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Observational Study
. 2025 Jun 1;109(6):1026-1037.
doi: 10.1097/TP.0000000000005257. Epub 2024 Nov 18.

Blood Gene Expression Profiling and Donor-derived Cell-free DNA to Noninvasively Diagnose Clinical and Subclinical Kidney Transplant Rejection: A Real-life Appraisal Study

Joana Sellarés  1   2 , Franc Casanova  1   2 , M J Perez-Saez  3 , David Cucchiari  4 , Ana Coloma  5 , Anna Vila  6 , Carme Facundo  7 , Delphine Kervella  1   2 , Maria Molina  6 , Francesc Moreso  1   2 , Edoardo Melilli  5 , Fritz Diekmann  4 , Marta Crespo  3 , Oriol Bestard  1   2
Affiliations
Observational Study

Blood Gene Expression Profiling and Donor-derived Cell-free DNA to Noninvasively Diagnose Clinical and Subclinical Kidney Transplant Rejection: A Real-life Appraisal Study

Joana Sellarés et al. Transplantation. .

Abstract

Background: Peripheral blood biomarkers aim to noninvasively diagnose kidney allograft rejection, but most lack robust independent validation. TruGraf is intended to exclude subclinical cellular rejection (TCMR), whereas donor-derived cell-free DNA Viracor-TRAC has proven value in excluding antibody-mediated rejection (AMR). We aim to validate both biomarkers for accurate rejection diagnosis in a real-world clinical setting.

Methods: We prospectively included 230 unselected, consecutive kidney transplants from 6 centers undergoing for-cause and protocol biopsies with paired blood samples from December 2021 to 2022. TruGraf and Viracor-TRAC were blindly run by a central laboratory.

Results: The incidence of rejection was 22.6% (17.3% surveillance; 27% for-cause biopsies). Inflammation was associated with higher TRAC levels, with AMR/mixed and microvascular inflammation (MVI) showing the highest levels ( P < 0.05). TruGraf did not associate with any specific allograft injury. No biomarkers, individually or combined, accurately diagnosed any rejection (area under the receiver operating characteristic curve [AUROC] < 0.65). However, high TRAC levels, when combined with DSA in for-cause biopsies, predicted AMR/mixed rejection or MVI (AUROC = 0.817; P < 0.001), outperforming serum creatinine and DSA (AUROC < 0.65).

Conclusions: In this large, prospective, observational real-life study, we were unable to validate TruGraf and TRAC to diagnose rejection but found a useful context of use for TRAC to noninvasively diagnose AMR/mixed or MVI in conjunction with DSA in dysfunctioning graft.

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References

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