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Abstract: SA-PO1074

A Systematic Investigation on the Impact of Invasive Kidney Allograft Biopsy on Urinary Cell mRNA Profiles

Session Information

Category: Transplantation

  • 2102 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
  • Wright, Sheavonnie, Weill Cornell Medicine, New York, New York, United States
  • Lamba, Perola, Weill Cornell Medicine, New York, New York, United States
  • Suthanthiran, Manikkam, Weill Cornell Medicine, New York, New York, United States
Background

Liquid biopsies offer an unprecedented window into intragraft events. It is preferred that biospecimens are collected prior to biopsy since mechanical injury from this invasive procedure may alter circulating levels of biomarkers of interest, (Kyeso Y et al. Transplantation Direct 2021). In the Clinical Trials in Organ Transplantation (CTOT)-04 study consisting of 485 kidney transplant recipients (KTR), 298 biopsy-matched urine specimens were used to develop and validate a urinary cell 3-gene signature consisting of 18S rRNA normalized CD3ε mRNA and CXCL10 mRNA (CTOT-04 signature) and all but 10 specimens were collected at the time of biopsy or ≤3 days prior (Suthanthiran M et al. N Engl J Med 2013). There were no paired pre and post biopsy specimens to investigate the impact of kidney allograft biopsy on absolute copy numbers of the transcripts or CTOT-04 signature. The current study was designed to fill this gap in knowledge.

Methods

We collected urine from KTR before and after kidney allograft biopsy, both ≤6 hours of biopsy. We used the Weill Cornell Hybrid Protocol consisting of urine filtration to collect eluate with stable RNA and mRNA enrichment during RNA isolation using a silica-membrane-based cartridge (Salinas T et al. J Immunol Methods 2022). We measured absolute copy numbers of CD3ε mRNA, CXCL10 mRNA, and 18S rRNA (CTOT-04 signature), and mRNAs for TGFβ1, FOXP3, and BKV VP1 in urine samples collected pre and post kidney allograft biopsy.

Results

Box and whisker plots show that the various urinary cell mRNA levels and CTOT-04 signature score are not different between urine samples collected before and urine samples collected after kidney allograft biopsy (Fig. 1 A-G, All P values >0.05, Wilcoxon matched pairs signed-rank test).

Conclusion

Urinary cell mRNA levels and CTOT-04 signature score are not impacted by the kidney allograft biopsy and yield indistinguishable results irrespective of whether the urine was collected prior to or after the invasive kidney allograft biopsy procedure.

Funding

  • Other NIH Support