ASN's Mission

To create a world without kidney diseases, the ASN Alliance for Kidney Health elevates care by educating and informing, driving breakthroughs and innovation, and advocating for policies that create transformative changes in kidney medicine throughout the world.

learn more

Contact ASN

1401 H St, NW, Ste 900, Washington, DC 20005

email@asn-online.org

202-640-4660

The Latest on X

Kidney Week

Abstract: TH-PO1003

Next-Generation Transcriptomic Companion Tool for Molecular Assessment of Kidney Allograft Biopsies

Session Information

Category: Transplantation

  • 2001 Transplantation: Basic

Authors

  • Piedrafita, Alexis, Paris Institute for Transplantation and Organ Regeneration, Paris, France
  • Preka, Evgenia, Paris Institute for Transplantation and Organ Regeneration, Paris, France
  • Sablik, Marta, Paris Institute for Transplantation and Organ Regeneration, Paris, France
  • Thalamas, Thibaut, Paris Institute for Transplantation and Organ Regeneration, Paris, France
  • Larsen, Christopher Patrick, Arkana Laboratories, Little Rock, Arkansas, United States
  • Cassol, Clarissa Araujo, Arkana Laboratories, Little Rock, Arkansas, United States
  • Kamar, Nassim, Toulouse University Hospital, Toulouse, France
  • Lefaucheur, Carmen, Paris Institute for Transplantation and Organ Regeneration, Paris, France
  • Colvin, Robert B., Massachusetts General Hospital Research Institute, Boston, Massachusetts, United States
  • Mengel, Michael, University of Alberta Faculty of Medicine & Dentistry, Edmonton, Alberta, Canada
  • Loupy, Alexandre, Paris Institute for Transplantation and Organ Regeneration, Paris, France
Background

Histology remains central to kidney allograft biopsy interpretation, but incompletely captures the biological heterogeneity and continuum of injury, supporting the use of gene-expression profiling as a companion tool. Current molecular diagnostics remain largely restricted to rejection and do not integrate lesion-level activity or mechanistic phenotyping. We developed and validated a next-generation transcriptomic companion tool for interpretation of kidney allograft biopsies.

Methods

In 2314 kidney allograft biopsies from ten European and American centers, all Banff-graded and B-HOT profiled on nCounter, we developed and validated, an automated and user-friendly gene-expression based tool, processing independent samples to (i) predict pathological diagnoses, (ii) detect and assess severity of histological lesions (g, ptc, mvi, t, i, v, cg, ci, ct, cv, ifta), and (iii) document functional abnormalities including cell infiltration and pathways activation.

Results

Five diagnostic categories (Inflammation, Rejection, AMR, TCMR, BK virus nephropathy) were reliably predicted (AUROC»0.83-0.92 ; Brier Scores»0.08-0.12, FigureA). Histological lesions were accurately detected (AUROC 0.69-0.92 ; Brier scores 0.09-0.23, FigureB) and continuous molecular severity scores correlated well with lesion grade (Pearson’s r 0.35-0.80 ; C-Index 0.67-0.88, FigureC). Resulting probability space enabled separation of main diagnostic entities (Figure DE). Last, the tool provided biologically relevant insights cell infiltration (Pearson’s r > 0.6 with reference method) and pathways overactivation.

Conclusion

We developed a companion tool, easy to use, that reliably predicted diagnostics, histological lesions and functional endpoints, representing a step toward optimal exploitation of transcriptomic data to precision diagnostic in kidney transplantation.

Funding

  • Government Support – Non-U.S.