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

Kód výsledku v 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>

Výsledek na webu

<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>

Jazyk výsledku

angličtina

Název v původním jazyce

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

Popis výsledku v původním jazyce

BACKGROUND. Expression of acute kidney injury-associated (AKI-associated) transcripts in kidney transplants may reflect recent injury and accumulation of epithelial cells in &quot;failed repair&quot; 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 &quot;new&quot; 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).

Název v anglickém jazyce

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

Popis výsledku anglicky

BACKGROUND. Expression of acute kidney injury-associated (AKI-associated) transcripts in kidney transplants may reflect recent injury and accumulation of epithelial cells in &quot;failed repair&quot; 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 &quot;new&quot; 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).

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30213 - Transplantation

Projekt

—

Návaznosti

N - Vyzkumna aktivita podporovana z neverejnych zdroju

Rok uplatnění

2025

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

JCI insight

ISSN

2379-3708

e-ISSN

2379-3708

Svazek periodika

10

Číslo periodika v rámci svazku

10

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

23

Strana od-do

"art. no. e188658"

Kód UT WoS článku

001501751000001

EID výsledku v databázi Scopus

2-s2.0-105006603673