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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Main Authors: Jordanka Homolová, Ľubica Janovičová, Barbora Konečná, Barbora Vlková, Peter Celec, Ľubomíra Tóthová, Janka Bábíčková
Format: Article
Language:English
Published: MDPI AG 2020-03-01
Series:Diagnostics
Subjects:
Online Access:https://www.mdpi.com/2075-4418/10/3/152
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spelling 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&#8212;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&#8722;reperfusion injury (IRI) and bilateral nephrectomy (BNx). Total ecDNA was significantly higher in BUO (<i>p</i> &lt; 0.05) and GLY (<i>p</i> &lt; 0.05) compared to the respective control groups. ncDNA was significantly higher in BUO (<i>p</i> &lt; 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&#8212;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&#8722;reperfusion injury (IRI) and bilateral nephrectomy (BNx). Total ecDNA was significantly higher in BUO (<i>p</i> &lt; 0.05) and GLY (<i>p</i> &lt; 0.05) compared to the respective control groups. ncDNA was significantly higher in BUO (<i>p</i> &lt; 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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