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

## TL;DR

A three-year study found that CNI trough variability does not reliably indicate medication adherence in kidney transplant patients.

## Contribution

This study demonstrates that CNI trough variability cannot be used alone to detect non-adherence in transplant patients.

## Key findings

- No significant differences in CNI trough levels or variability were found between adherent and non-adherent patients.
- High intra-patient variability was not associated with increased rejection risk at three years.
- Self-reported adherence did not correlate with CNI exposure metrics.

## Abstract

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 C0 values). Adherence was assessed using the MMAS-4 questionnaire. CNI exposure was evaluated via C0 levels, intra-patient variability (IPV; CV threshold = 30%), and underexposure rates. Cross-sectional and longitudinal analyses were performed. No significant differences in C0, 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 C0 levels, IPV, or underexposure. CNI C0 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.

Infographic summarizing a three-year study on CNI trough variability and medication adherence in renal transplant patients, showing no significant difference in intra-patient variability or rejection-free survival between adherence groups, with the conclusion that IPV is not a standalone indicator of adherence.