Cell-Free Plasma DNA: A Marker for Apoptosis during Hemodialysis

Atamaniuk, Johanna; Ruzicka, Katharina; Stuhlmeier, Karl M.; Karimi, Alireza; Eigner, Manfred; Mueller, Mathias M.

doi:10.1373/clinchem.2005.058883

Cited by 57 publications

(55 citation statements)

References 14 publications

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“…The accumulation of apoptotic debris and necrotic cell remnants used to be considered a main source of cfDNA (19,20). Recently, however, there has been a gradual change in that several researchers have proposed that living cells actively release DNA (18).…”

Section: Discussionmentioning

confidence: 99%

Elevated Plasma cfDNA May be Associated with Active Lupus Nephritis and Partially Attributed to Abnormal Regulation of Neutrophil Extracellular Traps (NETs) in Patients with Systemic Lupus Erythematosus

et al. 2014

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Objective The abnormal formation and insufficient clearance of neutrophil extracellular traps (NETs) has been reported to be involved in the pathogenesis of lupus nephritis (LN). The abnormal regulation of NETs may contribute to increases in the levels of circulating cell-free DNA (cfDNA). The present study tested the hypothesis that elevated plasma cfDNA levels are related to LN. Methods Fifty-four systemic lupus erythematosus (SLE) patients and 43 control subjects were included in this study. The cfDNA concentrations were measured using the Picogreen Kit, the low-density granulocyte (LDG) percentage in peripheral blood mononuclear cells (PBMCs) was tested using a flow cytometer and the DNase I activity was measured according to the radial enzyme-diffusion method. Results The mean cfDNA concentration in the SLE group was 236.66±40.09 ng/mL, which was significantly higher than that observed in the healthy control group (187.96±40.55 ng/mL, p<0.0001). Meanwhile, the mean cfDNA concentration in the patients with LN was significantly higher than that observed in the patients without LN (247.27±46.79 ng/mL vs. 213.56±31.34 ng/mL, p=0.0094), and the mean cfDNA concentration in the patients with active LN was significantly higher than that observed in the patients with inactive LN (254.22±50.16 ng/mL vs. 215.93±29.10 ng/mL, p=0.0349). In the SLE group, the cfDNA concentration was to positively correlate with the quantitative 24-hour urinary protein (r=0.350, p=0.013), LDG (r=0.6361, p=0.0019) and neutrophil (r=0.5990, p<0.0001) levels and inversely correlate with the albumin level (r= -0.500, p<0.0001) and endogenous creatinine clearance rate (r=-0.354, p=0.044). Compared to that observed in the control group, the SLE group exhibited a significantly increased percentage of LDGs in PBMCs and a significantly decreased DNase I activity. Conclusion Our data indicate that elevated plasma cfDNA concentrations may be associated with active LN and partially attributed to the abnormal regulation of NETs in SLE patients, thus suggesting that NETs constitute an intrinsic link between cfDNA and active LN.

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Section: Discussionmentioning

confidence: 99%

Elevated Plasma cfDNA May be Associated with Active Lupus Nephritis and Partially Attributed to Abnormal Regulation of Neutrophil Extracellular Traps (NETs) in Patients with Systemic Lupus Erythematosus

et al. 2014

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“…Apoptosis, necrosis, active release, and impaired clearance have been implicated (23)(24)(25), but information regarding their role during exercise is scarce. RE has been reported to generate reactive oxygen species (ROS) and oxidative stress (26 ).…”

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confidence: 99%

Cell-Free Plasma DNA as a Novel Marker of Aseptic Inflammation Severity Related to Exercise Overtraining

et al. 2006

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Background: Circulating free plasma DNA is implicated in conditions associated with tissue injury, including exercise-induced inflammation, and thus is a potential marker for athletic overtraining. Methods: We measured free plasma DNA along with C-reactive protein (CRP), creatine kinase (CK), and uric acid (UA) in 17 recreationally trained men participating in a 12-week resistance training regimen (8 resistance multi-joint exercises selected to stress the entire musculature: bench press, squat, leg press, snatch, hang clean, dead lifts, barbell arm curls, and rowing), consisting of 4 training periods (t1, t2, t3, and t4). Results: Plasma DNA concentrations increased markedly after t1, t2, and t3 and returned to baseline after t4. There were substantial differences between t2 and t1 and between t3 and t2 plasma DNA concentrations. CRP increased by 300% after t2 and by 400% after t3 (there was no difference between t2 and t3 CRP values) compared with baseline (t0). CK increased only after t3. UA increased after t2 and t3, with a greater increase after t3. Conclusions: This study demonstrates that, after chronic excessive resistance exercise, plasma DNA concentrations increase in proportion to training load, suggesting that plasma DNA may be a sensitive marker for overtraining-induced inflammation.

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“…Several studies showed dramatic elevation of cell-free nucleic acids after hemodialysis [22][23][24]. It was suggested that it can be an effect of apoptosis being a consequence of the direct contact of cells with membranes [22].…”

Section: Discussionmentioning

confidence: 99%

Alterations in Serum MicroRNA Profile During Hemodialysis - Potential Biological Implications

Trzybulska

Eckersten

Giwercman³

et al. 2018

Cell Physiol Biochem

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Background/Aims: Hemodialysis implies significant alterations in the profile of serum components. microRNAs (miRNAs) are present in the human serum and are considered to target distant tissues where they can regulate gene expression, thus affecting homeostasis. Whether hemodialysis alters the profile of miRNAs in the serum is not known. Methods: miRNA profiling in serum samples collected before and after hemodialysis was performed using miRNA qPCR arrays. The results were subsequently validated in an independent group of 10 hemodialyzed men. miRWalk database was used to identify mRNAs targeted by the miRNAs the levels of which changed after hemodialysis. The list of mRNAs was analyzed using the DAVID and PANTHER classification systems to identify pathways controlled by these miRNAs. Results: miRNA profiling showed that the levels of the majority of circulating miRNAs were increased at least two-fold (115 out of 179 tested) while the levels of only five miRNAs were found at least two-fold lower after hemodialysis. Validation study confirmed the majority of the array results. Bioinformatics analysis of validated and significantly upregulated miRNAs revealed that gonadotropin-releasing hormone receptor, cell cycle and cell pluripotencyrelated pathways were targeted. Conclusion: Hemodialysis alters serum miRNA expression profile and this alteration may result in disruption of pathways contributing to subfertility and increased risk for cancer development being pathologies associated with hemodialysis.

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Cell-Free Plasma DNA: A Marker for Apoptosis during Hemodialysis

Cited by 57 publications

References 14 publications

Elevated Plasma cfDNA May be Associated with Active Lupus Nephritis and Partially Attributed to Abnormal Regulation of Neutrophil Extracellular Traps (NETs) in Patients with Systemic Lupus Erythematosus

Elevated Plasma cfDNA May be Associated with Active Lupus Nephritis and Partially Attributed to Abnormal Regulation of Neutrophil Extracellular Traps (NETs) in Patients with Systemic Lupus Erythematosus

Cell-Free Plasma DNA as a Novel Marker of Aseptic Inflammation Severity Related to Exercise Overtraining

Alterations in Serum MicroRNA Profile During Hemodialysis - Potential Biological Implications

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