Tacrolimus Trough Concentration Variability and Disparities in African American Kidney Transplantation

Background Low tacrolimus concentrations have been associated with higher risk of acute rejection, particularly within African American (AA) kidney transplant recipients; little is known about intrapatient tacrolimus variabilities impact on racial disparities. Methods Ten year, single-center, longitudinal cohort study of kidney recipients. Intrapatient tacrolimus variability was assessed using the coefficient of variation (CV) measured between 1 month posttransplant and the clinical event, with a comparable period assessed in those without events. Pediatrics, nontacrolimus/mycophenolate regimens, and nonrenal transplants were excluded. Multivariable Cox regression models were used to analyze data. Results One thousand four hundred eleven recipients were included (54.4% AA) with 39 521 concentrations used to assess intrapatient tacrolimus CV. Overall, intrapatient tacrolimus CV was higher in AAs versus non-AAs (39.9 19.8 % vs 34.8 +/- 15.8% P < 0.001). Tacrolimus variability was a significant risk factor for deleterious clinical outcomes. A 10% increase in tacrolimus CV augmented the risk of acute rejection by 20% (adjusted hazard ratio, 1.20, 1.13-1.28; P < 0.001) and the risk of graft loss by 30% (adjusted hazard ratio, 1.30, 1.23-1.37; P < 0.001), with significant effect modification by race for acute rejection, but not graft loss. High tacrolimus variability (CV >40%) was a significant explanatory variable for disparities in AAs; the crude relative risk of acute rejection in AAs was reduced by 46% when including tacrolimus variability in modeling and reduced by 40% for graft loss. Conclusions These data demonstrate that intrapatient tacrolimus variability is strongly associated with acute rejection in AAs and graft loss in all patients. Tacrolimus variability is a significant explanatory variable for disparities in AA recipients.