Plasma Concentrations of Extracellular DNA in Acute Kidney Injury

Jordanka Homolová,Janka Bábíčková,Ľubica Janovičová,Barbora Vlková,Barbora Konečná,Ľubomíra Tóthová,Peter Celec

doi:10.3390/diagnostics10030152

Jordanka Homolová, Janka Bábíčková + Show 5 more

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https://doi.org/10.3390/diagnostics10030152

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Journal: Diagnostics	Publication Date: Mar 11, 2020
Citations: 14	License type: CC BY 4.0

Affiliation: Comenius University Bratislava, University of Bergen

Abstract

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 (p < 0.05) and GLY (p < 0.05) compared to the respective control groups. ncDNA was significantly higher in BUO (p < 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.

Highlights

Acute kidney injury (AKI) is a serious, often life-threatening condition with a multifactorial origin and increasing incidence [1,2]
In the glycerol-induced acute kidney injury (AKI) (GLY), plasma creatinine was higher by +146% and blood urea nitrogen (BUN) by +30% compared to Control mice (CTRL) group
P = 0.16; t = 4.53 and t = 1.62, respectively). Both creatinine and BUN were significantly different in the ischemia–reperfusion injury (IRI) model (p < 0.001 both; F = 26.73 and F = 142.26, respectively)

Summary

Introduction

Acute kidney injury (AKI) is a serious, often life-threatening condition with a multifactorial origin and increasing incidence [1,2]. The estimated incidence of AKI in hospitalized patients is one in five adults and one in three children and rising [2,3]. AKI is a common complication of major surgeries, traumas, and patients in the intensive care unit [4]. Surviving AKI is associated with declined quality of life, and it is currently considered the major risk factor for developing chronic kidney disease (CKD) [2]. Annual costs of management of AKI are estimated at USD 10 billion in the United States and USD 1.7 billion in the United Kingdom [5].

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