Abstract: FR-PO0158
Immune Drivers of Tubular Injury States in Acute Interstitial Nephritis and Acute Tubular Injury
Session Information
- AKI: Mechanisms - 2
November 07, 2025 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Acute Kidney Injury
- 103 AKI: Mechanisms
Authors
- Baker, Megan Leila, Yale School of Medicine, New Haven, Connecticut, United States
- Budiman, Tifanny, Yale School of Medicine, New Haven, Connecticut, United States
- Weiss, Marlene, Charite - Universitatsmedizin Berlin, Berlin, BE, Germany
- Kakade, Vijayakumar R., Yale School of Medicine, New Haven, Connecticut, United States
- Moledina, Dennis G., Yale School of Medicine, New Haven, Connecticut, United States
- Cantley, Lloyd G., Yale School of Medicine, New Haven, Connecticut, United States
Background
Accumulating evidence has demonstrated that immune cell responses following acute kidney injury (AKI) fundamentally shape both immediate and long-term clinical outcomes. Acute interstitial nephritis (AIN) and acute tubular injury (ATI) both involve tubular damage, with immune cells seen as the primary cause of injury in AIN versus reactive to injury in ATI.
Methods
To better understand the impact of these interactions on tubular cell outcomes, we analyzed kidney biopsies from AIN, ATI, and healthy tissues using imaging mass cytometry (n=65, external validation cohort n=41) and Xenium spatial transcriptomics (n=20) to characterize interstitial microenvironments surrounding tubular cells with differential injury marker expression.
Results
Integrative analyses revealed distinct tubular-immune interactions in AIN versus ATI. The interstitial niche surrounding "early injury" KIM-1+ proximal tubule cells showed increased CD206+ macrophages in ATI but increased dendritic cells and CD206- macrophages in AIN. Conversely, "failed repair" VCAM-1+ PTECs exhibited peritubular niches enriched with various T cell subsets in AIN, while in ATI showed only modest CD206+ macrophage increases. VCAM-1+ PTECs had increased mast cell neighbors in both AIN and ATI. Xenium analysis has allowed us to extend these findings to define the subsets of these immune cells in each niche, and define molecular pathways of communication between differentially injured tubular cells and their immune neighbors.
Conclusion
To the best of our knowledge, this is the first study to date to quantitatively analyze kidney tissue cell populations in patients with acute interstitial nephritis with single cell and spatial resolution.
Funding
- NIDDK Support