Kidney Week

Abstract: SA-PO0847

Single-Nucleus Kidney Biopsy Profiling Defines Transport Reserve, Fibroinflammatory Remodeling, and Disease-Residual Molecular Patient States Across the Spectrum of Primary Glomerular Diseases

Session Information

• Glomerular Diseases: Management, Evolving Strategies, and Practice-Changing Advances
  October 24, 2026 | Location: Exhibit Hall A, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Glomerular Diseases

• 1402 Glomerular Diseases: Clinical, Outcomes, and Therapeutics

Authors

• Hong, Shaun G., Purdue University Weldon School of Biomedical Engineering, West Lafayette, Indiana, United States

Shaun G. Hong, PhD

• Kim, Donggun, Seoul National University Hospital Department of Internal Medicine, Jongno-gu, Seoul, Korea (the Republic of)

Donggun Kim

• Park, Sehoon, Seoul National University Hospital Department of Internal Medicine, Jongno-gu, Seoul, Korea (the Republic of)

Sehoon Park, MD, PhD

• Kim, Dong Ki, Seoul National University Hospital Department of Internal Medicine, Jongno-gu, Seoul, Korea (the Republic of)

Dong Ki Kim, MD, PhD

Background

Histology is indispensable, but diagnostic labels mask molecular states separating nephron reserve from lesion biology. We tested whether biopsy-scale snRNA-seq recovers this hidden structure across glomerular diseases.

Methods

We profiled 125 biopsies (889,646 nuclei; control, DKD, IgAN, MCD, MN, FSGS). Inference used >1,000-nucleus biopsies (n=115). We derived transport-preservation (T_s) and fibroinflammatory-remodeling (R_s) scores, modeled adjusted clinical associations (n=71), tested residual structure after Ts/Rs removal, and assessed reduced-gene/Xenium readouts.

Results

T_s and R_s were near-orthogonal (ρ=–0.084, P=0.372). R_s, not T_s, separated diagnoses (η²=0.143, P=0.004 vs 0.068, P=0.167). Baseline eGFR mapped to T_s after disease adjustment (β=6.48, P=0.034), while A_s=T_s–R_s did not (β=2.49, P=0.325). Proteinuria remained diagnosis-structured: MCD/MN had heavy proteinuria without DKD-like remodeling. After T_s/R_s removal, glomerular residual structure remained disease-associated (PERMANOVA η²=0.108, P=0.004, FDR=0.020). An 8-gene proxy reproduced the full axis (ρ=0.973; gene-held-out ρ=0.919); Xenium-panel surrogate remained concordant (ρ=0.944).

Conclusion

snRNA-seq recovers patient states compressed by glomerular disease labels, separating transport reserve, disease-context glomerular biology, and reduced-assay candidates for molecular pathology.

Acknowledgment

We thank participating patients and the KORNERSTONE/SNUH teams.

Funding

• Government Support – Non-U.S.