Abstract: TH-PO0981
Spatial Pattern Identification of Reperfusion and Ischemia of the Kidney (SPIRIT-K)
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
- Schuebel, Yael, Charite - Universitatsmedizin Berlin, Berlin, BE, Germany
- Mueller, Roman-Ulrich, University Hospital Dusseldorf, Dusseldorf, NRW, Germany
- Späth, Martin R., University Hospital Dusseldorf, Dusseldorf, NRW, Germany
- Balzer, Michael S., Universitatsklinikum Schleswig-Holstein, Kiel, SH, Germany
Group or Team Name
- Balzer lab
Background
Renal ischemia-reperfusion injury (IRI) is an unavoidable consequence of kidney transplantation and a key driver of long-term graft failure. In animal models dietary preconditioning has proven to be very effective in prevention of IRI. However, a spatially resolved understanding of human IRI within intact and injured tissue architecture of the same individuals in the context of the dietary interventions remains lacking.
Methods
We performed high-resolution spatial transcriptomics (Xenium) on 16 human kidney samples collected during living kidney transplantations directly after nephrectomy (ischemia) and directly after transplantation (reperfusion) in the context of dietary interventions, including ad libitum diet, caloric restriction (CR), and protein restriction (PR).
Results
We resolved major renal cell populations, including tubular epithelial and diverse immune subsets. Cell composition was comparable across groups during ischemia. In individuals on ad libitum diet, reperfusion induced a marked loss of healthy epithelial cells, including proximal tubule (PT), distal convoluted tubule (DCT), and podocytes, alongside expansion of injured PT and thick ascending limb (TAL) cells. These injury-associated shifts were absent under CR and PR. CR was associated with reduced accumulation of injured PT and TAL cells and preservation of healthy PT cells. Notably, podocyte loss was prevented exclusively under PR, indicating a distinct cell type-specific protective effect. Despite these differences, the overall cellular landscape remained similar between CR and PR during reperfusion. Spatial neighborhood analysis revealed that metabolic adaptation under dietary restriction reshapes injury-associated niches and modulates immune-epithelial crosstalk.
Conclusion
This study provides the first spatially resolved map of human renal IRI in the context of diet-dependent cell type-specific spatial effects in the human kidney. Our findings identify metabolism-driven remodeling of cellular interactions as a central feature of injury modulation, highlighting spatially defined immune-epithelial crosstalk as a potential therapeutic target.
Acknowledgment
Funding: Sonnenfeld foundation (YS), Dr. Werner Jackstaedt foundation (MSB), European Research Council (MSB).
Funding
- Private Foundation Support