BACKGROUND

SubAR can currently only be detected using surveillance biopsies (SBx) and is associated with poor long-term graft outcomes. Response to treatment is difficult to assess. We developed a peripheral blood gene expression profile (GEP) that can detect subAR. The objective of this study is to determine the clinical utility of serial GEP assessments to monitor resolution of subAR.

METHODS

KTR enrolled into a multi-center 24-mo observational study underwent SBx – those with subAR were managed per local practice; they subsequently had intensive monitoring (IM) consisting of blood samples every 2 wks and repeat Bx at week 8. IM was limited to 1 subAR episode per KTR.

RESULTS

23 KTR with subAR underwent IM and repeat bx. Central histology reads between baseline and repeat bx were used to assess resolution: 11 (47.8%) (3 untreated) showed histologic resolution (Group 1: 'resolved'), and 12 (52.2%) (1 untreated) showed persistent or worsening rejection (Group 2: 'unresolved'). Group 2 included a lower proportion of Borderline (6/12) and higher proportion of > Borderline (3 1A, 2 AMR, and 1 Borderline plus AMR) compared to Group 1: 9/11 Borderline (2 1A rejections) at baseline. Consistent with differences in severity of rejection between the 2 groups, we noted differences in the GEP predicted probability scores at baseline (p=0.073). Significant differences were observed between the 2 groups in the probability scores at 4 (p=0.014) and 8 (p=0.015) weeks. When values were adjusted for differences in baseline probabilities, these comparisons remained significant. Changes in the GEP probability scores between baseline and 4 (p=0.045) and 8 weeks (p=0.023) also differed significantly between the two groups.

CONCLUSIONS

Based on repeat Bx, our study shows that 12/23 (52%) KTR demonstrated persistence or worsening of subAR, including 11/19 (58%) who underwent treatment, suggesting a need for improved monitoring. A novel molecular GEP biomarker recently developed for the detection of subAR demonstrates the potential to monitor resolution of subAR following treatment.

CITATION INFORMATION: Zhao L., Armstrong B., Friedewald J., Whisenant T., Kurian S., Heilman R., Poggio E., Marsh C., Baliga P., Bridges N., Odim J., Brown M., Ikle D., Charette J., Brietigam S., Sustento-Reodica N., Kandpal M., Salomon D., Abecassis M. Serial Monitoring of Resolution of Sub-Clinical Acute Rejection (subAR) in Kidney Transplant Recipients (KTR) Using a Gene Expression Profile (GEP) Am J Transplant. 2017;17 (suppl 3).

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