An Assessment of the Value of Donor-derived Cell-free DNA Surveillance in Patients With Preserved Kidney Allograft Function

Huang, Edmund; Haas, Mark; Gillespie, Matt; Sethi, Supreet; Peng, Alice; Najjar, Reiad; Vo, Ashley; Jordan, Stanley C.

doi:10.1097/tp.0000000000004267

Cited by 12 publications

(10 citation statements)

References 21 publications

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“…As shown with the synthetic oversampling approach in Table 5 , PPV can be improved by increasing the disease prevalence. PPV values were shown to be increased by using additional tests, such as a combination of dd-cfDNA and blood transcriptomics, 8 , 10 by increasing the threshold of dd-cfDNA 4 , 23 or gene transcripts, 11 or by addition of DSA. 4 , 23 - 25 PPV increased to 0.81 when both TruGraf and dd-ccDNA (TRAC) were positive.…”

Section: Discussionmentioning

confidence: 99%

Performance and Advancement of the Kidney Solid Organ Response Test

Lee,

Barbachan e Silva,

Bao

et al. 2023

Transplantation

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Background. The kidney solid organ response test (kSORT) has been investigated for the prediction of acute rejection in kidney transplant recipients with conflicting results. We aimed to investigate if the kSORT assay score is associated with rejection or immune quiescence. Methods. The blinded association between rejection and kSORT > 9 were investigated. Optimization of kSORT prediction was evaluated after unblinding to determine the optimal prediction cutoff value of kSORT score. Additionally, the predictive capability of the kSORT gene set was assessed using blinded normalized gene expression data from microarray (Affymetrix) and qPCR assays. Results. Of the 95 blood samples analyzed, 18 patients had blood samples before transplant, 77 patients after transplant and 71 had clinically indicated biopsies of which 15 biopsies showed acute rejection and 16 showed chronic active antibody-mediated rejection. When 31 patients with rejection were compared to the remaining 64 patients, positive predictive value (PPV) was 54.29% and negative predictive value (NPV) was 75% when stratified using a kSORT score > 9, and PPV was 57.89% and NPV was 78.95% when stratified using a kSORT score > 5. Using the kSORT assay for detection of rejection showed an area under the curve value of 0.71. Microarray data improved prediction accuracy with PPV of 53% and NPV of 84% compared to qPCR results (PPV and NPV were 36% and 66%), respectively. Conclusions. The kSORT assay has the potential to be used as a predictive tool for active rejection and/or immune quiescence, but additional studies will be useful in improving and refining the kSORT assay, in particular the prediction algorithm.

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Section: Discussionmentioning

confidence: 99%

Performance and Advancement of the Kidney Solid Organ Response Test

Lee,

Barbachan e Silva,

Bao

et al. 2023

Transplantation

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“…To address this, a subsequent retrospective observational single-center study focused on dd-cfDNA surveillance in stable patients with normal allograft function (i.e., creatinine less than 1.5 mg/dL; absence of DSAs; and no history of clinical rejection) over a median follow-up period of 1.5 years. 58 Although elevated dd-cfDNA was a predictor of rejection, most patients with elevated dd-cfDNA remained clinically stable. The utility of cfDNA monitoring alone in the setting of stable allograft function remains unclear.…”

Section: Key Findingsmentioning

confidence: 98%

Updates in Kidney Transplantation From the 2022 Banff-Canadian Society of Transplantation Joint Meeting: Conference Report

Carrigan,

Mathur,

Bourgeois

et al. 2023

Can J Kidney Health Dis

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Purpose of the Conference: The 2022 Banff-Canadian Society of Transplantation Meeting in Banff, Alberta, brought together transplant professionals to review new developments across various aspects of solid organ transplantation (SOT) in Canada. Sources of Information: Presentations included consensus recommendations from expert-led forums; experiences with new procedures and legislation; reports from public health data repositories; original clinical and laboratory research; and industry updates regarding novel technologies. Speakers referenced articles and reports published in peer-reviewed journals and online, and unpublished data and preliminary findings. Methods: All authors attended presentations in-person or virtually. Recordings of select presentations were available for later review. Summaries emphasize concepts indicated by speakers as new and clinically relevant. Key Findings: The COVID-19 pandemic disproportionately affected solid organ transplant recipients (SOTRs), who experience worse outcomes of COVID-19 infection than the general population. Vaccinations demonstrate an attenuated immunological response in SOTRs yet provide meaningful protection. Monoclonal antibodies are effective for both passive immunization and treatment of COVID-19 in SOTRs. Infection control protocols have driven the development of virtual methods for clinical research, such as using home blood draws and virtual follow-up to evaluate vaccine efficacy in SOTRs; and patient care delivery, such as employing telerehabilitation post transplant. Access to living kidney donation is limited by various disincentives experienced by potential donors, which may be overcome by more efficient evaluations including a One-Day Living Kidney Donor Assessment Clinic. The International Donation and Transplantation Legislative and Policy Forum provided a means of establishing consensus guidance for organ donation and transplantation (ODT) program policy to standardize delivery across jurisdictions. The implementation of a deemed consent model for organ and tissue donation in Nova Scotia may provide insight as to whether this model indeed improves access to organs. Canada’s Indigenous population experiences unique barriers to transplantation, prompting efforts for more inclusive ODT policy-making. The Pan-Canadian ODT Data and Performance Reporting System Project has defined performance quality indicators, of which iTransplant and other point-of-care software solutions may facilitate collection; however, these endeavors ultimately require information technology infrastructure that exceeds the capabilities of the existing Canadian Organ Replacement Register and Canadian Transplant Registry. Pig-to-human xenotransplantation requires genetic modification of pigs and xenoantibody testing in recipients but may yet prove viable. Serum cell-free DNA, urine biomarkers, and genetic markers offer an alternative to routine biopsy for identifying subclinical rejection. Modified perfusion temperatures and perfusion solutions with hydrogen sulfide donor compounds may improve organ preservation. Molecular compatibility tools provide another means of improving SOTR outcomes, and the Genome Canada Transplant Consortium has been examining important considerations of their implementation. Limitations: We were unable to capture all presentations and topics at the meeting due to the sizable quantity and variety. Topics ultimately excluded from this summary include those in pathology including Banff Classification updates; those unique to extra-renal SOT; as well as numerous abstract and poster presentations, allied health provider forums, and business meetings. A portion of the material was presented by speakers prior to peer-review or publication. Implications: The various conference presentations summarized in this report identify methods by which individual clinicians and provincial ODT programs may improve access, delivery, and quality of SOT care in Canada, while additionally identifying gaps in the literature that investigators are encouraged to pursue.

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“…Studies of dd-cfDNA outside of these initial trials have led to variable outcomes and an overall lack of consensus regarding the most appropriate application of the test. While studies have generalized that patients with higher dd-cfDNA experience higher rates of rejection, the ability to accurately predict adverse events among these patients is still lacking (97). This is because dd-cfDNA is elevated in a multitude of pathologies and lacks the ability to distinguish among infectious or immunologic etiologies of graft injury (98).…”

Section: Ready For Prime Timementioning

confidence: 99%

Progress in kidney transplantation: The role for systems immunology

et al. 2022

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The development of systems biology represents an immense breakthrough in our ability to perform translational research and deliver personalized and precision medicine. A multidisciplinary approach in combination with use of novel techniques allows for the extraction and analysis of vast quantities of data even from the volume and source limited samples that can be obtained from human subjects. Continued advances in microfluidics, scalability and affordability of sequencing technologies, and development of data analysis tools have made the application of a multi-omics, or systems, approach more accessible for use outside of specialized centers. The study of alloimmune and protective immune responses after solid organ transplant offers innumerable opportunities for a multi-omics approach, however, transplant immunology labs are only just beginning to adopt the systems methodology. In this review, we focus on advances in biological techniques and how they are improving our understanding of the immune system and its interactions, highlighting potential applications in transplant immunology. First, we describe the techniques that are available, with emphasis on major advances that allow for increased scalability. Then, we review initial applications in the field of transplantation with a focus on topics that are nearing clinical integration. Finally, we examine major barriers to adapting these methods and discuss potential future developments.

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An Assessment of the Value of Donor-derived Cell-free DNA Surveillance in Patients With Preserved Kidney Allograft Function

Cited by 12 publications

References 21 publications

Performance and Advancement of the Kidney Solid Organ Response Test

Performance and Advancement of the Kidney Solid Organ Response Test

Updates in Kidney Transplantation From the 2022 Banff-Canadian Society of Transplantation Joint Meeting: Conference Report

Progress in kidney transplantation: The role for systems immunology

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