Inclusion of CD8 Monitoring Improves the Prognostic Capacities of the Kidney Transplant Failure Score

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Introduction Beside the classical monitoring of kidney graft function using serum creatinine or proteinuria levels, the assessment of other non-invasive biomarkers has been proposed to identify patients at-risk of kidney rejection. To reach a true clinical utility, the prognostic capacities of a biomarker have to be higher than other available metrics such as clinical-based scoring system. We have previously shown that an increase in TEMRA CD8 T cells is associated with a 2-fold higher risk of long-term graft dysfunction. In this study, we evaluate if the monitoring of CD8-related biomarkers could improve the prognostic capacities of a clinical-based scoring system (Kidney Transplant Failure Score; KTFS). Methods 286 kidney-transplant recipients have been prospectively enrolled and followed for more than 8 years. At the end of the follow-up time, 51 patients returned to dialysis. Targeted analysis of 22 CD8 T cell subsets have been performed on blood samples retrieved 12 months post-transplantation. Results The frequency of EM and TEMRA CD8 measured at one year post-transplantation is correlated with the risk to return in dialysis during the 8 years follow-up. Moreover, we show that the prognostic capacity of the KTFS can be improved by the inclusion of the CD8 markers as the AUC of the biomarker-updated KTFS is 0.75 as compared to 0.71 a single predictor. Finally, when clinical based KTFS was used as inclusion criteria, we demonstrate that the use of one-year frequency of TEMRA CD8 allows the discrimination of patients that will lose their graft from those that will maintain stable graft function. Conclusion The combination of CD8-related biomarkers with clinical-parameters based KTFS allows to better predict patients at-risk of kidney graft failure and to target those with a more specific immunologic risk. Such score, after further validation on large external cohorts, could be useful as decision tool in the clinical management of kidney transplant recipients. Labex IGO (ANR-11-LABX-0016-01). FP7 VISICORT (602470). ANR-11-JSV1-0008-01. ITMO Santé Publique (A13053NS). Fondation Centaure. IHU CESTI (ANR-10-IBHU-005).