Cell-free DNA: the role in pathophysiology and as a biomarker in kidney diseases

Celec, Peter; Vlková, Barbora; Lauková, Lucia; Bábíčková, Janka; Boor, Peter

doi:10.1017/erm.2017.12

Cited by 61 publications

(58 citation statements)

References 191 publications

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“…Deoxyribonuclease activity is inversely proportional to the amount of cfDNA. Low deoxyribonuclease activity in plasma could be the cause of increased amount of cfDNA in some diseases . The highest deoxyribonuclease activity among all tested tissues and body fluids was found in urine.…”

Section: Discussionmentioning

confidence: 93%

Dynamics of early post-operative plasma ddcfDNA levels in kidney transplantation: a single-center pilot study

et al. 2018

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Donor-derived cell-free DNA (ddcfDNA) is reported to be a promising noninvasive biomarker for acute rejection in organ transplant. However, studies on monitoring ddcfDNA dynamics during the early periods after organ transplantation are scarce. Our study assessed the dynamic variation in ddcfDNA in early period with various types and status of kidney transplantation. Target region capture sequencing used identifies ddcfDNA level in 21 kidney transplant recipients. Median ddcfDNA level was 20.69% at the initial time post-transplant, and decreased to 5.22% on the first day and stayed at the stable level after the second day. The ddcfDNA level in DCD (deceased donors) group (44.99%) was significantly higher than that in LDRT (living donor) group (10.24%) at initial time, P < 0.01. DdcfDNA level in DGF (delayed graft function) recipients was lower (23.96%) than that in non-DGF (47.74%) at the initial time, P = 0.89 (19.34% in DGF and 4.46% in non-DGF on the first day, P = 0.17). DdcfDNA level at initial time significantly correlated with serum creatinine (r = 0.219, P = 0.032) and warm ischemia time (r = 0.204, P = 0.040). Plasma ddcfDNA level decreased rapidly follow an L-shaped curve post-transplant, and level in DGF declined slower than non-DGF. The rebound of ddcfDNA level may indicate the occurrence of acute rejection.

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Section: Discussionmentioning

confidence: 93%

Dynamics of early post-operative plasma ddcfDNA levels in kidney transplantation: a single-center pilot study

et al. 2018

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“…The estimated half-life of cfDNA in circulating blood varies from several minutes (e.g., 4 min after hemodialysis cessation) to 1-2 h. [103][104][105][106] Interestingly, clearance of fetal DNA from maternal blood occurs in a bi-phasic manner: first, a rapid phase occurs with a mean half-life of~10 min to 1 h; then, a second slow phase occurs with a mean half-life of~13 h. 107 The half-life of the ctDNA level after surgical tumor resection in a pre-clinical rabbit model of head and neck cancer was 23-52 min. 25 A serial analysis of ctDNA in patients with colorectal cancer showed a halflife of 114 min.…”

Section: Clearance Of Cfdnamentioning

confidence: 99%

Life and death of circulating cell-free DNA

Kustanovich

Schwartz

Peretz

et al. 2019

Cancer Biology & Therapy

348

293

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Tumor-specific, circulating cell-free DNA in liquid biopsies is a promising source of biomarkers for minimally invasive serial monitoring of treatment responses in cancer management. We will review the current understanding of the origin of circulating cell-free DNA and different forms of DNA release (including various types of cell death and active secretion processes) and clearance routes. The dynamics of extracellular DNA in blood during therapy and the role of circulating DNA in pathophysiological processes (tumor-associated inflammation, NETosis, and pre-metastatic niche development) provide insights into the mechanisms that contribute to tumor development and metastases formation. Better knowledge of circulating tumor-specific cell-free DNA could facilitate the development of new therapeutic and diagnostic options for cancer management. ARTICLE HISTORY

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“…Donor cfDNA is derived from DNA fragments released from necrotic or apoptotic cells in injured donor tissues (9). Donor cfDNAs possess identical properties to those of cfDNA in general: they are approximately 85-200 base pairs in size (10), and are metabolized and cleared in the liver (9,11) independent of the renal function, which is probably due to their negative ions rendering them non-filterable through the glomeruli (12). Donor cfDNA levels rise in solid allografts following ischemia-reperfusion injury (8,13,14).…”

Section: Introductionmentioning

confidence: 99%

Diagnostic Performance of Donor-Derived Plasma Cell-Free DNA Fraction for Antibody-Mediated Rejection in Post Renal Transplant Recipients: A Prospective Observational Study

Zhang

Zheng

et al. 2020

Front. Immunol.

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Objective: To evaluate the diagnostic performance of donor-derived plasma cell-free DNA (cfDNA) in discriminating antibody-mediated rejection (ABMR) or de novo donorspecific antibodies (DSA) without histological lesions in kidney allograft recipients. Methods:In this prospective single center observational study, we enrolled kidney allograft recipients between November, 2016 and September, 2017 at the First Affiliated Hospital of Sun Yat-sen University. Kidney allograft recipients with ABMR, de novo DSA but no histological lesions or negative DSA, and stable renal function were included. The plasma cfDNA fraction was measured using a targeted, single nucleotide polymorphism (SNP)-based assay. Pathological diagnosis was made according to the 2015 Banff Kidney Rejection Classification. The area under the ROC curve (AUC-ROC) was determined using the bootstrapping method to estimate median and 95% confidence interval (95% CI). The sensitivity, specificity and Youden index, positive predictive value (PPV), and negative predictive value (NPV) were calculated for specific cfDNA fractions.Results: Totally 37 consecutive patients received kidney allografts, including 18 recipients in the ABMR group and 19 recipients in the stable allograft group (7 DSApositive and 12 DSA-negative). All patients in the ABMR group were DSA positive and 7 patients in the stable group were DSA positive but had no pathologically proven ABMR. The median donor-derived plasma cfDNA fraction was 2.4% (Q1 1.52% -Q3 3.70%) in the ABMR group, and was significantly higher than that of the stable group (0.65%, Q1 Frontiers in Immunology | www.frontiersin.org February 2020 | Volume 11 | Article 342 Zhang et al.Donor-Derived cfDNA in Kidney ABMR 0.57% -Q3 0.97%; P < 0.001), but comparable with that of the DSA-positive patients in the stable allograft group (P = 0.074). The AUC-ROC of cfDNA was 0.90 (95% CI, 0.79-0.98). When a cfDNA threshold of 1% was chosen, it had a sensitivity of 88.9% and a specificity of 73.7%. The PPV was 76.2% and the NPV was 87.5%.Conclusion: Donor-derived plasma cfDNA fraction increased in kidney allograft recipients with ABMR. Detection of donor-derived plasma cfDNA fraction may contribute to the discrimination between ABMR and stable renal allograft function and may aid early recognition of earlier stage antibody-mediated injury.

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Cell-free DNA: the role in pathophysiology and as a biomarker in kidney diseases

Cited by 61 publications

References 191 publications

Dynamics of early post-operative plasma ddcfDNA levels in kidney transplantation: a single-center pilot study

Dynamics of early post-operative plasma ddcfDNA levels in kidney transplantation: a single-center pilot study

Life and death of circulating cell-free DNA

Diagnostic Performance of Donor-Derived Plasma Cell-Free DNA Fraction for Antibody-Mediated Rejection in Post Renal Transplant Recipients: A Prospective Observational Study

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