The Effect of Genetic Polymorphism on Tacrolimus Metabolization Rate Due to Racial Variability and Its Impact on Kidney Transplantation

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Date of Award

Spring 2025

Document Type

Dissertation

Degree Name

Doctor of Healthcare Administration (DHA)

Committee Chair

Bora Pajo

Committee Member

Gail Frankle

Committee Member

Lewis Chongwony

Abstract

This quantitative study examined tacrolimus intrapersonal variability (IPV) between racial groups and explored antibody-mediated rejection and graft loss predictors in kidney transplantation. The study included 521 adult kidney allograft recipients at Columbia University Irving Medical Center from January 1, 2015, to December 31, 2018. A one-way ANOVA revealed significant differences in IPV across racial groups (F(3, 517) = 7.745, p < 0.001). Post hoc multiple comparisons using Tukey’s HSD test indicated that African Americans (AAs) exhibited significantly higher IPV (M = 39.81%, SD = 15.71%) compared to Caucasians (M = 30.32%, SD = 15.57%), Hispanics (M = 29.66%, SD = 16.79%), and Others (M = 32.06%, SD = 14.43%). Cox regression analysis revealed that IPV negatively impacted kidney allograft survival (HR = 1.029, 95% CI [1.006 - 1.052], p = 0.014). Donor-specific antibodies (DSA) increased graft failure risk by four times (HR = 4.443, 95% CI [1.728 – 11.428], p < 0.002). Univariate analysis showed that high IPV (=>30%) significantly reduced graft survival (¿²(1) = 4.830, p = 0.028). Additionally, regraft (HR = 3.444, 95% CI [1.631 – 7.272], p = 0.001) and DSA (HR = 8.492, 95% CI [3.978 – 18.128], p < 0.001) were significant predictors of antibody-mediated rejection. In conclusion, racial variability in tacrolimus IPV significantly correlates with transplant outcomes, suggesting that genotyping-guided tacrolimus dosing may optimize drug levels and minimize rejection risk.

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