Holman, John

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. Background Persistent 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. Methods This 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. Results A 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. Conclusions Both 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. Clinical Trial registration number: NCT01531257.

AbstractBackgroundThe aim of this study was to correlate peripheral blood gene expression profile (GEP) results during the first post‐transplant year with outcomes after kidney transplantation.MethodsWe conducted a prospective, multicenter observational study of obtaining peripheral blood at five timepoints during the first post‐transplant year to perform a GEP assay. The cohort was stratified based on the pattern of the peripheral blood GEP results: Tx‐all GEP results normal, 1 Not‐TX had one GEP result abnormal and >1 Not‐TX two or more abnormal GEP results. We correlated the GEP results with outcomes after transplantation.ResultsWe enrolled 240 kidney transplant recipients. The cohort was stratified into the three groups: TX n = 117 (47%), 1 Not‐TX n = 59 (25%) and >1 Not‐TX n = 64 (27%). Compared to the TX group, the >1 Not‐TX group had lower eGFR (p < .001) and more chronic changes on 1‐year surveillance biopsy (p = .007). Death censored graft survival showed inferior graft survival in the >1 Not‐TX group (p < .001) but not in the 1 Not‐TX group. All graft losses in the >1 Not‐TX group occurred after 1‐year post‐transplant.ConclusionsWe conclude that a pattern of persistently Not‐TX GEP assay correlates with inferior graft survival.