Intrapatient Tacrolimus Variability is Associated with Medical Nonadherence among Pediatric Kidney Transplant Recipients

Tara Gavcovich ^1,2* Vaka Sigurjonsdottir ^1,2* Marissa DeFreitas ^1,2 Claudia Serrano ^1,2 Esther Rivas ^1,2 Migdalia Jorge ^1,2 Wacharee Seeherunvong ^1,2 Chryso Katsoufis ^1,2 Wendy Glaberson ^1,2 Melisa Oliva ³ Adela Mattiazzi ⁴ Carolyn L Abitbol ^1,2 Jayanthi J Chandar ^1,2

• ¹ Division of Pediatric Nephrology, Department of Pediatrics, Leonard M. Miller School of Medicine, University of Miami, Miami, Florida, United States
• ² Miami Transplant Institute, Jackson Health System, Miami, Florida, United States
• ³ Division of Pediatric Psychology, Department of Psychology, Jackson Health System, Miami, United States
• ⁴ Division of Nephrology, Department of Internal Medicine, University of Miami Miller School of Medicine and Jackson Memorial Hospital, Miami Transplant Institute, Miami, 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 0-3 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-hour 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.