Circulating cell-free DNA in hemodialysis patients predicts mortality

Tovbin, David; Novack, Victor; Wiessman, Maya; Elkadir, Amir Abd; Zlotnik, Moshe; Douvdevani, Amos

doi:10.1093/ndt/gfs255

Cited by 43 publications

(46 citation statements)

References 27 publications

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“…This method was tested in comparison with the gold standard, QPCR to β-globin and was found to be in good correlation of R 2 = 0.9987 (p<0.0001) as previously described [15]. The normal cutoff level of 850 ng/ml was established in our previous studies [5], [8], [15], [18].…”

Section: Methodsmentioning

confidence: 76%

“…In contrast, measurement of DNA concentration by our assay requires only the mixture of a small serum or plasma sample with a fluorescent dye; collected blood can be kept at room temperature for few hours, no extraction or incubation are needed and results are promptly available [15]. Our assay was used in previous clinical studies by us [5], [8], [15], [18], [26] and others [27], [28].…”

Section: Discussionmentioning

confidence: 99%

“…Circulating cell-free DNA (CFD), a product of cell necrosis, apoptosis and active secretion, is being investigated as a new reliable marker for assessing prognosis in various pathologies, including cancer, trauma and chronic renal failure (CRF) treated by hemodialysis [5], [6], [7], [8]. Several studies evaluated the prognostic accuracy of CFD for ICU general-patients and septic-patients for death prediction and found good correlation with other outcome predicting scores and markers, such as APACHE, SOFA and CRP level [9], [10], [11], [12], [13], [14].…”

Section: Introductionmentioning

confidence: 99%

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Admission Cell Free DNA Levels Predict 28-Day Mortality in Patients with Severe Sepsis in Intensive Care

et al. 2014

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AimThe aim of the current study is to assess the mortality prediction accuracy of circulating cell-free DNA (CFD) level at admission measured by a new simplified method.Materials and MethodsCFD levels were measured by a direct fluorescence assay in severe sepsis patients on intensive care unit (ICU) admission. In-hospital and/or twenty eight day all-cause mortality was the primary outcome.ResultsOut of 108 patients with median APACHE II of 20, 32.4% have died in hospital/or at 28-day. CFD levels were higher in decedents: median 3469.0 vs. 1659 ng/ml, p<0.001. In multivariable model APACHE II score and CFD (quartiles) were significantly associated with the mortality: odds ratio of 1.05, p = 0.049 and 2.57, p<0.001 per quartile respectively. C-statistics for the models was 0.79 for CFD and 0.68 for APACHE II. Integrated discrimination improvement (IDI) analyses showed that CFD and CFD+APACHE II score models had better discriminatory ability than APACHE II score alone.ConclusionsCFD level assessed by a new, simple fluorometric-assay is an accurate predictor of acute mortality among ICU patients with severe sepsis. Comparison of CFD to APACHE II score and Procalcitonin (PCT), suggests that CFD has the potential to improve clinical decision making.

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Section: Methodsmentioning

confidence: 76%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Admission Cell Free DNA Levels Predict 28-Day Mortality in Patients with Severe Sepsis in Intensive Care

et al. 2014

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“…Additionally, cell-free DNA is also a marker of NET formation, as neutrophils extrude cell-free DNA and histone-bound DNA from their nuclei. In fact, increased levels of cell-free DNA have been reported in the dialysis condition [10,11,18] . In our study, several patients showed high levels of cell-free DNA as compared to controls; however, the overall level of cell-free DNA was not significantly increased in HD patients.…”

Section: Discussionmentioning

confidence: 99%

“…The neutrophil extracellular trap (NET) not only entraps pathogens and platelets but also promotes inflammatory reactions [9] . Additionally, circulating cell-free DNA has been demonstrated to promote inflammation and to predict mortality in HD patients [10,11] . Fortunately, the circulating level of neutrophil elastase, a protease released from azurophilic granules of activated neutrophils, can be used as a marker of neutrophil activation [12] .…”

Section: Introductionmentioning

confidence: 99%

Significance of the DNA-Histone Complex Level as a Predictor of Major Adverse Cardiovascular Events in Hemodialysis Patients: The Effect of Uremic Toxin on DNA-Histone Complex Formation

Jeong

Kim²,

Gu³

et al. 2015

Blood Purif

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Background: Neutrophils can release the DNA-histone complex into circulation following exposure to inflammatory stimuli. This prospective study investigated whether the DNA-histone complex and other biomarkers could predict major cardiovascular adverse events (MACEs) in hemodialysis (HD) patients. Methods: The levels of circulating DNA-histone complexes, cell-free DNA, interleukin (IL)-6, and neutrophil elastase were measured in 60 HD patients and 28 healthy controls. MACE was assessed at 24 months. Uremic toxin-induced neutrophil released contents were measured in vitro. Results: Compared with controls, HD patients showed higher levels of DNA-histone complexes and IL-6. The DNA-histone complex level was inversely associated with the Kt/V. In a multivariable Cox analysis, the high level of DNA-histone complexes was a significant independent predictor of MACE. The uremic toxins induced DNA-histone complex formation in normal neutrophils in vitro. Conclusion: The DNA-histone complex is a potentially useful marker to predict MACE in HD patients. Uremic toxins induced DNA-histone complex formation in vitro.

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Correlation between variant allele frequency and mean tumor molecules with tumor burden in patients with solid tumors

Kalashnikova,

Aushev,

Malashevich

et al. 2023

Molecular Oncology

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Several studies have demonstrated the prognostic value of circulating tumor DNA (ctDNA); however, the correlation of mean tumor molecules (MTM)/ml of plasma and mean variant allele frequency (mVAF; %) with clinical parameters is yet to be understood. In this study, we analyzed ctDNA data in a pan‐cancer cohort of 23 543 patients who had ctDNA testing performed using a personalized, tumor‐informed assay (Signatera™, mPCR‐NGS assay). For ctDNA‐positive patients, the correlation between MTM/ml and mVAF was examined. Two subanalyses were performed: (a) to establish the association of ctDNA with tumor volume and (b) to assess the correlation between ctDNA dynamics and patient outcomes. On a global cohort, a positive correlation between MTM/ml and mVAF was observed. Among 18 426 patients with longitudinal ctDNA measurements, 13.3% had discordant trajectories between MTM/ml and mVAF at subsequent time points. In metastatic patients receiving immunotherapy (N = 51), changes in ctDNA levels expressed both in MTM/ml and mVAF showed a statistically significant association with progression‐free survival; however, the correlation with MTM/ml was numerically stronger.

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Circulating cell-free DNA in hemodialysis patients predicts mortality

Abstract: Post-dialysis CFD level is an independent predictor of all-cause mortality in patients undergoing HD. We propose that CFD detection is an inexpensive applicable tool for identifying patients at risk and their follow-up.

Cited by 43 publications

References 27 publications

Admission Cell Free DNA Levels Predict 28-Day Mortality in Patients with Severe Sepsis in Intensive Care

Admission Cell Free DNA Levels Predict 28-Day Mortality in Patients with Severe Sepsis in Intensive Care

Significance of the DNA-Histone Complex Level as a Predictor of Major Adverse Cardiovascular Events in Hemodialysis Patients: The Effect of Uremic Toxin on DNA-Histone Complex Formation

Correlation between variant allele frequency and mean tumor molecules with tumor burden in patients with solid tumors

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