Trifecta-Kidney Study

Calibrating circulating donor-derived cell-free DNA against molecular biopsy assessments.

Investigators

Philip F Halloran, Jeff Reeve, Soroush Shojai, Sita Gourishankar and the MMDx-Kidney Study Group ()

Current screening methods for detecting rejection in kidney transplant patients, such as histology, creatinine levels, and urine protein analysis, have their limitations. To address this, the ß÷ßäÉçÇø Transplant Applied Genomics Centre has developed the Molecular Microscope® Diagnostic System (MMDx)—a groundbreaking molecular assessment tool for evaluating rejection and injury in kidney biopsies based on gene expression.

We are excited to introduce a new screening test: the Natera, Inc. dd-cfDNA Prospera™ test, which focuses on monitoring donor-derived cell-free DNA (dd-cfDNA) in blood. Our study aims to calibrate dd-cfDNA levels detected at the time of indication biopsies against MMDx measurements for different types of rejection, including T-cell mediated rejection (TCMR) and antibody-mediated rejection (ABMR) at various stages, as well as acute kidney injury (AKI) and late injury characterized by atrophy and fibrosis. We also want to determine if Prospera™ blood test can replace kidney biopsy test.

This research involves a comprehensive comparison of blood dd-cfDNA measurements with MMDx results, while also assessing HLA antibodies in the blood. The study is an extension of the INTERCOMEX project (ClinicalTrials.gov ID: ) and is currently being conducted across 27 centers in the US, Canada, Australia, and Europe.

Trifecta-Kidney Study Publications

  1. Halloran PF, Reeve J, Madill-Thomsen KS, Demko Z, Prewett A, Billings P, et al. The Trifecta Study: Comparing Plasma Levels of Donor-derived Cell-Free DNA with the Molecular Phenotype of Kidney Transplant Biopsies. J Am Soc Nephrol. 2022;33(2):387-400.
  2. Halloran PF, Reeve J, Madill-Thomsen KS, Demko Z, Prewett A, Gauthier P, et al. Antibody-mediated rejection without detectable donor-specific antibody releases donor-derived cell-free DNA: results from the Trifecta study. Transplantation. 2023;107(3):709-719..
  3. Halloran PF, Reeve J, Madill-Thomsen KS, Kaur N, Ahmed E, Cantos C, et al. Combining Donor-derived Cell-free DNA Fraction and Quantity to Detect Kidney Transplant Rejection Using Molecular Diagnoses and Histology as Confirmation. Transplantation. 2022;106(12):2435-42.

  4. Gauthier PT, Madill-Thomsen KS, Demko Z, et al. Distinct Molecular Processes Mediate Donor-derived Cell-free DNA Release From Kidney Transplants in Different Disease States. Transplantation. 2023;2023 Dec 27. doi: 10.1097/TP.0000000000004877. Online ahead of print.