A cross-sectional study of the role of epithelial cell injury in kidney transplant outcomes

Halloran, Philip F. (author), Arnol, Miha (author), Kojc, Nika (author), Večerić-Haler, Željka (author)

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.

• Language: English
• Keywords: molecular diagnosis, nephrology, organ transplantation, transplantation
• Work type: Article
• Typology: 1.01 - Original Scientific Article
• Organization: MF - Faculty of Medicine
• Publication status: Published
• Publication version: Version of Record
• Year: 2025
• Number of pages: 22 str.
• Numbering: Vol. 10, iss. 10, art. e188658
• PID: 20.500.12556/RUL-185582
• UDC: 616-07
• ISSN on article: 2379-3708
• COBISS.SI-ID: 238840323
• Publication date in RUL: 11.08.2026

Record is a part of a journal

• Title: JCI insight
• Shortened title: JCI insight
• Publisher: American Society for Clinical Investigtion
• ISSN: 2379-3708
• COBISS.SI-ID: 56135427

Licences

• License: CC BY 4.0, Creative Commons Attribution 4.0 International
• Link: http://creativecommons.org/licenses/by/4.0/
• Description: This is the standard Creative Commons license that gives others maximum freedom to do what they want with the work as long as they credit the author.

Secondary language

• Language: Slovenian
• Keywords: molekularna diagnoza, nefrologija, presaditev organov, transplantacija