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Kidney Week

Abstract: PO2039

Urinary Cell mRNA Profile Diagnosis of Borderline T Cell-Mediated Rejection in Kidney Allografts

Session Information

Category: Transplantation

  • 1902 Transplantation: Clinical

Authors

  • Salinas, Thalia, Weill Cornell Medicine, New York, New York, United States
  • Li, Carol Y., Weill Cornell Medicine, New York, New York, United States
  • Snopkowski, Catherine, Weill Cornell Medicine, New York, New York, United States
  • Chen, Kevin, Weill Cornell Medicine, New York, New York, United States
  • Albakry, Shady Y., Weill Cornell Medicine, New York, New York, United States
  • Salvatore, Steven, Weill Cornell Medicine, New York, New York, United States
  • Seshan, Surya V., Weill Cornell Medicine, New York, New York, United States
  • Lee, John Richard, Weill Cornell Medicine, New York, New York, United States
  • Muthukumar, Thangamani, Weill Cornell Medicine, New York, New York, United States
  • Dadhania, Darshana M., Weill Cornell Medicine, New York, New York, United States
  • Suthanthiran, Manikkam, Weill Cornell Medicine, New York, New York, United States
Background

Borderline rejection (BR) is associated with inferior outcomes. In CTOT-04, 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 is diagnostic of BR.

Methods

Urinary cell mRNAs measured in 377 biopsy-matched urine samples from 300 kidney transplant recipients. Interstitial inflammation (i) and tubulitis (t) scored by Banff criteria. Diagnosis of BR=i1,t1, i2,t1, or i1,t2 and TCMR= i≥2,t≥2 (Loupy et al.Am J Transplant,2020). Exclusion criteria: inadequate biopsy;BKVN;+BKVN by urinary BKV-VP1 mRNA level(Dadhania et al.Transplantation,2010),i1 or t1 alone. RNA isolated from urinary cell pellet, absolute transcript levels measured by customized RT-qPCR and CTOT-04 signature computed.

Results

293 biopsies included (Table 1). CTOT-04 signature distinguished i0,t0 biopsies from BR and TCMR(p<0.0001,ANOVA)(Fig.1A).18S normalized CD3ε and IP-10 mRNAs elevated in BR and TCMR urine(Fig.1D-E).Accurate diagnosis of BR and TCMR shown(Table 2A-B).

Conclusion

Urinary-cell CTOT-04 signature discriminates i0,t0 from BR or TCMR biopsies. Our findings may help reduce biopsies performed to diagnose BR or TCMR and prognosticate graft outcome.