Intrapatient tacrolimus variability is associated with medical nonadherence among pediatric kidney transplant recipients

BackgroundLong-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.MethodsWe prospectively...

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Main Authors: Tara B. Gavcovich, Vaka K. Sigurjonsdottir, Marissa J. DeFreitas, Claudia Serrano, Esther Rivas, Migdalia Jorge, Wacharee Seeherunvong, Chryso Katsoufis, Wendy Glaberson, Melisa Oliva, Adela D. Mattiazzi, Carolyn Abitbol, Jayanthi Chandar
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-03-01
Series:Frontiers in Transplantation
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Online Access:https://www.frontiersin.org/articles/10.3389/frtra.2025.1572928/full
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Summary:BackgroundLong-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.MethodsWe 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.ResultsThe 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.ConclusionsTacrolimus intrapatient variability may be a useful biomarker to identify nonadherence and high-risk patients, allowing for early interventions to prevent adverse graft outcomes.
ISSN:2813-2440