Authors’ Reply : Journal of the American Society of Nephrology

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Authors’ Reply

Bunnapradist, Suphamai1; Tabriziani, Hossein2

Author Information
JASN 32(11):p 2973-2974, November 2021. | DOI: 10.1681/ASN.2021081039
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We thank Drs. Gupta and Kaplan for their insightful comments. As we noted in our Research Letter, this preliminary report of the novel two-threshold algorithm had a small cohort size and limited confirmatory biopsy specimen data.1 We are currently in the process of applying this two-threshold algorithm to a larger cohort as part of a prospective, >30-site study with full biopsy matching. This study will contain more cases of biopsy specimen–proven acute rejection than the combined initial validation studies of the two clinically available donor-derived cell-free DNA (dd-cfDNA) fraction assays,2,3 addressing concerns of inadequate sample size.

We agree that the clinical utilization of diagnostic testing should be evidence driven. The two-threshold algorithm disclosed in our Research Letter did identify several rejections with elevated cfDNA and borderline dd-cfDNA results, and thus may be useful in patients with borderline dd-cfDNA fractions. As such, Natera intends to include both the dd-cfDNA fraction and the absolute dd-cfDNA quantity in our clinical reports. This will allow transplant physicians and surgeons to continue using the dd-cfDNA fraction cutoff as usual, while also having access to the two-threshold algorithm, which may prove valuable in key cases.

We are excited about the promise of biomarkers, especially dd-cfDNA, in kidney transplant surveillance, and agree that the implementation and interpretation of biomarker assays are best supported by solid clinical evidence.

Disclosures

S. Bunnapradist reports consultancy agreements with CareDx, Taekeda and Natera; research funding from Astellas, CareDx, Merck, Angion, Vitaeris and Natera, Angion; honoraria from BMS, Veloxis, Caredx, and Sanofi; and speakers bureau from Eurofins, TGI, Veloxis, Caredx, Natera, and Sanofi. H. Tabriziani reports current employment, consultancy agreements, ownership interest, scientific Advisor or membership, and speakers bureau with Natera; and other interests/relationships with HossMed, Inc.

Funding

None.

Published online ahead of print. Publication date available at www.jasn.org.

See related letter to the editor, “Need for a Validation Study before Using the Two-Step Algorithm for dd-cfDNA to Screen for Acute Rejection,” on pages and research letter, “Using both the Fraction and Quantity of Donor-Derived Cell-Free DNA to Detect Kidney Allograft Rejection,” in Vol. 32, Iss. 10, on pages .

References

1. Bunnapradist S, Homkrailas P, Ahmed E, Fehringer G, Billings P, Tabriziani H: Using both the fraction and quantity of donor-derived cell-free DNA to detect kidney allograft rejection. J Am Soc Nephrol 32: 2439–2441, 2021
2. Bloom RD, Bromberg JS, Poggio ED, Bunnapradist S, Langone AJ, Sood P, et al.; Circulating Donor-Derived Cell-Free DNA in Blood for Diagnosing Active Rejection in Kidney Transplant Recipients (DART) Study Investigators: Cell-free DNA and active rejection in kidney allografts. J Am Soc Nephrol 32: 2221–2232, 2017
3. Sigdel TK, Archila FA, Constantin T, Prins SA, Liberto J, Damm I, et al.: Optimizing detection of kidney transplant injury by assessment of donor-derived cell-free DNA via massively multiplex PCR. J Clin Med 32: 19, 2018
Keywords:

acute rejection; acute allograft rejection; chronic allograft rejection; kidney; kidney biopsy; transplantation

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