Journal Article

CNI Trough Variability Does Not Reliably Reflect Medication Adherence: Insights From a 3-Year Follow-Up Study

Couzi, Lionel, Kamar, Nassim, Westeel, Pierre-Francois, Thierry, Antoine, Monchaud, Caroline, Villeneuve, Claire, Esposito, Laure, Rerolle, Jean-phillipe, Marquet, Pierre, Etienne, Isabelle, Büchler, Mathias

2026

Overview

Calcineurin inhibitor (CNI) trough concentrations and their variability are frequently used as adherence proxies, despite limited validation. We evaluated the association between self-reported adherence and CNI exposure during the first year after kidney transplantation. We included 619 patients from two prospective French cohorts (14,829 C 0 values). Adherence was assessed using the MMAS-4 questionnaire. CNI exposure was evaluated via C 0 levels, intra-patient variability (IPV; CV threshold = 30%), and underexposure rates. Cross-sectional and longitudinal analyses were performed. No significant differences in C 0 , IPV, or underexposure were observed between adherent and non-adherent patients, regardless of the CNI used or analytical approach. In longitudinal analysis, IPV was similar (31.3% [25.5–38.2] vs. 31.6% [23.6–38.9], p = 0.68), as was the proportion of patients with high IPV (55.5% vs. 51.5%, p = 0.5). At 3 years, high IPV was not significantly associated with rejection (HR 1.02 [0.67–1.55], p = 0.93). Self-reported adherence was not associated with CNI C 0 levels, IPV, or underexposure. CNI C 0 variability alone cannot reliably detect non-adherence and should not be interpreted as a standalone adherence marker. Multimodal strategies combining pharmacokinetics with validated self-report tools are needed to evaluate adherence.

• Publisher: Frontiers Media SA,Frontiers Media S.A
• Subject: adherence / Adult / calcineurin inhibitor (CNI) / Calcineurin inhibitors / Calcineurin Inhibitors - administration & dosage / Calcineurin Inhibitors - blood / Calcineurin Inhibitors - pharmacokinetics / Calcineurin Inhibitors - therapeutic use / Cross-Sectional Studies / Drug Monitoring / Female / Follow-Up Studies / France / Graft rejection / Graft Rejection - prevention & control / Humans / Immunosuppressive Agents - therapeutic use / Kidney Transplantation / Kidney transplants / Longitudinal Studies / Male / Medication Adherence / Middle Aged / Missing data / Original Research / Patient compliance / Pharmacokinetics / Prospective Studies / Questionnaires / Self Report / Surveys and Questionnaires / Tacrolimus / trough concentrations (C0) / variability