*Purpose: Transcriptomics (Tr) is an emerging adjunct to traditional histological diagnosis (HDx) for kidney allograft rejection (KAR). We describe our experience of using Tr and dd-cfDNA for diagnosing rejection and treatment decisions.

*Methods: We incorporated serial dd-cfDNA and addition of Tr for cause kidney biopsies in the workflow of our clinic. We report on the insight gleaned from the cases that changed our traditional approach to diagnose and treat rejection. Serial dd-cf DNA were obtained in the context of routine clinical care at months 1,2,3,4, 6, 9 and 12 months post-transplant in the 1^st year post-transplant and every 3 months thereafter. Patients with dd-cfDNA within 30 days of Kidney allograft biopsies that were performed on a “for-cause” basis to assess for biopsy proven acute rejection (BPAR) were included in the study. Some patients had multiple biopsies; each biopsy was treated as a separate event.

*Results: Of 24 events of biopsies, HDx diagnosed rejection in 16 events, Tr diagnosed rejection in 8 events. HDx agreed with Tr in 24(66%) of events. The discordant findings were noticed in 8 events (33%) out of 24, where Tr did not diagnose rejection versus HDx which did diagnose rejection. Fifty percent of these discordant events not diagnosed by Tr were found to have borderline cell-mediated rejection (CMR), others were Banff-1a. These patients were noted to have median allosure of 0.24. However, when combined with clinical factors, review of patients, treatment decision, Tr was in agreement with clinical decision, considered gold standard, in 83% of cases, while HDx only in 66% of cases. It was interesting to note that Tr did classify five events as antibody-mediated rejection (AMR) out of 15 events diagnosed as CMR based by HDx. These 5 events were noted to have a higher median of dd-cfDNA (0.69) when compared to all events (median 0.26). Results of Tr when combined with dd-cf DNA did change our management plan of pursuing treatments to dampen antibody response in addition to treating CMR. dd-cf DNA showed a positive correlation with Tr rejection score (p=0.006), Figure 1.

*Conclusions: We show that Tr acts as a vital tool in CMR in both ruling out rejection and diagnosing ongoing early AMR which can be missed by HDx. Tr acts as an adjunct in addition to histology to refine treatment decisions and management decisions. Tr, dd-cfDNA should be incorporated in management of CMR patients to identify and treat early AMR and potentially improve long term outcomes. There is a need for prospective studies for further validation.

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