Association of Human Leucocyte Antigen with Tacrolimus Pharmacokinetics in Renal Transplant Patients

Tacrolimus (Tac or FK-506) is an immunosuppressive agent that inhibits T-cell activation and proliferation. It has a narrow therapeutic index and shows inter-patient variabilities in its plasma concentration. Human Leucocyte Antigen (HLA) plays a major role in immune regulation and function. Tac inhibits the T-cells, and HLA antigens are expressed in T-cells. The objective of this study was to determine the role of the HLA Class I (HLA-A, HLA-B, and HLA-C) and Class II (HLA-DRB1, HLA-DQB1, and HLA-DQA1) in influencing Tac PK among renal transplant patients.

This study included HLA genotyping data of 462 renal transplant patients. Tacrolimus blood trough concentration/dose (Co/D) was calculated on day 7 and months 1, 3, 6, and 12 post-transplantation, and the association with HLA alleles was studied. Furthermore, biopsy-proven toxicity, rejection, and pathological events were evaluated for their association with HLA alleles.

One-way ANOVA analysis showed that HLA-B*51:01 and HLA-C*16:02 were significantly associated with Tac Co/D at multiple time points, with a significance level of p < 0.05. In addition, HLA-DRB1*04:03 was associated with post-renal transplant toxicity [Hazard Ratio (HR) = 8.500, 95% Confidential Interval (CI) (1.517-47.619)] and pathological events [HR = 2.310, 95% CI (1.149-4.642)]. HLA-A*02:11 [HR = 3.530, 95% CI (1.074-11.601)], and HLA-DQB*03:01 [HR = 5.055, 95% CI (1.544-16.551)] were associated with high risk of transplant rejection.

Our data suggest that HLA alleles influence the PK of Tac and affect graft survival in renal transplant patients.