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A Multimodal Interrogation of Human Renal Allografts

D. Dadhania1, R. Ding1, H. Xu2, C. Lee1, C. Snopkowski1, T. Salinas1, T. Muthukumar1, J. Lee1, R. Woodward2, M. Grskovic2, S. Dholakia2, M. Suthanthiran1

1Weill Cornell Medicine - NYPH, New York, NY, 2CareDx, New York, NY

Meeting: 2021 American Transplant Congress

Abstract number: 394

Keywords: Gene expression, Kidney transplantation, Non-invasive diagnosis, Rejection

Topic: Clinical Science » Biomarkers, Immune Assessment and Clinical Outcomes

Session Information

Session Name: Biomarkers, Immune Assessment and Clinical Outcomes

Session Type: Poster Video Chat

Date: Saturday, June 5, 2021

Session Time: 7:30pm-8:30pm

 Presentation Time: 7:40pm-7:50pm

Location: Virtual

*Purpose: Development and validation of noninvasive biomarkers of kidney allograft rejection should improve transplant outcomes. CTOT-04 study validated urinary cell mRNA signature (CTOT04-Sig) for T-cell rejection (ACR). Plasma donor derived cell-free DNA (dd-cfDNA) levels were associated with antibody mediated rejection (ABMR) in a multicenter setting. We tested the hypothesis that a composite signature of CTOT04-Sig and plasma dd-cfDNA percentage is diagnostic of AR with high accuracy.

*Methods: We profiled biopsy matched 58 urine & plasma specimens from 55 graft recipients: 11 ACR, 10 AMR/mixed rejection, 22 ATI & 15 normal (Nl) biopsies. RNA from urine cell pellets was reverse transcribed to cDNA and customized PCR assays were used to measure CTOT04-Sig consisting of 18S rRNA normalized CD3E mRNA and IP-10 mRNA and 18S rRNA copies. AlloSure measurements were performed by CareDx using a targeted next-generation sequencing assay consisting of 405 single-nucleotide polymorphisms.

*Results:

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Table 1 is a summary of the study group characteristics.

Violin plots (Fig1A) show that the CTOT04-Sig score is significantly different increased in both ACR and AMR compared to ATI or Nl. dd-cfDNA is significantly increased in AMR vs. ACR, ATI or Nl (Fig1B).

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The ability of the signatures to distinguish AR (TCMR + AMR + Mixed) from No AR (ATI+ Normal) was analyzed using receiver operating characteristic (ROC) curves (Fig2). The composite signature had the highest area under the ROC (Fig2C) with a diagnostic accuracy of 90%, outperforming the CTOT04-Sig (P=0.045) and dd-cfDNA (P=0.028).

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*Conclusions: Composite signature of CTOT-04 signature and dd-cfDNA allows for accurate and specific diagnosis of AR of kidney allografts and this multimodal approach should be validated in a prospective, multicenter study.

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To cite this abstract in AMA style:

Dadhania D, Ding R, Xu H, Lee C, Snopkowski C, Salinas T, Muthukumar T, Lee J, Woodward R, Grskovic M, Dholakia S, Suthanthiran M. A Multimodal Interrogation of Human Renal Allografts [abstract]. Am J Transplant. 2021; 21 (suppl 3). https://atcmeetingabstracts.com/abstract/a-multimodal-interrogation-of-human-renal-allografts/. Accessed May 30, 2025.

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