A Novel, High Throughput Droplet Digital PCR-Based Indel Quantification Method for the Detection of Circulating Donor-Derived Cell-Free DNA After Kidney Transplantation

J. G. Verhoeven¹, K. Boer¹, A. M. Peeters¹, M. C. Clahsen-van Groningen², J. I. Roodnat¹, J. van de Wetering¹, D. Nieboer³, D. A. Bost⁴, C. C. Baan¹, D. A. Hesselink¹

¹Department of Internal Medicine, Erasmus MC Transplant Institute, Rotterdam, Netherlands, ²Department of Pathology, University Medical Center Rotterdam, Rotterdam, Netherlands, ³Department of Public Health, University Medical Center Rotterdam, Rotterdam, Netherlands, ⁴JETA Molecular, Utrecht, Netherlands

Meeting: 2022 American Transplant Congress

Abstract number: 1561

Keywords: Kidney, Monitoring, Rejection

Topic: Basic Science » Basic Clinical Science » 17 - Biomarkers: Clinical Outcomes

Session Information

Session Name: Biomarkers: Clinical Outcomes

Session Type: Poster Abstract

Date: Tuesday, June 7, 2022

Session Time: 7:00pm-8:00pm

Presentation Time: 7:00pm-8:00pm

Location: Hynes Halls C & D

*Purpose: Donor-derived cell-free DNA (ddcfDNA) is a promising minimally invasive biomarker for acute rejection (AR) in kidney transplant recipients. To assess the diagnostic value of ddcfDNA as marker for AR, ddcfDNA was quantified at multiple time points after kidney transplantation with a novel high-throughput droplet digital PCR (ddPCR) indel method that allowed for the absolute quantification of ddcfDNA.

*Methods: In this study, ddcfDNA in plasma samples from 223 consecutive kidney transplant recipients was analyzed pre-transplantation, and at 3, 7 and 180 days after transplantation, and at time of for-cause biopsies obtained within the first 180 days after transplantation.

*Results: Median (interquartile range [IQR]) ddcfDNA concentration was significantly higher on day 3 (58.3 [17.7-258.3] copies/mL) and day 7 (25.0 [10.4-70.8] copies/mL) compared to day 180 after transplantation (4.2 [0.0-8.3] copies/mL; p&lt0.001 and p&lt0.001, respectively). At time of biopsy-proven AR (BPAR), between day 11 and 180 after transplantation, ddcfDNA concentration was significantly higher (50.0 [25.0-108.3] copies/mL) compared to those when biopsies showed non-AR (0.0 [0.0-15.6] copies/mL; p&lt0.05). ddcfDNA concentration within the first 10 days after transplantation showed no significant difference between recipients with BPAR and those with non-AR in their biopsy or between recipients with BPAR and ddcfDNA measured at day 3 and day 7.

*Conclusions: Unfortunately, ddcfDNA concentration is not a good biomarker to detect AR within the first 10 days after transplantation. However, BPAR occurring after 10 days after transplantation can be detected in kidney transplant recipients by ddcfDNA using a novel and unique, high-throughput ddPCR indel method.

To cite this abstract in AMA style:

Verhoeven JG, Boer K, Peeters AM, Groningen MCClahsen-van, Roodnat JI, Wetering Jvande, Nieboer D, Bost DA, Baan CC, Hesselink DA. A Novel, High Throughput Droplet Digital PCR-Based Indel Quantification Method for the Detection of Circulating Donor-Derived Cell-Free DNA After Kidney Transplantation [abstract]. Am J Transplant. 2022; 22 (suppl 3). https://atcmeetingabstracts.com/abstract/a-novel-high-throughput-droplet-digital-pcr-based-indel-quantification-method-for-the-detection-of-circulating-donor-derived-cell-free-dna-after-kidney-transplantation/. Accessed December 3, 2024.

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