Kidney Week

Abstract: SA-PO0725

Urinary Tenascin C Predicts Kidney Function Loss in Lupus Nephritis

Session Information

• Glomerular Diseases: Profiling Through Multiomics
  November 08, 2025 | Location: Exhibit Hall, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Glomerular Diseases

• 1401 Glomerular Diseases: Mechanisms, including Podocyte Biology

Authors

• Fava, Andrea, Johns Hopkins Medicine Division of Rheumatology, Baltimore, Maryland, United States

Andrea Fava, MD

• Lee, Chen-Yu, Johns Hopkins Medicine Division of Rheumatology, Baltimore, Maryland, United States

Chen-Yu Lee, MD, MS

• Taghavi, Sepehr, Exagen Inc, Vista, California, United States

Sepehr Taghavi, MS

• Zhang, Shangzhu, Johns Hopkins Medicine Division of Rheumatology, Baltimore, Maryland, United States

Shangzhu Zhang

• Madhu, Roopa, Brigham and Women's Hospital, Boston, Massachusetts, United States

Roopa Madhu, PhD

• O'Malley, Tyler, Exagen Inc, Vista, California, United States

Tyler O'Malley

• Izmirly, Peter, New York University, New York, New York, United States

Peter Izmirly, MD

• Belmont, H. Michael, New York University, New York, New York, United States

H. Michael Belmont, DrMed

• Furie, Richard, Northwell Health, New Hyde Park, New York, United States

Richard Furie, MD

• Schwartz, Noa, Albert Einstein College of Medicine, New York, New York, United States

Noa Schwartz, MD, MSc

• Putterman, Chaim, Albert Einstein College of Medicine, New York, New York, United States

Chaim Putterman, MD, MBA

• Barnas, Jennifer L, University of Rochester Medical Center, Rochester, New York, United States

Jennifer L Barnas, MD, PhD

• Anolik, Jennifer H., University of Rochester Medical Center, Rochester, New York, United States

Jennifer H. Anolik, MD

• French, Sarah, University of California San Francisco, San Francisco, California, United States

Sarah French, MD

• Dall'Era, Maria, University of California San Francisco, San Francisco, California, United States

Maria Dall'Era, MD

• James, Judith A, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma, United States

Judith A James, MD, PhD

• Guthridge, Joel M, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma, United States

Joel M Guthridge, PhD

• Nerenberg, Mike, Exagen Inc, Vista, California, United States

Mike Nerenberg, MD

• Wei, Kevin, Brigham and Women's Hospital, Boston, Massachusetts, United States

Kevin Wei, MD, PhD

• Eisenhaure, Thomas, Broad Institute, Cambridge, Massachusetts, United States

Thomas Eisenhaure

• Bogle, Rachael, University of Michigan, Ann Arbor, Michigan, United States

Rachael Bogle, MS

• Tsoi, Lam, University of Michigan, Ann Arbor, Michigan, United States

Lam Tsoi, MS, PhD

• Buyon, Jill P., New York University, New York, New York, United States

Jill P. Buyon, MD

• Rovin, Brad, The Ohio State University Wexner Medical Center, Columbus, Ohio, United States

Brad Rovin, FASN

• Petri, Michelle, Johns Hopkins Medicine Division of Rheumatology, Baltimore, Maryland, United States

Michelle Petri, MD, MPH

Group or Team Name

• The Accelerating Medicines Partnership in RA/SLE and Autoimmune and Immune-Mediated Disease Program.

Background

Kidney survival is the ultimate goal in lupus nephritis (LN), but long-term predictors remain understudied and proteinuria is imprecise. We studied urinary biomarkers predictive of future kidney function loss.

Methods

We followed 170 LN patients for up to 7.8 years (median 4.9). eGFR loss was defined as ≥40% sustained decline from baseline or ESKD. Urine samples collected at biopsy and months 3, 6, and 12 were assayed for 1200 proteins (RayBiotech). Single-cell and spatial transcriptomics (Xenium) were used to localize biomarker expression.

Results

53/170 patients (31%) developed eGFR loss. At month 3, Tenascin C emerged as the strongest predictor of eGFR loss and remained elevated through month 12. Inflammatory and fibrosis-associated markers such as CD163, CD206, IL6, FABP4, and IGFBP-6 were persistenly associated with risk. Single-cell and spatial transcriptomics localized Tenascin C to myofibroblasts, suggesting a profibrotic role. An 11-protein classifier (including Tenascin C) achieved excellent performance (AUC=0.91), stratifying patients into high vs low risk at any follow up time point. The risk score outperformed proteinuria and identified high-risk patients in both proteinuric responders and nonresponders.

Conclusion

Urinary Tenascin C, a marker of myofibroblast activation, robustly predicts kidney function loss in LN. Persistent CD163/CD206 elevation suggests ongoing macrophage-driven fibrosis. A urine panel outperformed proteinuria supporting early biomarker-guided strategies to personalize care, refine clinical trials and prevent irreversible damage.

Funding

• NIDDK Support

Digital Object Identifier (DOI)

• doi: 10.1681/ASN.2025314tx12w