20.500.12556/DiRROS-28074 A cross-sectional study of the role of epithelial cell injury in kidney transplant outcomes Background: Expression of acute kidney injury-associated (AKI-associated) transcripts in kidney transplants may reflect recent injury and accumulation of epithelial cells in "failed repair" states. We hypothesized that the phenomenon of failed repair could be associated with deterioration and failure in kidney transplants. Methods: We defined injury-induced transcriptome states in 4,502 kidney transplant biopsies injury-induced gene sets and classifiers previously developed in transplants. Results: In principal component analysis (PCA), PC1 correlated with both acute and chronic kidney injury and related inflammation and PC2 with time posttransplant. Positive PC3 was a dimension that correlated with epithelial remodeling pathways and anticorrelated with inflammation. Both PC1 and PC3 correlated with reduced survival, with PC1 effects strongly increasing over time whereas PC3 effects were independent of time. In this model, we studied the expression of 12 "new" gene sets annotated in single-nucleus RNA-sequencing studies of epithelial cells with failed repair in native kidneys. The new gene sets reflecting epithelial-mesenchymal transition correlated with injury PC1 and PC3, lower estimated glomerular filtration rate, higher donor age, and future failure as strongly as any gene sets previously derived in transplants and were independent of nephron segment of origin and graft rejection. Conclusion: These results suggest 2 dimensions in the kidney transplant response to injury: PC1, AKI-induced changes, failed repair, and inflammation; and PC3, a response involving epithelial remodeling without inflammation. Increasing kidney age amplifies PC1 and PC3. molecular diagnosis nephrology organ transplantation transplantation molekularna diagnoza nefrologija presaditev organov transplantacija true false true Angleški jezik Slovenski jezik Neznano 2026-03-09 12:42:02 2026-03-09 12:42:03 2026-03-10 03:52:35 0000-00-00 00:00:00 2025 0 0 Nasl. z nasl. zaslona; Opis vira z dne 10. 6. 2025; str. 1-22 no. 10, [article no.] e188658 Vol. 10 2025 0000-00-00 Zaloznikova Objavljeno NiDoloceno 0000-00-00 0000-00-00 0000-00-00 616-07 2379-3708 238840323 RAZ_Halloran_Philip_F._2025.pdf RAZ_Halloran_Philip_F._2025.pdf 1 8C6EFE6A4098B696EE55798B7E47F490 a141c6592f464b33621c90601b7f22b3872c54b25e55410f71868c0fa2549529 407d5354-1bad-11f1-b779-001a4af901a5 https://dirros.openscience.si/Dokument.php?lang=slv&id=41463 https://insight.jci.org/articles/view/188658 1 00500a1f-1bad-11f1-b779-001a4af901a5 https://dirros.openscience.si/Dokument.php?lang=slv&id=41461 Univerzitetni klinični center Ljubljana 0 0 0