Evidence map›Paper›PMID 42539492›Full record

ArticleFrontiers in nephrology2026

Spatial transcriptomic analysis of kidney biopsies identifies activation of complement and SPP1 networks in

Spyros Karaiskos, Luis Santana-Quintero, Cherri Bott, Rahul Paul, Sergey V Brodsky, Isabelle Ayoub, Samir V Parikh, Brad H Rovin, Tibor Nadasdy, Hira L Nakhasi and 2 more

Abstract read
In one paragraph

Article in Frontiers in nephrology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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0citing papers in PubMed
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1 · What the graph read from it

What it found

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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

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Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

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5 · Who and what money

Authors and funding

12 authors.

Spyros KaraiskosDivision of Analytics & Benefit-Risk Assessment, Office of Biostatistics and Phramacovigilance Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, MD, United States.
Luis Santana-QuinteroDivision of Analytics & Benefit-Risk Assessment, Office of Biostatistics and Phramacovigilance Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, MD, United States.
Cherri BottDepartment of Pathology, Renal and Transplant Pathology Division, The Ohio State University, Columbus, OH, United States.
Rahul PaulDivision of Analytics & Benefit-Risk Assessment, Office of Biostatistics and Phramacovigilance Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, MD, United States.
Sergey V BrodskyDepartment of Pathology, Renal and Transplant Pathology Division, The Ohio State University, Columbus, OH, United States.
Isabelle AyoubDepartment of Internal Medicine, Nephrology Division, The Ohio State University, Columbus, OH, United States.
Samir V ParikhDepartment of Internal Medicine, Nephrology Division, The Ohio State University, Columbus, OH, United States.
Brad H RovinDepartment of Internal Medicine, Nephrology Division, The Ohio State University, Columbus, OH, United States.
Tibor NadasdyDepartment of Pathology, Renal and Transplant Pathology Division, The Ohio State University, Columbus, OH, United States.
Hira L NakhasiDivision of Emerging and Transfusion Transmitted Diseases, Office of Blood Research and Review Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, MD, United States.
Sreenivas GannavaramDivision of Emerging and Transfusion Transmitted Diseases, Office of Blood Research and Review Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, MD, United States.
Anjali A SatoskarDepartment of Pathology, Renal and Transplant Pathology Division, The Ohio State University, Columbus, OH, United States.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Background: Methods: To dissect the complex underlying immunopathology, we analyzed formalin-fixed paraffin-embedded kidney biopsy tissues from three patients with SAGN and one normal control kidney (NCK) using single-cell spatial transcriptomics (analyzing a total of 3,993 cell-specific transcriptomes). The SAGN biopsies showed diffuse endocapillary hypercellularity with focal crescents. Following annotation of various cell types, we constructed cell communication networks using CellChat to identify ligand-receptor interactions in normal and SAGN kidneys. Results: Secreted phosphoprotein 1 (SPP1/osteopontin) emerged as the most enriched signaling network in SAGN with markedly increased autocrine and paracrine SPP1-CD44 activity among tubular segments and parietal epithelial cells (PECs). In contrast, SPP1-integrin signaling was mainly observed in healthy control kidneys. Consistent with previous reports, complement pathway activation was detected exclusively in diseased kidneys, with PECs as principal signal receivers, suggesting the potential role in crescent formation. Transcripts for C2, C3, CD55, Factor B, and Factor D showed significant upregulation in SAGN. In contrast, vascular endothelial growth factor (VEGF), angiopoietin-like proteins (ANG PTL), and progranulin/granulin networks exhibited decreased communication probabilities in SAGN versus NCK, suggesting the suppression of protective angiogenic and anti-inflammatory signaling. Immunofluorescence staining for SPP1 showed increased staining in renal tubular segments in SAGN biopsies, supporting our transcriptomic data. Conclusion: SPP1 and complement pathways appear to drive pro-inflammatory responses, while protective VEGF signaling is compromised, providing potential therapeutic targets for this disease.

Indexed as

Angiopoietin like proteins (ANG PTL)Integrin alpha X (ITGAX)Parietal epithelial cells (PECs), complementPlacental growth factor (PGF)protease activated receptors (PARs)Secreted phosphoprotein 1 (SPP1)vascular endothelial growth factor (VEGF)

Identifiers

PMID42539492
PMCPMC13423683

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.