38 - Determinants and outcomes of tacrolimus dose and exposure variability in pediatric renal transplant recipients

Sunday, April 30, 2023

3:30 PM – 6:00 PM ET

Poster Number: 38
Publication Number: 38.349

Yi Shi, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, United States; Asha Moudgil, Children's National Health System, Washington, DC, United States

Presenting Author(s)

Yi Shi, MD, PharmD

Assistant Professor of Pediatrics
Columbia University Vagelos College of Physicians and Surgeons
New York, New York, United States

Background: Tacrolimus is used for maintenance of immunosuppression in patients with solid organ transplantation. Absorption and metabolism vary dramatically among individuals based on several factors such as age, race, and drug metabolism. High intra-patient tacrolimus variability (TV) and dose required to achieve therapeutic trough concentration (C/D), a proxy for drug metabolism, may affect graft outcomes.

Objective:

To assess the association of demographic factors (age, race, gender, and insurance) with intra-patient TV and tacrolimus C/D in pediatric kidney transplant recipients. Additionally, the impact of TV and C/D ratio was assessed on adverse clinical outcomes (AR, DSA development, rapid decline in eGFR, and composite outcomes).

Design/Methods: Retrospective data was collected for first renal transplant recipients aged 1-20 years, at Children’s National Hospital between 1/1/2011- 9/30/2019. Only patients who received thymoglobulin induction and tacrolimus during the first-year post-transplant were included. Generalized linear mixed models and chi-square methods were used for analysis.

Results: 95 patients met inclusion criteria for the study. Intrasubject variability was highest among age quintiles of 6-15 years old (p = < 0.0001), non-white race (p = 0.000030), and those with public insurance (p= 0.0049). Lower C/D ratio showed a significant association with age (p = 3.62^-9), and with non-white race (p = 0.0488). Only in patients with ≥40% coefficient of variation of tacrolimus, there was an increased risk of de novo DSA formation (p = 0.001), decline in eGFR >10 ml/min/1.73m2 (p = 0.016), and the composite outcome (p = 0.035). Lower C/D ratio was associated with an eGFR decline >10 mL/min/1.73m2 (p = 0.05).

Conclusion(s): There is higher intra patient variability in tacrolimus levels based on age, non-white race, and public insurance, and was not associated with adverse outcomes in the first year of transplant unless the variability was ≥40%. Higher tacrolimus doses are required to achieve therapeutic concentrations in the younger age and non-white race groups and are associated with a greater decline in eGFR during the first year of transplant. Additional studies are needed to verify these associations.