Early Monitoring of Donor-Derived Cell-Free DNA in Kidney Allograft Recipients Followed-Up for Two Years: Experience of One Center

Abstract

(1) Background: donor-derived circulating free DNA (dd-cfDNA), an innovative biomarker with great potential for the early identification and prevention of graft damage. (2) Methods: Samples were collected prospectively and the study was performed retrospectively to analyze dd-cfDNA plasma levels in 30 kidney transplant patients during their post-transplant follow-up (15 days, 3, 6, and 9 months), to determine if the result could be of interest in the identification of possible adverse events, especially rejection. The aim was to verify whether the data on sensitivity, specificity, NPV, and PPV compare with reference values and creatinine values. (3) Results: We observed levels of dd cfDNA > 1% in six of nine patients with active rejection (ABMR or TCMR) and elevated values (>0.5%) in two other patients in this rejection group. Our results show low values of sensitivity = 50%, specificity = 61.11%, rejection NPV = 64.71%, and rejection PPV = 46.13% of the technique compared to reference values previously published. With respect to creatinine, only for TCRM, we observed better results for dd-cfDNA in these parameters than in creatinine. Also, our data suggest that dd-cfDNA could help to differentiate those patients with dnDSAs that are going to through rejection better than creatinine, specially at 15 d post transplant. In this study, this appears to have no positive predictive value for borderline rejection (BR) or TCMR IA. (4) Conclusions: plasma levels of dd-cfDNA could be considered an additional or alternative biomarker for graft rejection monitoring in early post-kidney transplant up to several months before its clinical presentation, especially for patients with suspected TCMR or ABMR.

Keywords

• donor-derived circulating free DNA (dd-cfDNA)
• kidney transplant
• graft rejection
• biomarker
• non-rejection (NR)
• antibody-mediated rejection (ABMR)