A promising application of kidney-specific cell-free DNA methylation markers in real-time monitoring sepsis-induced acute kidney injury.
Epigenetics
; 19(1): 2408146, 2024 Dec.
Article
em En
| MEDLINE
| ID: mdl-39370847
ABSTRACT
Sepsis-induced acute kidney injury (SI-AKI) is a common clinical syndrome that is associated with high mortality and morbidity. Effective timely detection may improve the outcome of SI-AKI. Kidney-derived cell-free DNA (cfDNA) may provide new insight into understanding and identifying SI-AKI. Plasma cfDNA from 82 healthy individuals, 7 patients with sepsis non-acute kidney injury (SN-AKI), and 9 patients with SI-AKI was subjected to genomic methylation sequencing. We deconstructed the relative contribution of cfDNA from different cell types based on cell-specific methylation markers and focused on exploring the association between kidney-derived cfDNA and SI-AKI.Based on the deconvolution of the cfDNA methylome SI-AKI patients displayed the elevated cfDNA concentrations with an increased contribution of kidney epithelial cells (kidney-Ep) DNA; kidney-Ep derived cfDNA achieved high accuracy in distinguishing SI-AKI from SN-AKI (AUC = 0.92, 95% CI 0.7801-1); the higher kidney-ep cfDNA concentrations tended to correlate with more advanced stages of SI-AKI; strikingly, SN-AKI patients with potential kidney damage unmet by SI-AKI criteria showed higher levels of kidney-Ep derived cfDNA than healthy individuals. The autonomous screening of kidney-Ep (n = 24) and kidney endothelial (kidney-Endo, n = 12) specific methylation markers indicated the unique identity of kidney-Ep/kidney-Endo compared with other cell types, and its targeted assessment reproduced the main findings of the deconvolution of the cfDNA methylome. Our study first demonstrates that kidney-Ep- and kidney-Endo-specific methylation markers can serve as a novel marker for SI-AKI emergence, supporting further exploration of the utility of kidney-specific cfDNA methylation markers in the study of SI-AKI.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Sepse
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Metilação de DNA
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Injúria Renal Aguda
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Ácidos Nucleicos Livres
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Rim
Limite:
Adult
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Aged
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Epigenetics
/
Epigenetics (Online)
Assunto da revista:
GENETICA
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
China
País de publicação:
Estados Unidos