- Design
- Single-cell RNA sequencing and spatial transcriptomics study of human kidney allografts
- Population
- 20 living-donor and 6 deceased-donor kidneys before transplant; 8 matched pre- and post-transplant pairs with delayed graft function
- Primary outcome
- Immune cell populations and transcriptional programmes
- Effect
- Distinct donor macrophage and T-cell signatures in deceased-donor kidneys; interferon-stimulated recipient macrophages emerging early post-transplant
Researchers compared the immune cells in 20 living-donor and six deceased-donor kidneys before transplant using single-cell RNA sequencing, with two further deceased-donor samples examined spatially. They then followed eight matched pre- and post-transplant pairs from recipients of deceased-donor kidneys who developed delayed graft function.
Deceased-donor kidneys carried donor-derived resident macrophages with lower expression of chemokines and antigen presentation genes, and these persisted after transplant. They also showed a loss of amphiregulin-expressing natural killer cells and of CD8 T cells expressing TIGIT and NKG2A, with enrichment of NKG2D-expressing CD8 T cells and a pro-inflammatory signature. Early after transplant, a distinct interferon-stimulated macrophage population of recipient origin emerged, expressing genes consistent with recruiting recipient B and T cells.
This is a descriptive study with very small numbers and no clinical outcomes or intervention. It maps candidate pathways, and does not yet suggest a test or treatment.
- No change to the management of delayed graft function follows from this study
- Continue standard supportive care and rejection surveillance after deceased-donor transplantation
- Treat the macrophage and T-cell findings as candidate targets for future trials
- Follow transplant centre protocols for biopsy in prolonged delayed function
Why it matters
Delayed graft function is more common with deceased donors and tracks with rejection, yet has no targeted therapy.
Don't overread it
Eight post-transplant pairs and no outcome data cannot support any clinical recommendation.
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