Donor-Derived Cell-Free DNA Outperforms Serum Creatinine Changes for Identifying Kidney Transplant Rejection
1University of Maryland School of Medicine, Baltimore, MD
2CareDx, Brisbane, CA
3University of Minnesota School of Medicine, Minneapolis, MN.
Meeting: 2018 American Transplant Congress
Abstract number: A90
Keywords: Kidney transplantation, Rejection
Session Information
Session Name: Poster Session A: Kidney Acute Antibody Mediated Rejection
Session Type: Poster Session
Date: Saturday, June 2, 2018
Session Time: 5:30pm-7:30pm
Presentation Time: 5:30pm-7:30pm
Location: Hall 4EF
Purpose: In the DART study, donor-derived cell-free DNA (dd-cfDNA) discriminated biopsy-based diagnosis of active rejection in kidney transplant patients but serum creatinine (sCr) level did not. This analysis examines the performance of sCr increase from a baseline to discriminate active rejection at a clinically-indicated biopsy. A 15 to 25% increase over baseline is often used in studies to define unstable graft function that may be attributable to rejection or other causes. Methods: Increases of >15, >20 and >25% in sCr in the 60 days preceding clinically indicated or surveillance biopsies were identified among 392 patients in the DART study. Performance of dd-cfDNA at the time of clinical suspicion (prior values for dd-cfNA were not generally available) was compared to the performance of the change in sCr for discrimination of biopsy-based diagnosis of active antibody mediated and/or cellular rejection. Results: 117 patients had 136 visits that included a biopsy, dd-cfDNA measurement, and both concurrent and prior sCr measurements. Of 136 biopsies, 36 were for surveillance and 2 for follow-up of rejection treatment. Of 98 clinically-indicated biopsies, 24 were diagnosed as active rejections and 74 as no rejection. In these, the median dd-cfDNA in active rejection was 2.03%, whereas the median in no rejection was 0.33%. The median change in sCr was 10% in active rejection and 0% in the no rejection group. The C-statistic for change in sCr was marginally significant at 0.60 (95% CI 0.51-0.69), whereas the C-statistic for dd-cfDNA was 0.80 (0.71-0.88). At thresholds of 1% for dd-cfDNA and 25% change for sCr, the positive predictive values were 64% and 37% and the negative predictive values were 86% and 72% respectively. Conclusions: Increases in sCr from baseline are slightly better than sCr value alone, which is not effective at all, to identify which patients undergoing clinically-indicated biopsies are likely to render histologic findings of active rejection. dd-cfDNA provides more accurate identification of active rejection than the change in sCr or single sCr value. Future studies will provide data on the performance of dd-cfDNA increase to predict rejection prior to or regardless of changes in sCr.
CITATION INFORMATION: Weir M., Hiller D., Yee J., Matas A. Donor-Derived Cell-Free DNA Outperforms Serum Creatinine Changes for Identifying Kidney Transplant Rejection Am J Transplant. 2017;17 (suppl 3).
To cite this abstract in AMA style:
Weir M, Hiller D, Yee J, Matas A. Donor-Derived Cell-Free DNA Outperforms Serum Creatinine Changes for Identifying Kidney Transplant Rejection [abstract]. https://atcmeetingabstracts.com/abstract/donor-derived-cell-free-dna-outperforms-serum-creatinine-changes-for-identifying-kidney-transplant-rejection/. Accessed December 2, 2024.« Back to 2018 American Transplant Congress