Kidney Week

Abstract: TH-PO0979

Cross-Species Profiling Identifies Persistent Tubular Injury Programs Associated with Poor Kidney Allograft Outcome After T-Cell-Mediated Rejection

Session Information

• Transplantation: Basic - Immune Biology, Tissue Injury, and Emerging Technologies
  October 22, 2026 | Location: Exhibit Hall A, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Transplantation

• 2001 Transplantation: Basic

Authors

• Jahn, Lorenz, Medizinische Hochschule Hannover, Hanover, NDS, Germany

Lorenz Jahn

• Pfefferkorn, Anna Maria, Charite - Universitatsmedizin Berlin, Berlin, BE, Germany

Anna Maria Pfefferkorn, MS, MSc

• Gauthier, Patrick T., University of Alberta Alberta Transplant Applied Genomics Centre, Edmonton, Alberta, Canada

Patrick T. Gauthier, PhD

• Kulow, Vera Anna, Charite - Universitatsmedizin Berlin Institut fur Translationale Physiologie, Berlin, BE, Germany

Vera Anna Kulow

• Roeles, Johannes, Medizinische Hochschule Hannover, Hanover, NDS, Germany

Johannes Roeles, MD, DrMed

• Müller-Bötticher, Niklas, Berlin Institute of Health at Charité – Universitätsmedizin Berlin, Center of Digital Health, Berlin, BE, Germany

Niklas Müller-Bötticher, MSc

• Gerhardt, Louisa Maria Sophie, Department of Medicine V, University Medical Centre Mannheim, University of Heidelberg, Mannheim, BW, Germany

Louisa Maria Sophie Gerhardt, MD

• Leiz, Janna, Medizinische Hochschule Hannover, Hanover, NDS, Germany

Janna Leiz

• Sarfraz, Sadia, Charite - Universitatsmedizin Berlin, Berlin, BE, Germany

Sadia Sarfraz, APN

• Plumbom, Izabela, Core Unit Genomics, Berlin Institute of Health at Charité, Berlin, BE, Germany

Izabela Plumbom, MSc

• Greite, Robert, Medizinische Hochschule Hannover, Hanover, NDS, Germany

Robert Greite, MD

• Lovric, Svjetlana, Medizinische Hochschule Hannover, Hanover, NDS, Germany

Svjetlana Lovric, MD

• Schmitz, Jessica, Medizinische Hochschule Hannover, Hanover, NDS, Germany

Jessica Schmitz

• Scheffner, Irina, Medizinische Hochschule Hannover, Hanover, NDS, Germany

Irina Scheffner, MS

• Sauer, Igor M., Charite - Universitatsmedizin Berlin, Berlin, BE, Germany

Igor M. Sauer, MD, DrMed, PhD

• Aigner, Felix, Charite - Universitatsmedizin Berlin, Berlin, BE, Germany

Felix Aigner, DrMed, MBA

• Altmüller, Janine, Core Unit Genomics, Berlin Institute of Health at Charité, Berlin, BE, Germany

Janine Altmüller, MD

• Conrad, Thomas, Core Unit Genomics, Berlin Institute of Health at Charité, Berlin, BE, Germany

Thomas Conrad, PhD

• Gwinner, Wilfried, Medizinische Hochschule Hannover, Hanover, NDS, Germany

Wilfried Gwinner, MD

• Ishaque, Naveed, Berlin Institute of Health at Charité – Universitätsmedizin Berlin, Center of Digital Health, Berlin, BE, Germany

Naveed Ishaque, MSc, PhD

• Fähling, Michael, Charite - Universitatsmedizin Berlin Institut fur Translationale Physiologie, Berlin, BE, Germany

Michael Fähling, PhD

• Schmidt-Ott, Kai M., Medizinische Hochschule Hannover, Hanover, NDS, Germany

Kai M. Schmidt-Ott, MD, FASN

• Halloran, Philip F., University of Alberta Alberta Transplant Applied Genomics Centre, Edmonton, Alberta, Canada

Philip F. Halloran, MD, PhD

• Ashraf, Muhammad Imtiaz, Charite - Universitatsmedizin Berlin, Berlin, BE, Germany

Muhammad Imtiaz Ashraf, PhD

• Hinze, Christian, Medizinische Hochschule Hannover, Hanover, NDS, Germany

Christian Hinze, MD, DrMed

Background

T cell-mediated rejection (TCMR) remains a major barrier to long-term kidney allograft survival. Although it often shows histologic remission after treatment, TCMR still confers substantial risk of graft dysfunction and loss, suggesting that clinically relevant injury extends beyond the immune infiltrate itself.

Methods

We induced acute TCMR in murine allogeneic kidney transplants with syngeneic controls and profiled grafts 7 days after transplantation by histology, single-nucleus RNA sequencing, and spatial transcriptomics. This multimodal strategy was used to define injury-associated tubular cell states, their spatial organization, and their relationship to infiltrating immune cells. Murine findings were compared with human TCMR and stable allograft biopsies analyzed by snRNA-seq, and selected observations were validated by immunofluorescence. Clinical relevance was assessed in large kidney transplant bulk transcriptomic cohorts using single-cell deconvolution and injury-state gene-set analyses linked to rejection phenotypes and graft outcome.

Results

Allogeneic mouse kidneys developed histopathological features of TCMR and showed the strongest transcriptional remodeling in proximal tubules (PT) and thick ascending limbs (TAL). Subclustering identified distinct PT and TAL injury states, including severely injured populations with heterogeneous spatial distribution and distinct relationships to infiltrating leukocytes and local cellular microenvironments. Cross-species analyses demonstrated conserved tubular injury states in human TCMR, including human counterparts of the most severely injured murine populations. Importantly, higher abundance of severe epithelial injury states was associated with inferior allograft survival in large human bulk transcriptomic cohorts. In addition, injury-related epithelial signatures persisted in a subset of cases despite apparent resolution of TCMR, indicating ongoing tissue injury beyond overt rejection activity.

Conclusion

Cross-species multimodal profiling identifies conserved PT and TAL injury states as clinically relevant determinants of kidney allograft outcome in TCMR. These findings support a model in which persistent tubular injury contributes substantially to post-rejection graft loss and may provide a basis for improved prognostic biomarkers and therapeutic targeting.