Kidney Week

Abstract: TH-PO0315

Spatial Transcriptomics Reveals Glomerular Molecular Boundary Associated with Treatment Response in Patients with FSGS

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

• Takeuchi, Miyoshi, Kyushu Daigaku, Fukuoka, Fukuoka Prefecture, Japan

Miyoshi Takeuchi, MD

• Hayashi, Sahomi, Kyushu Daigaku, Fukuoka, Fukuoka Prefecture, Japan

Sahomi Hayashi, MD, PhD

• Setoyama, Daiki, Hokkaido Daigaku, Sapporo, Hokkaido Prefecture, Japan

Daiki Setoyama, PhD

• Iwamoto, Takaki, Kyushu Daigaku, Fukuoka, Fukuoka Prefecture, Japan

Takaki Iwamoto, MD

• Kishimoto, Hiroshi, Kyushu Daigaku, Fukuoka, Fukuoka Prefecture, Japan

Hiroshi Kishimoto, MD

• Tsuchimoto, Akihiro, Kyushu Daigaku, Fukuoka, Fukuoka Prefecture, Japan

Akihiro Tsuchimoto, MD, PhD

• Yamada, Shunsuke, Kyushu Daigaku, Fukuoka, Fukuoka Prefecture, Japan

Shunsuke Yamada, MD, DrMed, PhD, DrPH

• Ago, Tetsuro, Kyushu Daigaku, Fukuoka, Fukuoka Prefecture, Japan

Tetsuro Ago, MD, PhD

• Kunisaki, Yuya, Kyushu Daigaku, Fukuoka, Fukuoka Prefecture, Japan

Yuya Kunisaki, MD, PhD

• Nakano, Toshiaki, Kyushu Daigaku, Fukuoka, Fukuoka Prefecture, Japan

Toshiaki Nakano, MD, PhD

Background

Focal segmental glomerulosclerosis (FSGS) is histologically characterized by focal and segmental sclerosis. Molecular events preceding pathologically diagnosed sclerosis in glomerular cells are not fully understood.

Methods

We performed spatial transcriptome analysis of kidney biopsy paraffin sections from 16 FSGS patients, with those from 6 healthy controls, and 4 IgA nephropathy (IgAN) and 3 minimal change disease. We classified the glomeruli into four categories (Cluster 1 [C1], Cluster 0 [C0], Cluster 2 [C2], and Cluster 3 [C3]) as "glomerular molecular states" based on gene expression patterns.

Results

Healthy controls were predominantly composed of the C1 glomeruli, whereas the FSGS kidneys showed increased proportions of C0, C2, and C3 glomeruli. IgAN was characterized by a high proportion of the C2 glomeruli, representing an immune-enriched molecular state. In the FSGS specimens, proportions of the C0 glomeruli showed a positive correlation with baseline eGFR, whereas the C3 glomeruli showed a negative correlation. Across multiple analyses, including Hallmark pathway analysis, a continuous alteration in the order C1, C0, C2 and C3 was observed, with predominant pathways shifted from inflammatory signaling in the early states (C1 and C0) to extracellular matrix pathways in the advanced states (C2 and C3). Intercellular interaction analysis showed a transition from endothelin signaling towards platelet-derived growth factor and collagen signaling. These changes suggested a molecular boundary between C0 and C2, accompanied by a shift from an inflammatory-dominant phase to a structural remodeling phase during disease progression. Fibroblasts and immune cells in the periglomerular region gradually increased, peaking at C2 and remaining elevated thereafter. Furthermore, the proportion of glomeruli classified into the early states was a significant and independent predictor of post-treatment proteinuria compared to conventional pathological classification (Columbia classification) and baseline eGFR. We identified Nicotinamide N-Methyltransferase and Complement C1q Subcomponent Subunit C as representative markers associated with the inflammatory and remodeling phases.

Conclusion

These results provide a new perspective on FSGS pathogenesis by capturing molecular alterations that precede overt sclerotic changes.

Funding

• Government Support – Non-U.S.