Background: The majority of liver transplant recipients (LTR) receive tacrolimus (TAC) to prevent allograft rejection. Early establishment of therapeutic levels is imperative to efficacy. Several factors are known to influence TAC dose requirements, including recipient race. Black transplant recipients typically require higher doses to achieve comparable TAC levels as non-black individuals, a finding partly explained by pharmacogenetic variability in hepatic cytochrome P450 enzyme activity. This study explores if black donor race is also associated with higher TAC dose requirements in LTR.

Methods: A retrospective analysis on LTR transplanted between 1/2006 and 8/2014. All black and white recipients of livers from black or white donors, who were prescribed TAC and had at least 60-day graft survival, were included. After 60 days post-transplant, the first two consecutive TAC trough levels on a stable dose that were in therapeutic range per institution protocol were evaluated. Bivariate analyses were performed to determine the impact of donor and/or recipient race on TAC dose requirements, defined as a standardized weight-based-dose adjusted (mg/kg)/(ng/mL).

Results: This study evaluated 114 LTR in three separate analyses: by donor race (white vs. black donor (WD vs. BD)); by recipient race (white vs. black recipient (WR vs. BR)); and by donor/recipient race cohort (WD/WR vs. WD/BR, BD/WR, BD/BR). The majority (72%) of subjects were male. The median ages of recipients and donors were 54 and 42 years, respectively. The main findings are shown below. Recipients of black donor livers required 1.4-times more TAC to achieve comparable levels as recipients of white donors. Black recipients of black donor livers required 2.3-times more TAC compared to white recipients of white donor livers. As expected, black recipients required higher TAC doses overall, but this was not statistically significant. There were no differences in one-year patient or graft survival in any analysis.

Conclusions: These results suggest that liver donor race influences TAC dose requirements, regardless of recipient race. Donor race should be considered when selecting an initial tacrolimus dose post liver transplantation.

CITATION INFORMATION: Knorr J, Vidal J, Navarro V, Zaki R. Evaluating the Influence of Liver Donor and Recipient Race on Tacrolimus Dose Requirements. Am J Transplant. 2016;16 (suppl 3).

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