Urinary Cell CTOT-04 Signature is Diagnostic of Glomerulitis in Kidney Allograft Biopsies

T. Salinas¹, C. Li¹, C. Snopkowski¹, K. Chen¹, S. Albakry¹, S. Salvatore², S. Seshan², J. R. Lee¹, M. Thangamani¹, D. Dadhania¹, M. Suthanthiran¹

¹Nephrology, Weill Cornell-NYPH, New York, NY, ²Pathology, Weill Cornell-NYPH, New York, NY

Meeting: 2022 American Transplant Congress

Abstract number: 566

Keywords: Biopsy, Kidney transplantation, Non-invasive diagnosis, Rejection

Topic: Basic Science » Basic Clinical Science » 17 - Biomarkers: Clinical Outcomes

Session Information

Session Name: Biomarkers: Clinical Outcomes II

Session Type: Rapid Fire Oral Abstract

Date: Tuesday, June 7, 2022

Session Time: 5:30pm-7:00pm

Presentation Time: 6:10pm-6:20pm

Location: Hynes Ballroom A

*Purpose: Antibody mediated rejection is a significant complication after kidney transplantation and is an important cause of allograft failure. In the multicenter CTOT-04 study, we discovered and validated a urinary-cell signature of CD3ε mRNA, IP-10 mRNA and 18s rRNA diagnostic of TCMR (Suthanthiran et al. N Engl J Med,2013). We investigated whether this signature could detect glomerulitis, a form of microvascular inflammation that is a major feature of antibody mediated rejection.

*Methods: Urinary cell CTOT-04 score was measured in 382 biopsy-matched urine samples from kidney allograft recipients. Glomerulitis (g) was scored using Banff scores and scored as g0, g1, g2, or g3. Among the 382 biopsies, 58 were excluded from downstream analysis because of: inadequate biopsy (n=11); quality control failed for urinary cell mRNA/RNA too low (n=11), BKVN (n=16); urinary BKV-VP1 mRNA level diagnostic of BKVN (n=15); pyelonephritis (n=3), thrombotic microangiopathy (n=2). RNA was isolated from urinary cell pellets, absolute transcript levels were measured by customized RT-qPCR, and the CTOT-04 signature score was computed.

*Results: 324 biopsies from 260 kidney allograft recipients were included in analyses (Table 1). CTOT-04 signature score distinguished biopsies without glomerulitis from those with glomerulitis (ANOVA P=0.0002). Pair-wise comparisons showed that the score discriminated g0 biopsies from g1 biopsies (Mann-Whitney P=0.008), g0 from g2 (P=0.004), and g0 from g3 (P=0.0002). The CTOT-04 scores, based on Banff g scores are shown in Table 1 and illustrated in Figure 1.

*Conclusions: We have discovered and validated that urinary cell CTOT-04 signature is diagnostic of T cell-mediated rejection with a high degree of accuracy. Herein, we demonstrate that the urinary cell CTOT-04 signature discriminates kidney allograft biopsies with glomerulitis from those without glomerulitis. Altogether, our new findings suggest that AMR, associated with even minimal glomerular inflammation, can be diagnosed with a high degree of accuracy using the CTOT-04 signature originally developed for TCMR.

To cite this abstract in AMA style:

Salinas T, Li C, Snopkowski C, Chen K, Albakry S, Salvatore S, Seshan S, Lee JR, Thangamani M, Dadhania D, Suthanthiran M. Urinary Cell CTOT-04 Signature is Diagnostic of Glomerulitis in Kidney Allograft Biopsies [abstract]. Am J Transplant. 2022; 22 (suppl 3). https://atcmeetingabstracts.com/abstract/urinary-cell-ctot-04-signature-is-diagnostic-of-glomerulitis-in-kidney-allograft-biopsies/. Accessed May 30, 2025.

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