Distinct molecular processes mediate donor-derived cell-free DNA release from kidney transplants in different disease dtates
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00023001%3A_____%2F24%3A00084808" target="_blank" >RIV/00023001:_____/24:00084808 - isvavai.cz</a>
Result on the web
<a href="https://journals.lww.com/transplantjournal/fulltext/2024/04000/distinct_molecular_processes_mediate_donor_derived.14.aspx" target="_blank" >https://journals.lww.com/transplantjournal/fulltext/2024/04000/distinct_molecular_processes_mediate_donor_derived.14.aspx</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1097/TP.0000000000004877" target="_blank" >10.1097/TP.0000000000004877</a>
Alternative languages
Result language
angličtina
Original language name
Distinct molecular processes mediate donor-derived cell-free DNA release from kidney transplants in different disease dtates
Original language description
Background. Among all biopsies in the Trifecta-Kidney Study (ClinicalTrials.gov NCT04239703), elevated plasma donor-derived cell-free DNA (dd-cfDNA) correlated most strongly with molecular antibody-mediated rejection (AMR) but was also elevated in other states: T cell-mediated rejection (TCMR), acute kidney injury (AKI), and some apparently normal biopsies. The present study aimed to define the molecular correlates of plasma dd-cfDNA within specific states. Methods. Dd-cfDNA was measured by the Prospera test. Molecular rejection and injury states were defined using the Molecular Microscope system. We studied the correlation between dd-cfDNA and the expression of genes, transcript sets, and classifier scores within specific disease states, and compared AMR, TCMR, and AKI to biopsies classified as normal and no injury (NRNI). Results. In all 604 biopsies, dd-cfDNA was elevated in AMR, TCMR, and AKI. Within AMR biopsies, dd-cfDNA correlated with AMR activity and stage. Within AKI, the correlations reflected acute parenchymal injury, including cell cycling. Within biopsies classified as MMDx Normal and archetypal No injury (NRNI), dd-cfDNA still correlated significantly with rejection- and injury-related genes. TCMR activity (eg, the TCMRProbclassifier) correlated with dd-cfDNA, but within TCMR biopsies, top gene correlations were complex and not the top TCMR-selective genes. Conclusions. In kidney transplants, elevated plasma dd-cfDNA is associated with 3 distinct molecular states in the donor tissue: AMR, recent parenchymal injury (including cell cycling), and TCMR, potentially complicated by parenchymal disruption. Moreover, subtle rejection- and injury-related changes in the donor tissue can contribute to dd-cfDNA elevations in transplants considered to have no rejection or injury.
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
30217 - Urology and nephrology
Result continuities
Project
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Continuities
N - Vyzkumna aktivita podporovana z neverejnych zdroju
Others
Publication year
2024
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Transplantation
ISSN
0041-1337
e-ISSN
1534-6080
Volume of the periodical
108
Issue of the periodical within the volume
4
Country of publishing house
US - UNITED STATES
Number of pages
13
Pages from-to
898-910
UT code for WoS article
001350902900019
EID of the result in the Scopus database
2-s2.0-85188839332