Dynamics of Plasma and Urinary Extracellular DNA in Acute Kidney Injury

Alexander Jančuška, Alena Potočárová, Alexandra Gaál Kovalčíková, Ľudmila Podracká, Janka Bábíčková, Peter Celec, Ľubomíra Tóthová, Alexander Jančuška, Alena Potočárová, Alexandra Gaál Kovalčíková, Ľudmila Podracká, Janka Bábíčková, Peter Celec, Ľubomíra Tóthová

Abstract

Early and reliable markers of acute kidney injury (AKI) are essential. One such candidate marker of tissue damage is extracellular DNA (ecDNA). The aim of our present study is to describe the unknown dynamics of ecDNA in an animal model of AKI. Glycerol-induced nephropathy was used to model AKI in adult male Wistar rats (n = 93). Blood and urine samples were collected 1, 3, and 24 h after model induction. Total ecDNA and its sub-cellular origin was assessed. In the plasma, total ecDNA and nuclear ecDNA were significantly increased in the AKI group already after 1 h (160% and 270%, respectively, p = 0.02 and p = 0.04). Both nuclear and mitochondrial ecDNA were higher after 3 h (180% and 170%, respectively, p = 0.002 and p = 0.005). Urinary ecDNA concentrations in the AKI group were significantly increased only 24 h after model induction (130% for total ecDNA, p = 0.009; 210% for nuclear ecDNA, p = 0.02; and 200% for mitochondrial ecDNA, p = 0.0009). Our results indicate that plasma ecDNA has the potential to serve as an early and sensitive, albeit non-specific marker of AKI. Further studies should elucidate the source of ecDNA and the dynamics of ecDNA in other animal models of AKI and patients with AKI.

Keywords: cell-free DNA; glycerol-induced nephropathy; mitochondrial DNA; non-invasive marker; rhabdomyolysis.

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Concentrations of plasma creatinine (A) and urea (B) at different time points after AKI induction. *** denotes p < 0.001. CTRL—control group; AKI—glycerol-induced acute kidney injury.
Figure 2
Figure 2
Concentrations of plasma total ecDNA (A), ncDNA (B) and mtDNA (C) at different time points after AKI induction. CTRL—control group; AKI—glycerol-induced acute kidney injury. * denotes p < 0.05. ** denotes p < 0.01.
Figure 3
Figure 3
Concentrations of urinary total ecDNA (A), ncDNA (B) and mtDNA (C) per micromole of urinary creatinine at different time points after AKI induction. * denotes p < 0.05. ** denotes p < 0.01. *** denotes p < 0.001. CTRL—control group; AKI—glycerol-induced acute kidney injury.

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