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).

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