Cell-Free DNA Levels and Prediction of Rejection Resolution in Kidney Transplant Recipients

Background: The diagnosis and confirmation of kidney transplant rejection currently relies on biopsy. Once rejection is detected and treated, practice varies in terms of whether patients undergo follow-up biopsies to confirm resolution of rejection. We hypothesized that cell-free DNA levels could predict graft outcomes following treatment for rejection. Methods: We recruited children or adults at time of their scheduled biopsy (either for surveillance or due to rise in serum creatinine). If rejection was detected, participants were then followed prospectively over time with cell-free DNA levels drawn quarterly for up to a 1-year period. Mixed logistic models were used to examine cell-free DNA levels over time as a predictor of subsequent rejection diagnosed by a repeat biopsy (if performed), clustered by patient. If no repeat biopsy was performed, patients were presumed to have had resolution of their rejection. Generalized estimating equations were used to examine change in eGFR levels by the CKD-EPI equation. All models were adjusted for age, sex, race, and donor type. Results: Among 154 participants, 52 (34%) had rejection at enrollment and were followed propsectively over time (Table). Of those with rejection, 56% had borderline changes, 23% had antibody-mediated rejection, 10% had cellular rejection, 12% had mixed rejection types. With every 1% percentage point increase in cell-free DNA levels during follow-up, the odds of persistent rejection was 1.32 times higher (95% CI 1.15-1.51) in unadjusted analysis and similar in adjusted analysis (OR 1.28; 95% CI 1.13-1.45). For every 1 percentage point increase in cell-free DNA level over the initial value, the eGFR was 0.18 mL/min/1.73 m2 lower (95% CI -1.9, 1.6; p=0.84) and not statistically significant. Results were similar in adjusted analysis (-0.56 mL/min/1.73 m2, 95% CI -2.2, 1.1). Conclusion: Change in cell-free DNA levels are predictive of persistent rejection during follow-up after a diagnosis of rejection. Funding: Commercial Support - Natera