#2586 Urinary and blood mRNA biomarkers for detecting kidney allograft rejection (The KTD-Innov study: NCT03582436)

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Abstract Background and Aims Blood and urinary mRNA biomarkers are non-invasive tools with potential for detecting kidney allograft rejection. However, their ability to provide added diagnostic value beyond current standard-of-care (SOC) patient monitoring remains unclear. Method In this prospective study, adult kidney transplant recipients were enrolled across seven French referral centres between July 2018 and December 2019 (ClinicalTrials.gov, NCT03582436). During the first-year post-transplantation, we quantified 19 blood and 12 urinary mRNA biomarkers during kidney allograft biopsies, including both protocol-specified and clinically indicated procedures. Primary outcome was the occurrence of allograft rejection, including antibody-mediated rejection (AMR), T cell-mediated rejection (TCMR), and mixed rejection, classified according to the Banff 2019 criteria. Results Overall, 733 kidney transplant patients (64.1% male, 35.9% female) were included, with 1,549 biopsies paired with the mRNA biomarkers. The cumulative incidence of rejection was 9.7% (95% CI; 7.6%–12.1%). None of the blood biomarkers tested (AKR1C3, CD3E, CD4, CD40, CD8A, CD9, CTLA4, ENTPD1, FOXP3, GZMB, ID3, IL7R, MS4A1, MZB1, POU2AF1, POU2F1, TCL1A, TLR4, and TRIB1) had a significant association with allograft rejection (Fig. 1A). However, among the 12 urinary biomarkers (CXCL9, CD25, CD3, Perf, NKG2∼4, FN1, PSMB10, PSMB9, αSMA, IP10, GZB, ECadh), eight-out-of-twelve, CXCL9 (p = 0.001), CD3 (p = 0.001), Perforin (p < 0.001), NKG2∼4 (p < 0.001), PSMB10 (p ≤ 0.001), PSMB9 (p = 0.005), aSMA (p = 0.043), IP10 (p = 0.006) were significantly associated with allograft rejection (Fig. 1B). Moreover, PSMB9 was the only urinary biomarker to show a discriminatory ability between TCMR and AMR (p = 0.022, higher in TCMR). Despite these findings, integrating urinary biomarkers with SOC monitoring parameters failed to improve predictive accuracy compared to SOC monitoring. Conclusion Urinary mRNA—but not blood—biomarkers showed significant associations with kidney allograft rejection during the first-year post-transplantation. Nonetheless, these biomarkers did not improve predictive performance when added to existing SOC practices, underscoring the need for further research to optimise non-invasive diagnostic strategies.