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



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.


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.


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).


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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Fig. 1



Clinical performance and value


Donor-derived cell-free DNA


Massively multiplexed polymerase chain reaction


Next-generation sequencing


Single nucleotide polymorphisms


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

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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).

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  • Allograft rejection
  • Renal transplant
  • Biopsy
  • Clinical practice
  • Donor-derived cell-free DNA