scholarly journals The Use of Donor-Derived Cell-Free DNA for Assessment of Allograft Rejection and Injury Status

2020 ◽  
Vol 9 (5) ◽  
pp. 1480 ◽  
Author(s):  
Charat Thongprayoon ◽  
Pradeep Vaitla ◽  
Iasmina M. Craici ◽  
Napat Leeaphorn ◽  
Panupong Hansrivijit ◽  
...  
Keyword(s):  
Serum Creatinine ◽  
Allograft Rejection ◽  
Surrogate Marker ◽  
Diagnostic Tools ◽  
Cell Free Dna ◽  
Antibody Mediated Rejection ◽  
Acute Renal Allograft Rejection ◽  
Free Dna ◽  
Allograft Loss ◽  
Injury Status

Patient monitoring after kidney transplantation (KT) for early detection of allograft rejection remains key in preventing allograft loss. Serum creatinine has poor predictive value to detect ongoing active rejection as its increase is not sensitive, nor specific for acute renal allograft rejection. Diagnosis of acute rejection requires allograft biopsy and histological assessment, which can be logistically challenging in some cases and carries inherent risk for complications related to procedure. Donor-derived cell-free DNA (dd-cfDNA), DNA of donor origin in the blood of KT recipient arising from cells undergoing injury and death, has been examined as a potential surrogate marker for allograft rejection. A rise in dd-cfDNA levels precedes changes in serum creatinine allows early detections and use as a screening tool for allograft rejection. In addition, when used in conjunction with donor-specific antibodies (DSA), it increases the pre-biopsy probability of antibody-mediated rejection (ABMR) aiding the decision-making process. Advancements in noninvasive biomarker assays such as dd-cfDNA may offer the opportunity to improve and expand the spectrum of available diagnostic tools to monitor and detect risk for rejection and positively impact outcomes for KT recipients. In this this article, we discussed the evolution of dd-cfDNA assays and recent evidence of assessment of allograft rejection and injury status of KT by the use of dd-cfDNA.

scholarly journals Donor-Derived Cell-Free DNA (ddcf-DNA) and Acute Antibody-Mediated Rejection in Kidney Transplantation

Medicina ◽  
2021 ◽  
Vol 57 (5) ◽  
pp. 436
Author(s):  
Vishal Jaikaransingh ◽  
Pradeep V. Kadambi
Keyword(s):  
Kidney Transplantation ◽  
Allograft Rejection ◽  
Clinical Decision Making ◽  
Graft Loss ◽  
Clinical Decision ◽  
Kidney Transplant Recipients ◽  
Cell Free Dna ◽  
Antibody Mediated Rejection ◽  
Free Dna

Monitoring kidney transplant recipients for evidence of allograft rejection is essential to lower the risk of graft loss. The traditional method relies on serial checks in serum creatinine with a biopsy of the allograft if dysfunction is suspected. This is invasive, labor-intensive and costly. As such, there is widespread interest in the use of biomarkers to provide a noninvasive approach to detecting allograft rejection. One such biomarker is donor-derived cell-free DNA (ddcf-DNA). Here, we review the methodology for the determination of the amount/fraction of ddcf-DNA, evaluate the available data of its use in kidney transplantation and render an opinion in the clinical decision-making of these patients.

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 Value of Quantitative and Qualitative Analyses of Circulating Cell-Free DNA as Diagnostic Tools for Hepatocellular Carcinoma

Medicine ◽  
2015 ◽  
Vol 94 (14) ◽  
pp. e722 ◽  
Author(s):  
Wenjun Liao ◽  
Yilei Mao ◽  
Penglei Ge ◽  
Huayu Yang ◽  
Haifeng Xu ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Diagnostic Tools ◽  
Cell Free Dna ◽  
Free Dna ◽  
Qualitative Analyses ◽  
Circulating Cell Free Dna

scholarly journals Using Both the Fraction and Quantity of Donor-Derived Cell-Free DNA to Detect Kidney Allograft Rejection

2021 ◽  
pp. ASN.2021050645
Author(s):  
Suphamai Bunnapradist ◽  
Piyavadee Homkrailas ◽  
Ebad Ahmed ◽  
Gordon Fehringer ◽  
Paul Billings ◽  
...  
Keyword(s):  
Allograft Rejection ◽  
Cell Free Dna ◽  
Kidney Allograft ◽  
Free Dna ◽  
Kidney Allograft Rejection

Cell-free DNA as a surrogate marker in patients with CRPCA undergoing taxane-based chemotherapy.

2017 ◽  
Vol 35 (6_suppl) ◽  
pp. e584-e584 ◽  
Author(s):  
Friederike Haidl ◽  
Alexandra Kienel ◽  
David Pfister ◽  
Axel Heidenreich
Keyword(s):  
Lymph Node ◽  
Bone Metastasis ◽  
Lymph Node Metastasis ◽  
Specific Antigen ◽  
Surrogate Marker ◽  
Castration Resistant Prostate Cancer ◽  
Cell Free Dna ◽  
Node Metastasis ◽  
Free Dna ◽  
Median Serum

e584 Background: Taxane-based chemotherapy is one of the first-line life prolonging therapeutic approaches in metastatic castration-resistant prostate cancer (mCRPCA). Until now, there is no valid surrogate marker directly reflecting therapeutic response. Prostate specific antigen (PSA) and imaging studies are used to monitor therapy. The aim of this study was to assess whether circulating cell-free DNA (cfDNA) is suitable as a predictive and prognostic marker. Methods: cfDNA was isolated in 74 patients with mCRPCA receiving taxane based chemotherapy. Median serum cfDNA - concentration was correlated with localization of metastasis and tumor burden (bone, lymph node and visceral). In addition we examined the change of cfDNA - concentration under treatment. The median serum cfDNA - concentration at the time of 1st, 5th and 10th cycle of chemotherapy was correlated with PSA response (>80%, >50%, <30% decrease). Results: We identified 21 patients with a PSA decrease >80%, 41 patients with a PSA decrease >50%, 12 patients with a PSA decrease <30 % and 15 patients with a PSA rise during treatment. Median cfDNA concentration in patients with a PSA decrease of >80% was 34.96 ng/ml, in patients with a PSA decrease > 50% 34.96 ng/ml and in patients with a PSA decrease < 30% 38.475 ng/ml. The Median cfDNA concentration in patients with a PSA rise was 31.25 ng/ml. Median cfDNA concentration in patients with lymph node metastasis was 33.78 ng/ml, with bone metastasis < 3 34.24 ng/ml, bone metastasis >3 31.97 ng/ml and with visceral metastasis 34.57 ng/ml. There was no significant correlation between median cfDNA - concentration and type of metastasis (cfDNA vs. PSA bone metastasis <3, P = 0,56938, cfDNA vs. PSA bone metastasis >3 P = 0.472, cfDNA vs. PSA lymph node metastasis P = 0.423). There was no significant change of median cfDNA concentration under treatment ( P > 0.05). Conclusions: Although cfDNA-concentration is a prognostic and predictive marker for survival and therapy response as shown recently, our findings suggest that cfDNA as a surrogate marker is unsuitable.

scholarly journals Prospective evaluation of donor-derived cell-free DNA as a potential biomarker for cardiac allograft vasculopathy

2021 ◽  
Vol 42 (Supplement_1) ◽  
Author(s):  
M Jimenez-Blanco Bravo ◽  
L Perez Gomez ◽  
C Arellano Serrano ◽  
F.J Hernandez Perez ◽  
M Gomez Bueno ◽  
...  
Keyword(s):  
Unmet Need ◽  
Cardiac Allograft Vasculopathy ◽  
Cardiac Allograft ◽  
Allograft Vasculopathy ◽  
Cell Free Dna ◽  
Antibody Mediated Rejection ◽  
Free Dna ◽  
Asymptomatic Patients ◽  
Potential Biomarker ◽  
Coronary Angiograms

Abstract Background Cardiac allograft vasculopathy (CAV) remains a major cause of morbidity and mortality among long-term heart transplant (HT) recipients. There is clearly an unmet need for a noninvasive biomarker of CAV that could obviate the need to perform surveillance coronary angiograms in these patients. Purpose Our aim was to evaluate the performance of Donor-derived Cell Free DNA (dd-cfDNA) as a biomarker of CAV. Methods We prospectively measured dd-cfDNA levels in all consecutive asymptomatic patients undergoing surveillance coronary angiography &gt;1 year after HT at a single center, between Jan 2019 and Jan 2021. Endpoints included the association between dd-cfDNA levels and the presence CAV, according to ISHLT 2010 classification. Patients with history of acute cellular rejection ≥1R or antibody mediated rejection in the previous 6 months were excluded. Results We included 94 HT recipients, median age 57 years (IQR 50–67), 67% men, a median of 10.9 years after transplant. Coronary angiogram revealed CAV0, CAV1, CAV2 and CAV3 in 61%, 19%, 14% and 6% of patients, respectively. Median dd-cfDNA values for each CAV group were: CAV0 0.92% (IQR 0.46–2.0), CAV1 1.4% (0.38–2.8), CAV2 0.17% (0.07–0.52) and CAV3 0.24% (0.057–0.87); p=0.0535. Figure 1 summarizes baseline characteristics of the cohort and results. Comparison of dd-cfDNA levels in patients with CAV0 and CAV1–2-3 did not show significant differences (0.92%, IQR 0.46–2.0 vs 0.46%, IQR 0.075–1.5, p=0.059) (Figure 2A), nor did the comparison between patients with stable CAV (no new coronary lesions since previous angiogram, n=77) and progressive CAV (patients with new coronary stenoses, n=17); median dd-cfDNA values were 0.735% (IQR 0.195–2.0) vs 0.9% (IQR 0.12–1.8), p=0.76 (Figure 2B). A subanalysis according to time after HT was also found non-significant: less than 5 years (p=0.95), 5 to 10 years (p=0.14) and more than 10 years after HT (p=0.16) (Figure 2C). The AUC ROC curve for the diagnosis of CAV revealed the lack of ability to predict the presence of any degree of CAV (AUC ROC = 0.38). Conclusion In our experience, dd-cfDNA did not perform as a useful biomarker to avoid surveillance coronary angiograms for CAV diagnosis. FUNDunding Acknowledgement Type of funding sources: Other. Main funding source(s): Sociedad Madrileña de Trasplantes

The Role of Donor-Derived Cell-Free DNA in the Identification of Injury in Kidney Allografts with Antibody-Mediated Rejection or De Novo DSA

2018 ◽  
Vol 102 ◽  
pp. S5-S6
Author(s):  
Huanxi Zhang ◽  
Longshan Liu ◽  
Chunting Zheng ◽  
Xirui Li ◽  
Qian Fu ◽  
...  
Keyword(s):  
De Novo ◽  
Cell Free Dna ◽  
Antibody Mediated Rejection ◽  
Free Dna
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