Tacrolimus Trough Level Variation and Its Correlation to Clinical Outcomes and Consequences in Solid Organ Transplantation

Abstract

Purpose

Tacrolimus is a calcineurin inhibitor that suppresses immunity by inhibiting T-lymphocyte activation. It has a high intra- and inter-patient variability in its pharmacokinetics. Therefore, therapeutic drug monitoring is required to individualize the dose. High tacrolimus trough level variability is associated with a higher risk of adverse effects. In practice, the initial dosing and sampling time of tacrolimus levels is not standardized, which may result in resource wastage, frequent blood sampling, and a longer time to achieve therapeutic levels. The aim of this study was to evaluate tacrolimus trough level variation and its correlation to clinical outcomes and consequences.

Patients and Methods

A retrospective cohort study At King Abdulaziz Medical City in Riyadh, Saudi Arabia, 01/01/2018 to 31/12/2021. Inclusion Criteria: >18 years old solid organ transplant patients who received tacrolimus as part of their initial immunosuppression regimen. Tacrolimus initial dosing, trough levels, and dose adjustments were recorded during the early post-transplantation period (first 10 days). The coefficients of variation (CV%) in tacrolimus doses and trough concentrations were calculated and compared for different demographics and clinical characteristics.

Results

The higher coefficient of variation in dose and trough level is associated with different demographic and clinical factors that will predict the incidence of adverse events. In our study, there was a significant increase in adverse effect reporting in the high variability group but was not clear for the risk of graft function, acute rejection, or infections.

Conclusion

The variation in trough levels is associated with clinical consequences. Therefore, better dosing strategies can be modified to reduce the variation (fluctuation) which is associated with poor outcomes.

Keywords:

• concentration
• variability
• monitoring
• clinical
• therapeutic

Acknowledgment

The authors would like to acknowledge the contributions of KAIMRC for helping in reviewing and approving the proposal and granting the IRB approval and ultimately for the preliminary research data.

Author Contributions

All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.

Disclosure

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Additional information

Funding

There is no funding information to disclose.