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Randomized clinical trial of a novel donor-derived cfDNA test to detect rejection in CPV-simulated renal transplant patients

  • Nephrology - Original Paper
  • Published:
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Abstract

Purpose

Five-year kidney graft loss currently stands at about 30%. We evaluate the clinical utility of a blood test measuring donor-derived cell-free DNA that detects rejection earlier and, potentially, improves diagnostic and therapeutic accuracy.

Methods

In a randomized controlled experiment, we measured the clinical practice of 175 practicing nephrologists, both with and without the use of dd-cfDNA testing. Providers cared for six simulated post-renal transplant patient cases whose ages ranged from 30 to 75 years and were 3–24 months post-transplant with typical presentations.

Results

154 nephrologists completed two rounds of simulated cases. At baseline, the study arms performed similarly, demonstrating no significant differences either in primary diagnosis (p = 0.853), decisions to biopsy or refer to transplant center (p = 1.000), or therapeutic management (p = 0.488). After introduction of the dd-cfDNA test, intervention nephrologists were more likely to arrive at the diagnosis of rejection (OR 4.00, 95% CI 1.93–8.30), make a correct decision on biopsy/transplant center referral (OR 11.07, 95% CI 4.87–25.16), and properly adjust therapeutic management (OR 2.37, 95% CI 1.07–5.24).

Conclusion

A sample of nationally representative, practicing nephrologists given dd-cfDNA to evaluate post-transplant patients were more likely to correctly diagnose early and subclinical allograft rejection, to send for biopsy or refer to transplant center, and to appropriately change treatment than those nephrologists without dd-cfDNA access.

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Abbreviations

CPV:

Clinical performance and value

dd-cfDNA:

Donor-derived cell-free DNA

mmPCR:

Massively multiplexed polymerase chain reaction

NGS:

Next-generation sequencing

SNP:

Single nucleotide polymorphisms

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Funding

This study was funded by Natera, Inc., San Carlos, California.

Author information

Authors and Affiliations

  1. School of Medicine, University of California, 450 Pacific Ave, Suite 200, San Francisco, CA, 94133, USA

    John Peabody

  2. Fielding School of Public Health, University of California, Los Angeles, USA

    John Peabody

  3. QURE Healthcare, San Francisco, CA, USA

    John Peabody, Czarlota Valdenor, Mary Tran & David Paculdo

  4. Natera, Inc, San Carlos, CA, USA

    Paul Billings, Zach Demko & Solomon Moshkevich

Authors
  1. John Peabody
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  2. Paul Billings
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  3. Czarlota Valdenor
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  4. Zach Demko
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  5. Solomon Moshkevich
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  6. Mary Tran
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  7. David Paculdo
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Corresponding author

Correspondence to John Peabody.

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Conflict of interest

QURE, LLC, was contracted by Natera, Inc., to perform the study. PB, ZD, and SM are employees of Natera, Inc. JP, CV, MT, and DP are employees of QURE, LLC.

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Peabody, J., Billings, P., Valdenor, C. et al. Randomized clinical trial of a novel donor-derived cfDNA test to detect rejection in CPV-simulated renal transplant patients. Int Urol Nephrol 52, 1593–1601 (2020). https://doi.org/10.1007/s11255-020-02491-1

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  • DOI: https://doi.org/10.1007/s11255-020-02491-1

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