*Purpose: Kidney Tissue Transcriptomics (Tr) is an emerging adjunct to traditional histology for diagnosis of kidney rejection in KTx. The objective assessment and reliance on Tr offers a vital, reliable tool for diagnosing early antibody mediated rejection (AMR) and confirming or refuting a borderline T- cell mediated rejection (TCMR) where subjectivity might alter decision making. We devised a clinical phenotype (CP) score and tested its correlation with Tr. We hypothesized 1) Tr results would match clinical phenotyping (CP) and be closer to the “ground truth” (GT) than traditional histological diagnosis (HDx); 2) treatment decision based on Tr would generate personalized targeted immunosuppression and potential cost-savings.

*Methods: Patients who underwent kidney biopsy for cause from July 2016 to Nov 2020 were included in the study. We incorporated Tr in the routine workflow for cause biopsies for KTx. CP scores utilized a scoring system for development of rejection clinical phenotype (Table 1). CP scores were assigned on retrospective chart review, with the observer blinded to pathology results. GT was the diagnosis that the clinician used to treat the patient which was considered gold standard. Treatment (TT) was treatment given to the patient. These were retrieved from retrospective chart review.

*Results: Of the 69 patients, the median score for CP was 1 (IQR 1-3). CP scores showed a significant, linear and positive correlation with Tr rejection scores (Fig 1). Tr and HDx both showed discordance with comparative standards- GT and TT(Fig 2). Overall, discordance of HDx was higher than Tr for both comparative standards-GT and TT. HDx disproportionately misdiagnosed more borderline acute cellular rejection (ACR) where no rejection (NR) based on GT and TT. Tr successfully diagnosed more acute antibody mediated rejection (AMR ) consistent with GT and TT, while HDx missed AMR when compared to the standard GT and TT.

*Conclusions:

Incorporating Tr pathophysiological based transcripts led to personalization and optimization of immunosuppression (IS) dose and type. Tr resulted in avoidance of overtreatment for ACR, while led to early therapeutic interventions for AMR to dampen early antibody response. Both treatment decisions have potential for cost savings and better patient outcomes, and improved allograft survival. CP scores at bedside are correlated with Tr scores, which can help triage, personalize IS dose and type while awaiting Tr results. Further studies need to validate the utility of CP score.

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