Pharmacotherapy · 2026
Association of Human Leucocyte Antigen with Tacrolimus Pharmacokinetics in Renal Transplant Patients.
СтатьяНазвание и аннотация: Перевод в очереди
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Hemani Rashmi J, Joreja Amit S, Shete Nitiraj B, Srivastava Ratika, Soni Shailesh M, Gang Shishir D, Konnur Abhijit M, Hegde Umapati N, Patel Hardik B, Mukhopadhyay Banibrata N, Raval Manan A, Pandey Sachchida Nand
Аннотация
INTRODUCTION: 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.
MATERIAL AND METHODS: 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.
RESULT: 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.
CONCLUSION: Our data suggest that HLA alleles influence the PK of Tac and affect graft survival in renal transplant patients.
MATERIAL AND METHODS: 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.
RESULT: 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.
CONCLUSION: Our data suggest that HLA alleles influence the PK of Tac and affect graft survival in renal transplant patients.