scholarly journals The use of plasma donor-derived, cell-free DNA to monitor acute rejection after kidney transplantation

2019 ◽  
Vol 35 (4) ◽  
pp. 714-721 ◽  
Author(s):  
Els M Gielis ◽  
Kristien J Ledeganck ◽  
Amélie Dendooven ◽  
Pieter Meysman ◽  
Charlie Beirnaert ◽  
...  
Keyword(s):  
Acute Rejection ◽  
Serum Creatinine ◽  
Characteristic Curve ◽  
Area Under The Curve ◽  
Threshold Value ◽  
Nucleotide Polymorphisms ◽  
Kidney Transplant Recipients ◽  
Cell Free Dna ◽  
Free Dna ◽  
Set Up

Abstract Background After transplantation, cell-free deoxyribonucleic acid (DNA) derived from the donor organ (ddcfDNA) can be detected in the recipient’s circulation. We aimed to investigate the role of plasma ddcfDNA as biomarker for acute kidney rejection. Methods From 107 kidney transplant recipients, plasma samples were collected longitudinally after transplantation (Day 1 to 3 months) within a multicentre set-up. Cell-free DNA from the donor was quantified in plasma as a fraction of the total cell-free DNA by next generation sequencing using a targeted, multiplex polymerase chain reaction-based method for the analysis of single nucleotide polymorphisms. Results Increases of the ddcfDNA% above a threshold value of 0.88% were significantly associated with the occurrence of episodes of acute rejection (P = 0.017), acute tubular necrosis (P = 0.011) and acute pyelonephritis (P = 0.032). A receiver operating characteristic curve analysis revealed an equal area under the curve of the ddcfDNA% and serum creatinine of 0.64 for the diagnosis of acute rejection. Conclusions Although increases in plasma ddcfDNA% are associated with graft injury, plasma ddcfDNA does not outperform the diagnostic capacity of the serum creatinine in the diagnosis of acute rejection.

scholarly journals Dynamic Response of Donor-Derived Cell-Free DNA Following Treatment of Acute Rejection in Kidney Allografts

Kidney360 ◽  
2021 ◽  
pp. 10.34067/KID.0000042021
Author(s):  
Theresa K. Wolf-Doty ◽  
Roslyn B. Mannon ◽  
Emilio D. Poggio ◽  
Randall J. Hinojosa ◽  
David Hiller ◽  
...  
Keyword(s):  
Molecular Marker ◽  
Acute Rejection ◽  
Dynamic Response ◽  
Serum Creatinine ◽  
Retrospective Review ◽  
Treatment Efficacy ◽  
Cell Free Dna ◽  
Index Visit ◽  
Free Dna

BACKGROUND: The quantification of rejection treatment efficacy has been insufficient using traditional markers due in part to lagging response of serum creatinine and histologic alterations on biopsy. Donor-derived cell-free DNA (dd-cfDNA) is a molecular marker of injury that may assess allograft injury following rejection. METHODS: Retrospective review of the DART study identified 70 patients who had a clinically indicated biopsy, simultaneous dd-cfDNA measurement and at least one follow-up dd-cfDNA within 3 months post-treatment. Thirty-five patients had no biopsy-proven rejection and no rejection treatment (NR), 16 patients had no biopsy-proven rejection but did receive rejection treatment (CR), 9 patients had diagnosis of ABMR/mixed rejection on biopsy and received rejection treatment (ABMR) and 10 patients had diagnosis of TCMR and received rejection treatment (TCMR). The CR, ABMR and TCMR groups combined to form a rejection (R) group. RESULTS: In the R group, dd-cfDNA at diagnosis was 0.62% and 0.35% after 1 month (P = 0.338); 0.77% and 0.21% after 2-3 months (P = 0.002). In TCMR, dd-cfDNA at diagnosis was 1.13% and 0.37% after 1 month (P = 0.625); 0.25% and 0.12% (P = 0.004) after 2-3 months. In ABMR, dd-cfDNA at diagnosis was 1.61% and 1.20% after 1 month (P = 1.000); 3.85% and 1.32% after 2-3 months (P = 0.094). In CR, dd-cfDNA at diagnosis was 0.31% and 0.29% (P = 0.375) after 1 month; 0.38% and 0.17% after 2-3 months (P = 0.313). Lastly, in NR, dd-cfDNA at the index visit was 0.21% and 0.18% after 1 month (P = 0.097); 0.33% and 0.17% after 2-3 months (P = 0.003). Changes in serum creatinine across 1 month and 2-3 months following rejection were similar. CONCLUSIONS: dd-cfDNA may be a useful dynamic biomarker to assess the health of the kidney allograft following rejection treatment.

Response by Shah et al to Letter Regarding Article, “Cell-Free DNA to Detect Heart Allograft Acute Rejection”

Circulation ◽  
2021 ◽  
Vol 144 (10) ◽  
Author(s):  
Palak Shah ◽  
Sean Agbor-Enoh ◽  
Ilker Tunc ◽  
Steven Hsu ◽  
Stuart Russell ◽  
...  
Keyword(s):  
Acute Rejection ◽  
Cell Free Dna ◽  
Heart Allograft ◽  
Free Dna

Quick cell-free DNA testing for the prediction of postconcussion syndrome: a single-center prospective pilot trial

2021 ◽  
pp. 1-7
Author(s):  
Ido Ben Zvi ◽  
Oren Shaia Harel ◽  
Amos Douvdevani ◽  
Penina Weiss ◽  
Chen Cohen ◽  
...  
Keyword(s):  
Large Scale ◽  
Characteristic Curve ◽  
Performance Status ◽  
Pilot Trial ◽  
Normal Function ◽  
Control Group ◽  
Single Center ◽  
Postconcussion Syndrome ◽  
Cell Free Dna ◽  
Free Dna

OBJECTIVE Mild traumatic brain injury (mTBI) is a major cause of emergency room (ER) admission. Thirty percent of mTBI patients have postconcussion syndrome (PCS), and 15% have symptoms for over a year. This population is underdiagnosed and does not receive appropriate care. The authors proposed a fast and inexpensive fluorometric measurement of circulating cell-free DNA (cfDNA) as a biomarker for PCS. cfDNA is a proven, useful marker of a variety of acute pathological conditions such as trauma and acute illness. METHODS Thirty mTBI patients were recruited for this prospective single-center trial. At admission, patients completed questionnaires and blood was drawn to obtain cfDNA. At 3–4 months after injury, 18 patients returned for cognitive assessments with questionnaires and the Color Trails Test (CTT). The fast SYBR Gold assay was used to measure cfDNA. RESULTS Seventeen men and 13 women participated in this trial. The mean ± SD age was 50.9 ± 13.9 years. Of the 18 patients who returned for cognitive assessment, one-third reported working fewer hours, 4 (22.2%) changed their driving patterns, and 5 (27.7%) reduced or stopped performing physical activity. The median cfDNA level of the mTBI group was greater than that of the matched healthy control group (730.5 vs 521.5 ng/ml, p = 0.0395). Admission cfDNA concentration was negatively correlated with performance on the CTT1 and CTT2 standardized tests (r = −0.559 and −0.599), meaning that greater cfDNA level was correlated with decreased cognitive performance status. The performance of the patients with normal cfDNA level included in the mTBI group was similar to that of the healthy participants. In contrast, the increased cfDNA group (> 800 ng/ml) had lower scores on the CTT tests than the normal cfDNA group (p < 0.001). Furthermore, patients with moderate/severe cognitive impairment according to CTT1 results had a greater median cfDNA level than the patients with scores indicating mild impairment or normal function (1186 vs 473.5 ng/ml, p = 0.0441, area under the receiver operating characteristic curve = 0.8393). CONCLUSIONS The data from this pilot study show the potential to use cfDNA, as measured with a fast test, as a biomarker to screen for PCS in the ER. A large-scale study is required to establish the value of cfDNA as an early predictor of PCS.

Cell-Free DNA Screening for Fetal Aneuploidy

2021 ◽  
pp. 115-120
Author(s):  
Ashley N. Battarbee ◽  
Neeta L. Vora
Keyword(s):  
Trisomy 21 ◽  
Dna Analysis ◽  
Chromosomal Abnormalities ◽  
Area Under The Curve ◽  
First Trimester ◽  
Outcome Data ◽  
Cell Free Dna ◽  
High Risk Women ◽  
Free Dna ◽  
Trimester Screening

In a prospective, multicenter blinded study at 35 international centers, the Noninvasive Examination of Trisomy (NEXT) study evaluated the performance of cell-free DNA screening for fetal trisomy compared to standard first trimester screening with nuchal translucency and serum analytes in a routine prenatal population. Among the 15,841 women who had standard screening and cell-free DNA analysis with neonatal outcome data, there were 68 chromosomal abnormalities (1 in 236). Of these, 38 were Trisomy 21 (1 in 417). Cell-free DNA analysis had a higher area under the curve (AUC) for trisomy 21, compared to standard screening (0.999 vs. 0.958, p = 0.001). Cell-free DNA analysis also had greater sensitivity, specificity, and positive predictive value compared to standard screening for trisomy 21, 18, and 13. While cell-free DNA analysis cannot detect all chromosome abnormalities, it performed better than standard screening for detection of trisomies 21, 18, and 13 in a routine population including low- and high-risk women.

scholarly journals Comparative Analysis of Urine Fractions for Optimal Bladder Cancer Detection Using DNA Methylation Markers

Cancers ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 859 ◽  
Author(s):  
Anouk E. Hentschel ◽  
Jakko A. Nieuwenhuijzen ◽  
Judith Bosschieter ◽  
Annina P. van Splunter ◽  
Birgit I. Lissenberg-Witte ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Bladder Cancer ◽  
Comparative Analysis ◽  
Area Under The Curve ◽  
Practical Reasons ◽  
Methylation Analysis ◽  
Cell Free Dna ◽  
Molecular Tests ◽  
Free Dna ◽  
Tumor Tissues

DNA methylation analysis of full void urine and urine pellet seems promising for bladder cancer (BC) detection and surveillance. Urinary cell-free DNA from urine supernatant is now gaining interest for other molecular tests in BC. This study aims to evaluate which urine fraction is preferred for BC diagnosis using methylation markers: full void urine, urine pellet or supernatant. Methylation levels of nine markers were determined in the three urine fractions and correlated with their respective tumor tissues in BC patients and compared to controls. For all markers and marker panel GHSR/MAL, diagnostic performance was determined by calculating the area under the curve (AUC) of the respective receiver operating characteristic curves. For most of the markers, there was a significant correlation between the methylation levels in each of the urine fractions and the matched tumor tissues. Urine pellet was the most representative fraction. Generally, AUCs for BC diagnosis were comparable among the fractions. The highest AUC was obtained for GHSR/MAL in urine pellet: AUC 0.87 (95% confidence interval: 0.73–1.00), corresponding to a sensitivity of 78.6% and a specificity of 91.7%. Our results demonstrate that cellular and cell-free DNA in urine can be used for BC diagnosis by urinary methylation analysis. Based on our comparative analysis and for practical reasons, we recommend the use of urine pellet.

scholarly journals Early clinical experience using donor‐derived cell‐free DNA to detect rejection in kidney transplant recipients

2019 ◽  
Vol 19 (6) ◽  
pp. 1663-1670 ◽  
Author(s):  
Edmund Huang ◽  
Supreet Sethi ◽  
Alice Peng ◽  
Reiad Najjar ◽  
James Mirocha ◽  
...  
Keyword(s):  
Kidney Transplant ◽  
Clinical Experience ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients ◽  
Cell Free Dna ◽  
Early Clinical Experience ◽  
Free Dna

scholarly journals A cell-free DNA metagenomic sequencing assay that integrates the damage response to infection

2019 ◽  
Author(s):  
Alexandre Pellan Cheng ◽  
Philip Burnham ◽  
John Richard Lee ◽  
Matthew Pellan Cheng ◽  
Manikkam Suthanthiran ◽  
...  
Keyword(s):  
Urinary Tract ◽  
High Throughput ◽  
High Throughput Sequencing ◽  
Viral Infections ◽  
Clinical Samples ◽  
Metagenomic Sequencing ◽  
Kidney Transplant Recipients ◽  
Bladder Tissue ◽  
Cell Free Dna ◽  
Free Dna

ABSTRACTHigh-throughput metagenomic sequencing offers an unbiased approach to identify pathogens in clinical samples. Conventional metagenomic sequencing however does not integrate information about the host, which is often critical to distinguish infection from infectious disease, and to assess the severity of disease. Here, we explore the utility of high-throughput sequencing of cell-free DNA after bisulfite conversion to map the tissue and cell types of origin of host-derived cell-free DNA, and to profile the bacterial and viral metagenome. We applied this assay to 51 urinary cfDNA isolates collected from a cohort of kidney transplant recipients with and without bacterial and viral infection of the urinary tract. We find that the cell and tissue types of origin of urinary cell-free DNA can be derived from its genome-wide profile of methylation marks, and strongly depend on infection status. We find evidence of kidney and bladder tissue damage due to viral and bacterial infection, respectively, and of the recruitment of neutrophils to the urinary tract during infection. Through direct comparison to conventional metagenomic sequencing as well as clinical tests of infection, we find this assay accurately captures the bacterial and viral composition of the sample. The assay presented here is straightforward to implement, offers a systems view into bacterial and viral infections of the urinary tract, and can find future use as a tool for the differential diagnosis of infections.

scholarly journals URINE DONOR DERIVED CELL FREE DNA AIDS IN THE DIAGNOSIS OF BK POLYOMAVIRUS NEPHROPATHY IN KIDNEY TRANSPLANT RECIPIENTS WITH BK VIRURIA

2020 ◽  
Vol 104 (S3) ◽  
pp. S367-S368
Author(s):  
Gang Huang ◽  
Xu-Tao Chen ◽  
Wen-Fang Chen ◽  
Pei-Song Chen ◽  
Ting-Ya Jiang ◽  
...  
Keyword(s):  
Kidney Transplant ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients ◽  
Cell Free Dna ◽  
Free Dna ◽  
Bk Polyomavirus ◽  
Urine Donor
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