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

Background: Long-term survival of kidney allografts is limited by multiple factors, including nonadherence. High intrapatient variability (IPV) in tacrolimus levels (≥30%) is associated with de novo donor-specific antibody ( dn DSA) formation, increased risk of rejection and graft loss. Methods: We prospectively analyzed the association between tacrolimus IPV 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 ^Ó ; (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 IPV (31%) as compared to the adherent cohort (20%) (p < 0.001), with a positive correlation between tacrolimus IPV and composite adherence score (r = 0.44, p < 0.001). Antibody and T-cell mediated rejection, along with dn DSA formation were more prevalent in nonadherent patients and those with a high tacrolimus IPV. Conclusions: Tacrolimus IPV may be a useful biomarker to identify high-risk patients, allowing for early interventions to prevent adverse graft outcomes.