Hidden Non-Adherence to Tacrolimus after Kidney Transplantation: Insights from Self-Report and Intra-Patient Variability

Despite routine therapeutic drug monitoring after kidney transplantation, medication non-adherence often remains unrecognized until clinically relevant consequences become evident. This study aimed to assess medication adherence in kidney transplant recipients using self-reported measures and tacrolimus intra-patient variability (IPV), and to examine their association with graft function. This hybrid study combined a cross-sectional assessment of medication adherence with a prospective cohort follow-up. Tacrolimus trough concentrations, IPV, and estimated glomerular filtration rate (eGFR) were monitored over four consecutive routine visits (6–8 months). For each patient, eGFR was modelled as a function of time using simple linear regression, and the regression coefficient was used as the individual eGFR slope. Medication adherence was assessed using the BAASIS questionnaire. Associations between self-reported adherence, tacrolimus IPV (%CV), and graft function were analysed using the Mann–Whitney U and Kruskal–Wallis tests. More than half of the participants (31 patients, 54.4%) reported non-adherence, predominantly related to dosing-time deviations rather than missed doses. These deviations were associated with increased tacrolimus intra-patient variability. Patients with higher tacrolimus variability had lower mean eGFR during follow-up, although no significant differences in longitudinal eGFR decline were observed. Increased tacrolimus IPV was associated with self-reported medication non-adherence, predominantly reflecting dosing-time deviations. Although these deviations did not result in a significantly faster decline in graft function during the 6–8-month follow-up, they increased tacrolimus variability, highlighting the importance of continued adherence monitoring to prevent greater variability and potential long-term adverse outcomes.