Kidney Week 2025 Annual Meeting-Decoding AKI: The Omics Revolution

Video Transcription

Video Summary

The session focused on “omics” approaches to understand acute kidney injury (AKI), its repair versus maladaptive progression to chronic kidney disease (CKD), and related injury contexts.<br /><br />Chou-Hsuan Nguyen (WashU) presented a multiscale spatial transcriptomics framework to study AKI→CKD transition in a mouse ischemia-reperfusion model. Using Xenium (subcellular, targeted ~300 genes) plus Visium (whole transcriptome, lower resolution) on adjacent sections, the team annotated ~1.3M cells across timepoints, defined proximal tubule (PT) injury states (including failed-repair VCAM1/C3-high PT), and modeled PT fate transitions across experimental time using optimal transport. They identified a branching point where injured PT cells either recover (metabolic/regenerative programs) or progress to maladaptive failed-repair states (e.g., SERPINE1, CD44). Neighborhood and permutation-based interaction analyses revealed a fibrotic-inflammatory niche with strong failed-repair PT–immune–fibroblast connectivity. Ligand–receptor inference highlighted PDGF signaling to fibroblasts and integrin/ICAM/VCAM-mediated immune tethering; findings were supported by imaging and cross-species signatures in human CKD datasets.<br /><br />Takashi Hato (Indiana) described an unpublished MRSA bacteremia mouse model where kidney infection initiates in the inner medulla (immune-privileged due to hypertonicity/acidity/hypoxia), then spreads cortically, provoking neutrophil-rich abscesses and collateral tubular necrosis, culminating in fibrosis (AKI→CKD). Lowering medullary osmolality with furosemide enabled neutrophil access to medullary clusters, accelerated bacterial clearance, and improved function. He also discussed dual-species RNA-seq/spatial approaches and MRSA adaptation via host polyamines and the SPG gene.<br /><br />Anna Favre (Geneva) used a podocyte-specific apoptosis model of pure glomerular proteinuria with single-nucleus RNA-seq plus intravital imaging. Proteinuria caused major PT remodeling, notably loss of normal S2 identity and emergence of S1/S2 “hybrid” tubules co-expressing protein-uptake and organic anion transport features, preceding injury/failed-repair trajectories. Distal convoluted tubule populations also dedifferentiated (NCAM1+), suggesting distal responses specific to proteinuric stress.<br /><br />Inza Marie Schmidt (Boston University) reviewed clinical AKI proteomics platforms and applications: biomarker discovery (e.g., urinary CXCL9 for acute interstitial nephritis), AKI subphenotyping, and pathology-linked biomarkers. She highlighted plasma proteomic markers associated with biopsy-scored acute tubular injury (e.g., osteopontin/SPP1, MRC1, tenascin C), replication across cohorts, and future directions including spatial/single-cell proteomics (e.g., PathoPlex) and multi-omic integration.

Asset Subtitle

Moderator(s): James Odum, Jennifer Schaub

Presentation(s):

AKI to CKD Transition Viewed Through the Spatial Lens - Qiao Xuanyuan
Host-Microbial Interplay in the Kidneys - Takashi Hato
Spatiotemporal Landscape of the Tubule in Response to Glomerular Proteinuria - Anna Faivre
Proteomic Landscape of Injured Kidneys - Insa Schmidt

Meta Tag

Date 11/8/2025

Pathway 1 AKI and Critical Care

Pathway 2 Kidney Biology and Physiology

Session ID 507032

Keywords

acute kidney injury

AKI to CKD transition

maladaptive repair

spatial transcriptomics

Xenium

Visium

proximal tubule injury states

failed-repair proximal tubule

optimal transport modeling

fibrotic-inflammatory niche

ligand-receptor inference

PDGF signaling

MRSA bacteremia kidney infection

proteinuria-induced tubular remodeling

clinical AKI proteomics biomarkers