Across-sectional study of the role of epithelial cell injury in kidney transplant outcomes
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00023001%3A_____%2F25%3A00085697" target="_blank" >RIV/00023001:_____/25:00085697 - isvavai.cz</a>
Result on the web
<a href="https://insight.jci.org/articles/view/188658/pdf" target="_blank" >https://insight.jci.org/articles/view/188658/pdf</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1172/jci.insight.188658" target="_blank" >10.1172/jci.insight.188658</a>
Alternative languages
Result language
angličtina
Original language name
Across-sectional study of the role of epithelial cell injury in kidney transplant outcomes
Original language description
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, AI(I-induced changes, failed repair, and inflammation; and PC3, a response involving epithelial remodeling without inflammation. Increasing kidney age amplifies PC1 and PC3. TRIAL REGISTRATION. INTERCOMEX (ClinicalTrials.gov NCT01299168); Trifecta-I(idney (ClinicalTrials.gov NCT04239703).
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
30213 - Transplantation
Result continuities
Project
—
Continuities
N - Vyzkumna aktivita podporovana z neverejnych zdroju
Others
Publication year
2025
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
JCI insight
ISSN
2379-3708
e-ISSN
2379-3708
Volume of the periodical
10
Issue of the periodical within the volume
10
Country of publishing house
US - UNITED STATES
Number of pages
23
Pages from-to
"art. no. e188658"
UT code for WoS article
001501751000001
EID of the result in the Scopus database
2-s2.0-105006603673