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. 2017 Dec;101(12):2931-2938.
doi: 10.1097/TP.0000000000001840.

Tacrolimus Trough Concentration Variability and Disparities in African American Kidney Transplantation

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Free PMC article

Tacrolimus Trough Concentration Variability and Disparities in African American Kidney Transplantation

David J Taber et al. Transplantation. .
Free PMC article

Abstract

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.

Conflict of interest statement

DISCLOSURES

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Boxplots of tacrolimus variability (%CV), stratified by race and outcome (top: acute rejection; bottom: graft loss).
Figure 2
Figure 2
Estimated rejection-free survival (2A, 2B and 2C) and cumulative incidence of graft loss (2D, 2E and 2F) compared between non-AAs and AAs in iterative models. Models 2A and 2D are unadjusted (crude risk), models 2B and 2E are adjusted for tacrolimus variability (CV >40%) and models 2C and 2F are fully adjusted. *Adjusted for tacrolimus variability (CV >40%) and number of tacrolimus concentrations ^Adjusted for tacrolimus variability, number of tacrolimus concentrations, age, sex, weight, ESRD diagnosis, diabetes, time on dialysis, previous transplant, current PRA, HLA mismatches, cold ischemic time, living donor, donor sex, donor race, induction therapy and delayed graft function

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