Kidney Week

Abstract: TH-PO0341

Computationally Derived Tubular Morphometric Signatures Define Transcriptionally Distinct States of Tubular Injury in FSGS/Minimal Change Disease (MCD)

Session Information

• Glomerular Diseases: Omics
  October 22, 2026 | Location: Exhibit Hall A, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Glomerular Diseases

• 1401 Glomerular Diseases: Mechanisms, including Podocyte Biology

Authors

• Nair, Viji, University of Michigan Michigan Medicine, Ann Arbor, Michigan, United States

Viji Nair, PhD

• Smith, Cathy, University of Michigan Michigan Medicine, Ann Arbor, Michigan, United States

Cathy Smith, PhD

• Fan, Fan, Emory University, Atlanta, Georgia, United States

Fan Fan, MS

• Eichinger, Felix H., University of Michigan Michigan Medicine, Ann Arbor, Michigan, United States

Felix H. Eichinger

• McCown, Phillip J., University of Michigan Michigan Medicine, Ann Arbor, Michigan, United States

Phillip J. McCown, MS, PhD

• Demeke, Dawit S., University of Michigan Michigan Medicine, Ann Arbor, Michigan, United States

Dawit S. Demeke, MD

• Alaba, Mathew Olakunle, University of Michigan Michigan Medicine, Ann Arbor, Michigan, United States

Mathew Olakunle Alaba, MS

• Wang, Bangchen, Duke University, Durham, North Carolina, United States

Bangchen Wang, MD, PhD

• Jacobs, Jackson, Duke University, Durham, North Carolina, United States

Jackson Jacobs

• Ozeki, Takaya, Nagoya Daigaku Daigakuin Igakukei Kenkyuka Igakubu, Nagoya, Aichi Prefecture, Japan

Takaya Ozeki, MD, PhD

• Liu, Qian, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, United States

Qian Liu, MPH

• Bitzer, Markus, University of Michigan Michigan Medicine, Ann Arbor, Michigan, United States

Markus Bitzer, MD

• Mariani, Laura H., University of Michigan Michigan Medicine, Ann Arbor, Michigan, United States

Laura H. Mariani, MD, MS, FASN

• Lafata, Kyle Jon, Duke University, Durham, North Carolina, United States

Kyle Jon Lafata, PhD

• Holzman, Lawrence B., The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, United States

Lawrence B. Holzman, MD

• Madabhushi, Anant, Emory University, Atlanta, Georgia, United States

Anant Madabhushi, PhD

• Zee, Jarcy, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, United States

Jarcy Zee, PhD, FASN

• Kretzler, Matthias, University of Michigan Michigan Medicine, Ann Arbor, Michigan, United States

Matthias Kretzler, MD

• Barisoni, Laura, Duke University, Durham, North Carolina, United States

Laura Barisoni, MD, FASN

• Janowczyk, Andrew, Duke University, Durham, North Carolina, United States

Andrew Janowczyk, PhD

• Hodgin, Jeffrey B., University of Michigan Michigan Medicine, Ann Arbor, Michigan, United States

Jeffrey B. Hodgin, MD, PhD

Background

Tubular pathomics-derived morphometric signatures (TMS) quantitatively capture the spectrum of tubular structural damage. However, their underlying molecular basis remains unclear. Here, we examined associations between TMS and transcriptional programs and cell states to identify molecular markers of tubular damage by integrating TMS with both spatial and bulk gene expression profiles.

Methods

Twelve TMSs were derived using machine leanring algorithm from segmented basement membranes, nuclei, epithelium, and lumen on PAS images of 288,712 tubules from 254 NEPTUNE/CureGN biopsies (135 FSGS, 119 MCD). Bulk tubulointerstitial gene expression from 147 NEPTUNE biopsies was correlated with TMS; enriched pathways were identified by Ingenuity Pathway Analysis (FDR<0.01). Cell types for 3,190 tubules were defined using Xenium (5000) spatial transcriptomics (6 FSGS biopsies) and compared against each tubule's highest scoring TMS.

Results

Seven of 12 TMSs correlated with tubulointerstitial transcriptional profiles. Pathway activation z-scores increased progressively from normal (TMS2, TMS4) through injury (TMS7, TMS8, TMS10) to atrophic states (TMS11, TMS12), including adaptive immune crosstalk (TCR, BCR, TRIM21, SLAMF signaling), Fc/phagocytic responses, damage/cytokine amplification (S100, cytokine storm), complement, and neutrophil degranulation. Spatially, the adaptive proximal tubule (aPT) dedifferentiated cell state progressively increased across the same TMS trajectory (Figure).

Conclusion

These data suggest that (a) computationally derived TMSs capture biologically meaningful tubular states associated with distinct transcriptional programs and cell identities, linking structure to function, and (b) tubular structural changes along the normal-to-atrophy trajectory reflect progressive immune-mediated injury. Together, these findings position pathomic analysis as a scalable, accessible surrogate for molecular disease characterization and establish a computational framework to inform treatment decision-making.

Spatial cell type proportions (y-axis) within TMS categories (x-axis)

Funding

• NIDDK Support