Dried Blood Spot for CXCL-10 and Tacrolimus: Integrated Non-Invasive Monitoring to Guide Personalized Treatment in...

Background/objectives: Kidney transplant recipients require lifelong immunosuppression and monitoring to prevent rejection, infection, and graft dysfunction. Current surveillance relies on tacrolimus therapeutic drug monitoring and, when needed, invasive biopsies. Dried blood spot (DBS) sampling provides a minimally invasive, patient-friendly option for remote follow-up. This study aims to develop and evaluate a DBS-based method for CXCL-10 quantification that, in combination with tacrolimus exposure monitoring, could help identify kidney recipients at risk of rejection and cytomegalovirus (CMV) infection and guide immunosuppression adjustment. Methods: The study included 81 selected kidney recipients for CXCL-10-DBS analysis by ELISA (12 T-cell mediated rejection; 10 antibody-mediated rejection; 6 CMV infection and 53 clinical event-free) and 10 healthy volunteers. A Tacrolimus-DBS LC-MS/MS method was developed and validated, and it was compared with the reference method on venous whole blood (WB) LC-MS/MS in a validation cohort (n = 160) and a clinical cohort (n = 36) using linear regression, Passing-Bablok and Bland-Altman analyses. Results: CXCL-10-DBS concentrations were significantly higher in rejectors (p < 0.001), with intermediate increases in CMV infection in comparison with event-free patients and healthy volunteers. ROC analysis demonstrated excellent diagnostic accuracy for rejection (AUC: 0.952; cutoff: 216.2 pg/mL; sensitivity: 100%; specificity: 79%; PPV: 88%; NPV: 100%). In contrast, tacrolimus trough concentrations did not differ significantly among the three clinical groups but showed strong correlation and agreement between DBS and venous WB with no systematic or proportional bias. Conclusions: This pilot study demonstrates the feasibility and diagnostic potential of DBS-based CXCL-10 measurement in adult kidney recipients. Integration of DBS-tacrolimus monitoring supports a minimally invasive pharmacokinetic-pharmacodynamic approach for personalized immunosuppression management.