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Abstract: PO2395

Correlation of Donor-Derived Cell-Free DNA with Histology and Molecular Diagnoses of Kidney Transplant Biopsies

Session Information

Category: Transplantation

  • 1902 Transplantation: Clinical

Authors

  • Moinuddin, Irfan Ahmed, Virginia Commonwealth University, Richmond, Virginia, United States
  • Kamal, Layla, Virginia Commonwealth University, Richmond, Virginia, United States
  • Kumar, Dhiren, Virginia Commonwealth University, Richmond, Virginia, United States
  • King, Anne L., Virginia Commonwealth University, Richmond, Virginia, United States
  • Winstead, Ryan, Virginia Commonwealth University, Richmond, Virginia, United States
  • Halloran, Philip F., University of Alberta, Edmonton, Alberta, Canada
  • Gupta, Gaurav, Virginia Commonwealth University, Richmond, Virginia, United States
Background

Circulating donor-derived cell free DNA (ddcfDNA;CareDx,Brisbane,USA), a non-invasive test that could detect rejection in kidney transplants, was validated using histologic diagnoses. The interpretation of these findings could be difficult due to variable inter- and intra-observer agreement with regards to histologic diagnoses and evolving classifications overtime. The centralized Molecular Microscope(MMDx; Edmonton,CA) tissue gene expression platform may provide increased precision to traditional histology

Methods

In this single-center prospective study of 208 biopsies, we present novel data on calibration of cfDNA using simultaneous assessments of all ‘for-cause’ and surveillance biopsies with histology(Hx) and MMDx. AUC curves were calculated using the previously published ddcfDNA cut-offs of < 0.21% to rule-out rejection and >1% to rule-in rejection

Results

Of 208 biopsies done at a median of 5.8 months post-transplant, 108(52%) were done for allograft dysfunction; 74(36%) for surveillance (due to DSA) and 26(12%) for post-rejection treatment surveillance. There were significant discrepancies between Hx and MMDx; with MMDx(92; 44%) identifying a higher number of rejection cases vs Hx(79; 38%). While MMDx identified a higher number of antibody-mediated rejection cases(65; 31%) than Hx(43; 21%); the opposite was true for T-cell mediated rejection[TCMR; Hx:27(13%) vs MMDx: 13 (6%)]. AUC Curves for cfDNA concentration and prediction of rejection were more robustly correlated with MMDx(AUC=0.830; p<0.001) than with Hx(AUC=0.75; p<0.001). The median cfDNA levels decreased significantly in responders to rejection treatment(median 0.94 to 0.20; p=0.015) vs non-responders(0.76 to 0.82; p=0.25)

Conclusion

In this single-center study, for the first time we describe the calibration of ddcfDNA with simultaneous assessment of kidney transplant biopsy with traditional histology and MMDx. We confirmed and expanded on the data from the DART study where a cut-off≥1% was highly sensitive and specific for ruling-in rejection. We report the correlation of cfDNA with response to rejection therapy. We propose that the combination of tissue gene expression using the molecular microscope and blood-based ddcfDNA may add precision to traditional histology and could change future practice and treatment paradigms