tubule states and biomarkers (KIM-1, IL-18); podocyte PAI-1 knockdown protecting against injury via cytoskeletal/RhoA pathways; podocyte-derived fibulin-1 acting as a novel EGFR ligand driving mesangial activation and glomerulosclerosis; and a human kidney organoid model of AL amyloidosis showing kappa fibril deposition and podocytopathy for therapeutic testing.

Asset Subtitle

Moderator(s): Nicole Andeen, Jonathan Zuckerman

Presentation(s):

Novel Quantitative Immunoassays for Anti-HTRA1 Antibodies in Membranous Nephropathy - Laith Al-Rabadi
Multiplexed Detection of Membranous Antigens by Mass Spectrometry - Aaron Storey
Phenotypic and Molecular Signatures in Acute Interstitial Nephritis - Sarah Tortonese
Redefining the Composition and Significance of Human Renal Intratubular Casts Using Spatial Protein Imaging - Azuma Nanamatsu
Real-Time Kidney Biopsy Adequacy Assessment Using Built-In Smartphone Macrophotography - Minji Kim
The Issue Is Tissue: KPMP Research Biopsies Detect Severe Tubular Injury in Stable CKD - Insa Schmidt
Podocyte Cytoskeletal Stabilization Through RhoA-Cofilin Signaling by Suppressing PAI-1 - Jianyong Zhong
Fibrillin-1 Is a Novel Ligand of Epidermal Growth Factor (EGF) Receptor That Promotes Mesangial Cell Activation and Glomerulosclerosis - He Zhi
Kidney Organoid Model of Light Chain Amyloidosis - Humayra Afrin

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

Meta Tag

Date 11/7/2025

Pathway 1 Pathology

Session ID 519894

Keywords

ASN oral abstract session

kidney pathology novel mechanisms

membranous nephropathy HTRA1

anti-HTRA1 ELISA immunoassay

IgG4 antibody levels proteinuria

rituximab response relapse biomarker

capillary electrophoresis automated western

mass spectrometry antigen typing MN

PLA2R-negative membranous nephropathy

acute interstitial nephritis multiplex immunofluorescence RNA-seq

tubular injury biomarkers KIM-1 IL-18

podocyte PAI-1 RhoA cytoskeleton protection

kidney organoid AL amyloidosis kappa fibrils