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Updated: May 16, 2025
Quantification of the Immunosuppressant Tacrolimus on Dried Blood Spots Using LC-MS/MS
Published on: November 8, 2015
Intrapatient tacrolimus variability is associated with medical nonadherence among pediatric kidney transplant
Tara B Gavcovich1,2, Vaka K Sigurjonsdottir1,2, Marissa J DeFreitas1,2
1Division of Pediatric Nephrology, Department of Pediatrics, University of Miami Miller School of Medicine, Miami, FL, United States.
Background:
Long-term survival of kidney allografts is limited by multiple factors, including nonadherence. High intrapatient variability in tacrolimus levels (≥30%) is associated with de novo donor-specific antibody (dnDSA) formation, increased risk of rejection and graft loss.
Methods:
We prospectively analyzed the association between tacrolimus intrapatient variability and nonadherence in pediatric kidney transplant recipients. We derived a composite adherence score from 0 to 3 points based on (1) Basel Assessment of Adherence to Immunosuppressive Medical Scale©; (2) healthcare team score; and (3) intentionally missed laboratory or clinic visits. A score of 1 or more was considered nonadherent. Tacrolimus 12 h trough levels, patient characteristics and clinical outcomes were collected. Tacrolimus IPV was calculated as the coefficient of variation.
Results:
The nonadherent group had a significantly higher median tacrolimus intrapatient variability (31%) as compared to the adherent cohort (20%) (p < 0.001.) Tac IPV demonstrated strong predictive performance for adherence (AUC 0.772), with a particularly high sensitivity of 90% at thresholds up to 20%, offering a practical and actionable framework for assessing adherence-related risks in clinical practice.
Conclusions:
Tacrolimus intrapatient variability may be a useful biomarker to identify nonadherence and high-risk patients, allowing for early interventions to prevent adverse graft outcomes.
Insights
High tacrolimus variability in kidney transplant patients may signal nonadherence. This finding helps identify at-risk individuals for early intervention, improving long-term graft survival.
Area of Science:
- Nephrology
- Transplantation immunology
- Pharmacokinetics
Background:
- Long-term kidney allograft survival is challenged by factors like nonadherence.
- High intrapatient variability (IPV) in tacrolimus levels (≥30%) correlates with de novo donor-specific antibody formation, rejection, and graft loss.
Purpose of the Study:
- To investigate the association between tacrolimus IPV and medication nonadherence in pediatric kidney transplant recipients.
- To establish tacrolimus IPV as a potential biomarker for identifying nonadherent patients.
Main Methods:
- Prospective analysis of pediatric kidney transplant recipients.
- Composite adherence score derived from the Basel Assessment of Adherence to Immunosuppressive Medical Scale, healthcare team assessment, and missed appointments.
- Tacrolimus 12-hour trough levels and intrapatient variability (IPV) calculated as coefficient of variation.
Main Results:
- Nonadherent patients exhibited significantly higher median tacrolimus IPV (31%) compared to adherent patients (20%) (p < 0.001).
- Tacrolimus IPV showed strong predictive performance for adherence (AUC 0.772), with 90% sensitivity at thresholds up to 20%.
Conclusions:
- Tacrolimus IPV can serve as a valuable biomarker for detecting nonadherence in kidney transplant recipients.
- Early identification of high-risk patients through tacrolimus IPV monitoring enables timely interventions to prevent adverse graft outcomes.
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