Kidney Week

Abstract: PUB493

Validation of Donor-Derived Cell-Free DNA as a Biomarker for Antibody-Mediated Rejection in Kidney Transplant Recipients Late Post Transplantation

Session Information

• Publication Only

Category: Transplantation

• 2102 Transplantation: Clinical

Authors

• Lee, Grace Kai Hoon, Department of Medicine National University Hospital, Singapore, Singapore

Grace Kai Hoon Lee, DrMed

• Vathsala, Anantharaman, National University Centre for Organ Transplantation, National University Hospital, Singapore, Singapore

Anantharaman Vathsala, MD

• Sran, Hersharan, National University Centre for Organ Transplantation, National University Hospital, Singapore, Singapore

Hersharan Sran, MBBS

• D'Costa, Matthew, National University Centre for Organ Transplantation, National University Hospital, Singapore, Singapore

Matthew D'Costa, MD

• Chang, Zi Yun, National University Centre for Organ Transplantation, National University Hospital, Singapore, Singapore

Zi Yun Chang, MD, MBBS

• Wong, Emmett Tsz Yeung, National University Centre for Organ Transplantation, National University Hospital, Singapore, Singapore

Emmett Tsz Yeung Wong, MBBS, FASN

Background

Antibody-mediated rejection (ABMR) is a leading cause of late allograft failure in kidney transplant recipients (KTRs). Plasma donor-derived cell-free DNA (dd-cfDNA) is a non-invasive diagnostic biomarker for ABMR early post-transplant. As most studies evaluated KTRs at <3 years post-transplant, it is unclear if dd-cfDNA is useful in distinguishing ABMR from other findings in allografts >3 years post-transplant when superimposed on chronic inflammation and fibrosis. We hypothesise that dd-cfDNA is sensitive and specific for diagnosing late ABMR.

Methods

We conducted a single-centre, prospective, observational, pilot study. We recruited 27 KTRs with allograft dysfunction at >3 years post-transplant in whom a biopsy was planned. Plasma dd-cfDNA (AlloSeq®, CareDx, Brisbane, CA) was sent at the time of biopsy. Diagnostic characteristics were performed for dd-cfDNA and DSA, and dd-cfDNA correlated with Banff lesion scores.

Results

The median age of KTRs was 53 years (IQR 40, 55); 14 (52%) were living donor KTRs. Eighteen (67%) were Chinese and 7 (26%) were Malays. The median time post-transplant was 7.8 years (4.9, 11.7). Four (15%) KTRs had ABMR. Median dd-cfDNA was higher in KTRs with ABMR (1.95% vs 0.24%, p=0.004). Using a cut off of 1%, the AUROC for dd-cfDNA was 0.97. Its sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) to diagnose ABMR were 100%, 96%, 80%, 100%, vs. 100%, 91%, 67%, 100% for DSA. Combining dd-cfDNA with DSA achieved 100% sensitivity, specificity, PPV and NPV. Dd-cfDNA correlated positively with peritubular capillaritis (ptc, p=0.002) but not glomerulitis (g, p=0.070) scores when evaluated as continuous variables. Other than interstitial fibrosis (ci) scores (negative correlation, p=0.038), there was no significant correlation between dd-cfDNA and Banff chronicity scores.

Conclusion

In this pilot study, dd-cfDNA showed good diagnostic characteristics for ABMR late post-transplant and correlated positively with ptc scores. A lack of correlation between dd-cfDNA and chronicity scores suggests its utility as a predictor of late ABMR. This provides preliminary data for larger studies.