Low tacrolimus (FK) trough concentrations have been associated with higher risk of acute rejection, particularly within African-American (AA) kidney transplant recipients; less is known about intra-patient FK concentration variability and its impact on racial disparities.

Methods: Ten-year, single-center, longitudinal cohort study of kidney transplant (KTX) recipients. Intra-patient FK variability was assessed using the coefficient of variation (%CV) measured before the clinical event and a comparable time period in those without events. Pediatrics, non-FK/MMF regimens, and non-renal transplants were excluded. Standard univariate tests and multivariable Cox regression models were used to analyze data.

Results: Between 2005 and 2010, 1,590 KTX recipients were included (53.9% AA) with follow up through 2015; 57,451 levels were utilized to assess intra-patient FK %CV (37±25 FK levels/patient). Overall, the intra-patient FK %CV was higher in AAs vs. non-AAs (48±15% vs. 44±13%, p<0.001). For acute rejection, there was significant effect modification by race; AAs with rejection had substantially higher FK %CV (54% vs 45%, p<0.001); this was not the case in non-AAs (44% vs 43%, p=0.5751). For graft loss, FK %CV was higher in both AAs (53% vs. 46%, p<0.001) and non-AAs (48% vs. 43%, p<0.001), when compared to those without graft loss, respectively (Figure). Cox regression demonstrated that FK %CV reduced disparities in AAs for acute rejection by 11% and for graft loss by 5% (Table). In fully adjusted models that included FK %CV and mean FK levels, AA race was no longer a significant risk factor for acute rejection (aHR 1.26, 0.88-1.81) or graft loss (aHR 0.98, 0.71-1.35).

Conclusion: These data demonstrate that intra-patient tacrolimus variability is strongly associated with acute rejection in AAs and with graft loss in all patients. Further, adjusting for tacrolimus variability appreciably reduces outcome disparities in AA KTX recipients.

CITATION INFORMATION: Taber D, Su Z, Posadas A, Gebregziabher M, Egede L, Dubay D, McGillicuddy J, Bratton C, Nadig S, Chavin K, Baliga P. Tacrolimus Trough Concentration Variability and Disparities in African American Kidney Transplantation. Am J Transplant. 2017;17 (suppl 3).

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