Clinical Value of Peripheral Blood Gene Expression Profile and Donor-Derived Cellfree DNA for Identifying Persistent Rejection

Abstract

Key Points Peripheral blood biomarkers may have value in monitoring kidney transplant recipients after treatment of acute rejection.The donor-derived cellfree DNA may be more sensitive to identifying antibody-mediated rejection and gene expression profile may be more sensitive to identifying acute cellular rejection.BackgroundPersistent rejection is an increasingly recognized barrier to long-term kidney allograft survival. A noninvasive method to help identify patients with persistent rejection in need of biopsy would be valuable.MethodsThis was a post hoc analysis of a multicenter observational study. Patients who had a biopsy-proven acute rejection, had another biopsy within 9 months (270 days), and had a biopsy-paired biomarker sample were included.ResultsA total of 64 index rejections in 58 patients with repeat biopsies were identified with a median time to repeat biopsy of 100 days. Persistent rejection was present in 61%; 69% of follow-up biopsies were performed in clinically stable patients. Peripheral blood gene expression profile (GEP) demonstrated a sensitivity of 59%, specificity of 76%, positive predictive value (PPV) of 79%, and negative predictive value of 54%. Donor-derived cellfree DNA (dd-cfDNA) demonstrated a sensitivity of 62%, specificity of 86%, PPV of 88%, and negative predictive value of 56%. For repeat biopsies within 90 days of rejection in clinically stable patients (63% of repeat biopsies), both GEP and dd-cfDNA had specificities and PPVs of 100%. GEP was more likely to be positive in T-cell-mediated rejection while dd-cfDNA was more likely to be positive in antibody-mediated rejection.ConclusionsBoth GEP and dd-cfDNA may have utility in identifying clinically stable patients with persistent rejection in need of biopsy; however, they identify different types of rejections.