Plasma Concentrations of Extracellular DNA in Acute Kidney Injury
Current diagnostic methods of acute kidney injury (AKI) have limited sensitivity and specificity. Tissue injury has been linked to an increase in the concentrations of extracellular DNA (ecDNA) in plasma. A rapid turnover of ecDNA in the circulation makes it a potential marker with high sensitivity....
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doaj-92884454779a4c798504c696aa7f13d92020-11-25T03:50:59ZengMDPI AGDiagnostics2075-44182020-03-0110315210.3390/diagnostics10030152diagnostics10030152Plasma Concentrations of Extracellular DNA in Acute Kidney InjuryJordanka Homolová0Ľubica Janovičová1Barbora Konečná2Barbora Vlková3Peter Celec4Ľubomíra Tóthová5Janka Bábíčková6Institute of Molecular Biomedicine, Faculty of Medicine, Comenius University, 81108 Bratislava, SlovakiaInstitute of Molecular Biomedicine, Faculty of Medicine, Comenius University, 81108 Bratislava, SlovakiaInstitute of Molecular Biomedicine, Faculty of Medicine, Comenius University, 81108 Bratislava, SlovakiaInstitute of Molecular Biomedicine, Faculty of Medicine, Comenius University, 81108 Bratislava, SlovakiaInstitute of Molecular Biomedicine, Faculty of Medicine, Comenius University, 81108 Bratislava, SlovakiaInstitute of Molecular Biomedicine, Faculty of Medicine, Comenius University, 81108 Bratislava, SlovakiaInstitute of Molecular Biomedicine, Faculty of Medicine, Comenius University, 81108 Bratislava, SlovakiaCurrent diagnostic methods of acute kidney injury (AKI) have limited sensitivity and specificity. Tissue injury has been linked to an increase in the concentrations of extracellular DNA (ecDNA) in plasma. A rapid turnover of ecDNA in the circulation makes it a potential marker with high sensitivity. This study aimed to analyze the concentration of ecDNA in plasma in animal models of AKI. Three different fractions of ecDNA were measured—total ecDNA was assessed fluorometrically, while nuclear ecDNA (ncDNA) and mitochondrial DNA (mtDNA) were analyzed using quantitative real-time PCR. AKI was induced using four different murine models of AKI-bilateral ureteral obstruction (BUO), glycerol-induced AKI (GLY), ischemia−reperfusion injury (IRI) and bilateral nephrectomy (BNx). Total ecDNA was significantly higher in BUO (<i>p</i> < 0.05) and GLY (<i>p</i> < 0.05) compared to the respective control groups. ncDNA was significantly higher in BUO (<i>p</i> < 0.05) compared to SHAM. No significant differences in the concentrations of mtDNA were found between the groups. The plasma concentrations of different fractions of ecDNA are dependent on the mechanism of induction of AKI and warrant further investigation as potential surrogate markers of AKI.https://www.mdpi.com/2075-4418/10/3/152cell free dnauremiaischemianephrectomyureteral obstruction |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Jordanka Homolová Ľubica Janovičová Barbora Konečná Barbora Vlková Peter Celec Ľubomíra Tóthová Janka Bábíčková |
spellingShingle |
Jordanka Homolová Ľubica Janovičová Barbora Konečná Barbora Vlková Peter Celec Ľubomíra Tóthová Janka Bábíčková Plasma Concentrations of Extracellular DNA in Acute Kidney Injury Diagnostics cell free dna uremia ischemia nephrectomy ureteral obstruction |
author_facet |
Jordanka Homolová Ľubica Janovičová Barbora Konečná Barbora Vlková Peter Celec Ľubomíra Tóthová Janka Bábíčková |
author_sort |
Jordanka Homolová |
title |
Plasma Concentrations of Extracellular DNA in Acute Kidney Injury |
title_short |
Plasma Concentrations of Extracellular DNA in Acute Kidney Injury |
title_full |
Plasma Concentrations of Extracellular DNA in Acute Kidney Injury |
title_fullStr |
Plasma Concentrations of Extracellular DNA in Acute Kidney Injury |
title_full_unstemmed |
Plasma Concentrations of Extracellular DNA in Acute Kidney Injury |
title_sort |
plasma concentrations of extracellular dna in acute kidney injury |
publisher |
MDPI AG |
series |
Diagnostics |
issn |
2075-4418 |
publishDate |
2020-03-01 |
description |
Current diagnostic methods of acute kidney injury (AKI) have limited sensitivity and specificity. Tissue injury has been linked to an increase in the concentrations of extracellular DNA (ecDNA) in plasma. A rapid turnover of ecDNA in the circulation makes it a potential marker with high sensitivity. This study aimed to analyze the concentration of ecDNA in plasma in animal models of AKI. Three different fractions of ecDNA were measured—total ecDNA was assessed fluorometrically, while nuclear ecDNA (ncDNA) and mitochondrial DNA (mtDNA) were analyzed using quantitative real-time PCR. AKI was induced using four different murine models of AKI-bilateral ureteral obstruction (BUO), glycerol-induced AKI (GLY), ischemia−reperfusion injury (IRI) and bilateral nephrectomy (BNx). Total ecDNA was significantly higher in BUO (<i>p</i> < 0.05) and GLY (<i>p</i> < 0.05) compared to the respective control groups. ncDNA was significantly higher in BUO (<i>p</i> < 0.05) compared to SHAM. No significant differences in the concentrations of mtDNA were found between the groups. The plasma concentrations of different fractions of ecDNA are dependent on the mechanism of induction of AKI and warrant further investigation as potential surrogate markers of AKI. |
topic |
cell free dna uremia ischemia nephrectomy ureteral obstruction |
url |
https://www.mdpi.com/2075-4418/10/3/152 |
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