Epigenetic signatures on plasma cell-free DNA to detect kidney allograft rejection in a non-invasive way: development of a 10-plex digital PCR assay
Abstract
The standard of care for the follow-up of kidney allograft recipients combines non-invasive but non-specific biomarkers and kidney biopsies for the gold standard histology-based diagnosis, limited by the sampling bias, haemorrhagic risk, and low cost-effectiveness. We hypothesized that a targeted epigenetic analysis of cell-free DNA (cfDNA) would combine non-invasiveness and specificity for the diagnosis of kidney allograft rejection. We developed an in silico pipeline to identify 9 specific methylation signatures of epithelial or endothelial cell types in glomerular and tubular kidney compartments. Methylation-specific digital Polymerase Chain Reaction (dPCR) were designed and validated for these markers and combined in a 10-plex dPCR. In a retrospective cohort of 170 plasma cfDNA from adult kidney transplant recipients, we evaluated the diagnostic properties of our biomarkers for predicting rejection, evaluated on solid biopsy according to Banff 2022 classification. Combining the dedicated biomarkers with standard-of-care blood tests (donor-specific antibody (DSA), estimated glomerular filtration rate (eGFR)) produced a prediction model with an Area under the Curve (AUC) for biopsy-proven kidney transplant rejection vs. no rejection greater than with DSA and eGFR alone (AUC = of 0.884 vs. 0.776, p = 0.0005). In an alternative model for the prediction of any graft lesion of Banff classification vs. pristine biopsies (all Banff score = 0) epigenetic kidney biomarkers…
How strong is the evidence?
Evidence Hub reads this as a cohort study, done in people. Its evidence level is 3 of 5 (Moderate · trial / cohort / secondary analysis). Trials without a large randomized design, cohorts and secondary analyses give moderate evidence.
Read the paper
Related studies
- Combining in silico and in vitro approaches to identification of potent inhibitor against phospholipase A2 (PLA2)
- In silico and in vitro studies: investigating the chemical composition, DFT, molecular docking, and dynamic simulation of Satureja candidissima (Munby) Briq essential oil as a potential antibacterial agent
- Quercetin combined with ciprofloxacin and gentamicin inhibits biofilm formation and virulence in Staphylococcus aureus
- In silico study of the mechanism of action, pharmacokinetic and toxicological properties of some N-methylanthranilates and their analogs
- Anticonvulsant Effects of Citronellal, Daidzin, and Phytol, Possibly Through GABAA Receptor and Voltage-Gated Sodium Channel Interaction Pathways: In Vivo and In Silico Studies
- 2-Phenylcyclopropylmethylamine (PCPMA) Derivatives as D3R-Selective Ligands for 3D-QSAR, Docking and Molecular Dynamics Simulation Studies
Go deeper in Evidence Hub
Evidence Hub adds a study data sheet (design, sample size, evidence level, key numbers), an AI summary and a chat grounded in the paper's text.