scholarly journals Donor-Derived Cell-Free DNA in Kidney Transplantation: Origins, Present and a Look to the Future

Medicina ◽  
2021 ◽  
Vol 57 (5) ◽  
pp. 482
Author(s):  
Sam Kant ◽  
Daniel C. Brennan
Keyword(s):  
Kidney Transplantation ◽  
Organ Transplantation ◽  
Allograft Rejection ◽  
Solid Organ Transplantation ◽  
Solid Organ ◽  
Future Prospects ◽  
Cell Free Dna ◽  
Medical Specialties ◽  
Free Dna ◽  
The Future

Since its first detection in 1948, donor-derived cell-free DNA (dd-cfDNA) has been employed for a myriad of indications in various medical specialties. It has had a far-reaching impact in solid organ transplantation, with the most widespread utilization in kidney transplantation for the surveillance and detection of allograft rejection. The purpose of this review is to track the arc of this revolutionary test—from origins to current use—along with examining challenges and future prospects though the lens of transplant nephrology.

Donor-Derived Cell-Free DNA Is a Novel Universal Biomarker for Allograft Rejection in Solid Organ Transplantation

2015 ◽  
Vol 47 (8) ◽  
pp. 2400-2403 ◽  
Author(s):  
J. Beck ◽  
M. Oellerich ◽  
U. Schulz ◽  
V. Schauerte ◽  
L. Reinhard ◽  
...  
Keyword(s):  
Organ Transplantation ◽  
Allograft Rejection ◽  
Solid Organ Transplantation ◽  
Solid Organ ◽  
Cell Free Dna ◽  
Free Dna

scholarly journals Origin of Plasma Cell-free DNA after Solid Organ Transplantation

2003 ◽  
Vol 49 (3) ◽  
pp. 495-496 ◽  
Author(s):  
Yanni Y N Lui ◽  
Kam-Sang Woo ◽  
Angela Y M Wang ◽  
Chung-Kwong Yeung ◽  
Philip K T Li ◽  
...  
Keyword(s):  
Organ Transplantation ◽  
Plasma Cell ◽  
Solid Organ Transplantation ◽  
Solid Organ ◽  
Cell Free Dna ◽  
Free Dna

Donor-Derived Cell-Free DNA Testing in Solid Organ Transplantation: A Value Proposition

2020 ◽  
Vol 5 (5) ◽  
pp. 993-1004 ◽  
Author(s):  
Michael Oellerich ◽  
Robert H Christenson ◽  
Julia Beck ◽  
Ekkehard Schütz ◽  
Karen Sherwood ◽  
...  
Keyword(s):  
Organ Transplantation ◽  
Solid Organ Transplantation ◽  
Solid Organ ◽  
Value Proposition ◽  
Cell Free Dna ◽  
Long Term Outcome ◽  
Economic Implications ◽  
A Value ◽  
Free Dna ◽  
Protocol Biopsies

Abstract Background There is a need to improve personalized immunosuppression in organ transplantation to reduce premature graft loss. More efficient biomarkers are needed to better detect rejection, asymptomatic graft injury, and under-immunosuppression. Assessment of minimal necessary exposure to guide tapering and to prevent immune activation is also important. Donor-derived cell-free DNA (dd-cfDNA) has become available for comprehensive monitoring of allograft integrity. A value proposition concept was applied to assess the potential benefits of dd-cfDNA to stakeholders (patient, transplant physician, laboratory medicine specialist, hospital management, insurance companies) involved in solid organ transplantation care. Content There is robust clinical evidence from more than 48 published studies supporting the role of dd-cfDNA for monitoring graft integrity and detection or exclusion of rejection. The value proposition framework was used to evaluate published key evidence regarding clinical validity, economic implications, and limitations of this approach. It has been shown that dd-cfDNA testing is essential for guiding earlier transplant injury intervention with potential for improved long-term outcome. Summary Monitoring dd-cfDNA offers a rapid and reproducible method to detect graft injuries at an early actionable stage without protocol biopsies and allows for more effective personalized immunosuppression. The appropriate use of dd-cfDNA testing can provide both clinical and economic benefits to all transplantation stakeholders.

scholarly journals Probe-Free Digital PCR Quantitative Methodology to Measure Donor-Specific Cell-Free DNA after Solid-Organ Transplantation

2017 ◽  
Vol 63 (3) ◽  
pp. 742-750 ◽  
Author(s):  
Su Kah Goh ◽  
Vijayaragavan Muralidharan ◽  
Christopher Christophi ◽  
Hongdo Do ◽  
Alexander Dobrovic
Keyword(s):  
Organ Transplantation ◽  
Graft Rejection ◽  
Solid Organ Transplantation ◽  
Digital Pcr ◽  
Specific Cell ◽  
Solid Organ ◽  
Quantitative Methodology ◽  
Cell Free Dna ◽  
Free Dna ◽  
Specificity And Sensitivity

Abstract BACKGROUND Donor-specific cell-free DNA (dscfDNA) is increasingly being considered as a noninvasive biomarker to monitor graft health and diagnose graft rejection after solid-organ transplantation. However, current approaches used to measure dscfDNA can be costly and/or laborious. A probe-free droplet digital PCR (ddPCR) methodology using small deletion/insertion polymorphisms (DIPs) was developed to circumvent these limitations without compromising the quantification of dscfDNA. This method was called PHABRE-PCR (Primer to Hybridize across an Allelic BREakpoint-PCR). The strategic placement of one primer to hybridize across an allelic breakpoint ensured highly specific PCR amplification, which then enabled the absolute quantification of donor-specific alleles by probe-free ddPCR. METHODS dscfDNA was serially measured in 3 liver transplant recipients. Donor and recipient genomic DNA was first genotyped against a panel of DIPs to identify donor-specific alleles. Alleles that differentiated donor-specific from recipient-specific DNA were then selected to quantify dscfDNA in the recipient plasma. RESULTS Lack of amplification of nontargeted alleles confirmed that PHABRE-PCR was highly specific. In recipients who underwent transplantation, dscfDNA was increased at day 3, but decreased and plateaued at a low concentration by 2 weeks in the 2 recipients who did not develop any complications. In the third transplant recipient, a marked increase of dscfDNA coincided with an episode of graft rejection. CONCLUSIONS PHABRE-PCR was able to quantify dscfDNA with high analytical specificity and sensitivity. The implementation of a DIP-based approach permits surveillance of dscfDNA as a potential measure of graft health after solid-organ transplantation.

Treatment of Kaposi's sarcoma after solid organ transplantation.

1997 ◽  
Vol 15 (6) ◽  
pp. 2371-2377 ◽  
Author(s):  
F A Shepherd ◽  
E Maher ◽  
C Cardella ◽  
E Cole ◽  
P Greig ◽  
...  
Keyword(s):  
Kidney Transplantation ◽  
Organ Transplantation ◽  
Combination Chemotherapy ◽  
Kaposi's Sarcoma ◽  
Solid Organ Transplantation ◽  
Kaposi’S Sarcoma ◽  
Skin Toxicity ◽  
Solid Organ ◽  
Duration Of Response ◽  
Italian Origin

PURPOSE This retrospective review of all patients who developed Kaposi's sarcoma (KS) after solid organ transplantation at a single institution was undertaken to define the clinical presentation of this malignancy in the setting of iatrogenic immunodeficiency, and to determine the most appropriate treatment for patients in this clinical setting. MATERIALS AND METHODS The records of 2,099 patients who underwent heart, lung, liver, or kidney transplantation at The Toronto Hospital between January 1, 1981 and June 30, 1995, were reviewed. Twelve patients were identified who developed biopsy-proven KS in the posttransplantation period. Five patients who had disseminated KS who had not responded to either reduction or withdrawal of immunosuppression or to local radiotherapy were treated with combination chemotherapy consisting of doxorubicin 20 to 30 mg/m2, bleomycin 10 mg/m2, and vincristine 2 mg (ABV) administered intravenously every 3 weeks. RESULTS Eight of 12 patients were male and nine were of Italian origin. KS was limited to a localized area of the skin for only six patients, all after kidney transplantation. Visceral KS was present in three patients. Four of five patients responded to ABV chemotherapy (two complete and two partial remissions). The fifth patient responded to second-line etoposide and cisplatin. The median duration of response was in excess of 13 months (range, 8+ to 45+ months). Toxicity was limited to grade 1 neurotoxicity and grade 1 skin toxicity. CONCLUSION KS is an uncommon but recognized complication of solid organ transplantation. Combination chemotherapy is a safe and effective treatment for patients with disseminated or visceral KS that fails to respond to changes in immunosuppression.

Ethical issues in Kidney Transplantation and “An” Islamic perspective

2021 ◽  
Vol 20 (2) ◽  
pp. 241-249
Author(s):  
Mohammad Yousuf Rathor ◽  
Azarisman SM Shah ◽  
Nur Raziana Bt Rozi ◽  
Che Rosle Draman ◽  
Wan Ahmad Syahril
Keyword(s):  
Kidney Transplantation ◽  
Organ Donation ◽  
Organ Transplantation ◽  
Islamic Law ◽  
Ethical Issues ◽  
Human Life ◽  
Medical Science ◽  
Solid Organ Transplantation ◽  
Solid Organ ◽  
Living Kidney Donor

Kidney transplantation (KT) is currently the most realistic treatment option for patients with end-stage renal disease (ESRD) as it enables them to live longer and provides better quality of life post-transplantation. Before the 1960s, all these patients would die as there was no treatment available. It is the commonest solid organ transplantation carried out in the world at the moment. Organs are harvested from living or cadaveric donors, with living kidney donor organs generally functioning better and for longer periods of time compared to the latter. Issues surrounding organ transplantation in general and kidney transplantation in particular, are fraught with ethical dilemmas due to the shortage of organs, the logistics behind the acquisition of organs, use of living donors including minors and the black market that has sprouted thereof. Entwined in this quagmire are the legal, social and psychological consequences for the individuals involved and the society at large. It is further compounded by religious concerns, which have a significant influence on the society’s acceptance of the practice of organ donation. The practice of organ transplantation is generally accepted by most Islamic scholars as it is concordant to the objectives of Islamic Law (maqasid al Sharī’ah) which prioritize the preservation of human life. However, resistances do arise from some jurists and even physicians of the same Islamic faith despite a fatwas decreeing that organ and tissue transplantations are permissible in Islam under certain conditions. The take-up of organ-donation is still largely poor especially among Muslims. This article therefore hopes to explore the various moral and ethical issues surrounding KT as well as the Islamic viewpoints emanating from it. We hope that this knowledge and understanding will benefit both health-care personnel and the public in general. Bangladesh Journal of Medical Science Vol.20(2) 2021 p.241-249

Cell-free DNA and RNA - measurement and applications in clinical diagnostics with focus on metabolic disorders

2020 ◽  
Author(s):  
Markus Hodal Drag ◽  
Tuomas Oskari Kilpeläinen
Keyword(s):  
Metabolic Disorders ◽  
Solid Organ Transplantation ◽  
Prenatal Testing ◽  
Clinical Diagnostics ◽  
Solid Organ ◽  
Liquid Biopsies ◽  
Cell Free Dna ◽  
Alcoholic Fatty Liver ◽  
Non Invasive ◽  
Free Dna

Circulating cell-free DNA (cfDNA) and RNA (cfRNA) hold enormous potential as a new class of biomarkers for the development of non-invasive liquid biopsies in many diseases and conditions. In recent years, cfDNA and cfRNA have been studied intensely as tools for non-invasive prenatal testing, solid organ transplantation, cancer screening, and monitoring of tumors. In obesity, higher cfDNA concentration indicates accelerated cellular turnover of adipocytes during expansion of adipose mass and may be directly involved in the development of adipose tissue insulin resistance by inducing inflammation. Furthermore, cfDNA and cfRNA have promising diagnostic value in a range of obesity-related metabolic disorders, such as non-alcoholic fatty liver disease, type 2 diabetes, and diabetic complications. Here, we review the current and future applications of cfDNA and cfRNA within clinical diagnostics, discuss technical and analytical challenges in the field, and summarise the opportunities of using cfDNA and cfRNA in the diagnostics and prognostics of obesity-related metabolic disorders.

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