A comprehensive review of the impact of tacrolimus intrapatient variability on clinical outcomes in kidney transplantation

Tacrolimus (Tac) is widely used to prevent rejection and graft loss in solid organ transplantation. A limiting characteristic of Tac is the high intra and interpatient variability associated with its use. Routine therapeutic drug monitoring (TDM) is necessary to facilitate Tac management and to avoi...

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Bibliographic Details
Published in:American journal of transplantation 2020-08, Vol.20 (8), p.1969-1983
Main Authors: Gonzales, Haley M., McGillicuddy, John W., Rohan, Vinayak, Chandler, Jessica L., Nadig, Satish N., Dubay, Derek A., Taber, David J.
Format: Article
Language:English
Subjects:
Clinical outcomes
Drug therapy
Graft rejection
Graft Rejection - drug therapy
Graft Rejection - etiology
Graft Rejection - prevention & control
Graft Survival
health services and outcomes research
Humans
Immune system
immunosuppressant ‐ calcineurin inhibitor: tacrolimus
Immunosuppressive Agents - therapeutic use
Kidney Transplantation
kidney transplantation/nephrology
Kidney transplants
Risk factors
Survival
Tacrolimus
Therapeutic applications
Therapeutic drug monitoring
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Summary:Tacrolimus (Tac) is widely used to prevent rejection and graft loss in solid organ transplantation. A limiting characteristic of Tac is the high intra and interpatient variability associated with its use. Routine therapeutic drug monitoring (TDM) is necessary to facilitate Tac management and to avoid undesirable clinical outcomes. However, whole blood trough concentrations commonly utilized in TDM are not strong predictors of the detrimental clinical outcomes of interest. Recently, researchers have focused on Tac intrapatient variability (Tac IPV) as a novel marker to better assess patient risk. Higher Tac IPV has been associated with a number of mechanisms leading to shortened graft survival. Medication nonadherence (MNA) is considered to be the primary determinant of high Tac IPV and perhaps the most modifiable risk factor. An understanding of the methodology behind Tac IPV is imperative to its recognition as an important prognostic measure and integration into clinical practice. Therapeutic interventions targeting MNA and reducing Tac IPV are crucial to improving long‐term graft survival. This is a comprehensive review of tacrolimus intrapatient variability, including current measurement and reporting methods, its impact on clinical outcomes, and the clinical implications of this novel metric in kidney transplantation.
ISSN:1600-6135
1600-6143
DOI:10.1111/ajt.16002