Kidney Week

Abstract: TH-PO0319

Intrarenal Activation of Complement and SPP1 Pathways in Staphylococcus Infection-Associated Glomerulonephritis (SAGN): A Single-Cell Spatial Transcriptomic Study

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

• Gannavaram, Sreenivas, Center for Biologics Evaluation and Research, Rockville, Maryland, United States

Sreenivas Gannavaram, PhD

• Bott, Cherri N., The Ohio State University Wexner Medical Center, Columbus, Ohio, United States

Cherri N. Bott

• Brodsky, Sergey V., The Ohio State University Wexner Medical Center, Columbus, Ohio, United States

Sergey V. Brodsky, MD, PhD

• Ayoub, Isabelle, The Ohio State University Wexner Medical Center, Columbus, Ohio, United States

Isabelle Ayoub, MD, MPH, FASN

• Parikh, Samir V., The Ohio State University Wexner Medical Center, Columbus, Ohio, United States

Samir V. Parikh, MD, FASN

• Nadasdy, Tibor, The Ohio State University Wexner Medical Center, Columbus, Ohio, United States

Tibor Nadasdy, MD

• Satoskar, Anjali A., The Ohio State University Wexner Medical Center, Columbus, Ohio, United States

Anjali A. Satoskar, MD

Background

SAGN has emerged as the leading cause of infection-related glomerulonephritis (IRGN) in the Western subcontinents, but pathogenesis remains poorly understood in the absence of animal models and detailed molecular mechanisms.

Methods

We analyzed formalin-fixed paraffin-embedded kidney biopsy tissues from three SAGN patients and one normal control kidney (NCK) using single-cell spatial transcriptomics (analyzing a total of 3,993 cell-specific transcriptomes). Following annotation of various cell types, we constructed cell communication networks using CellChat to identify ligand-receptor interactions in SAGN and normal control kidneys (NCK).

Results

Secreted Phosphoprotein 1 (SPP1/osteopontin) emerged as the most enriched network in SAGN (Fig. 1) with markedly increased SPP1-CD44 signaling activity among multiple tubular segments. Complement pathway activation was detected exclusively in SAGN kidneys (not in normal control). Parietal epithelial cells (PECs) were the principal signal receivers in both these networks. Vascular endothelial growth factor (VEGF), angiopoietin-like proteins (ANGPTL) and Progranulin/Granulin networks exhibited decreased communication probabilities in SAGN. Transcripts for C2, C3, CD55, Factor B, Factor D, and placental growth factor (PGF) showed significant upregulation in SAGN.

Conclusion

SPP1 and complement pathways appear to drive pro-inflammatory responses with possible contribution from downregulated Progranulin/Granulin network. The VEGF signaling is compromised, suggesting suppression of protective angiogenic and anti-inflammatory signaling in SAGN.

Acknowledgment

Spyros Karaiskos, Luis Santana-Quintero, Rahul Paul - Bioinformatics support
Part of the work done at FDA. Our contributions are an informal communication and represent our own best judgement. These comments do not bind or obligate FDA.

Enriched communication nodes in SAGN versus normal control kidney

Upregulated complement transcripts in SAGN

Funding

• Clinical Revenue Support