Tacrolimus Dose Requirement Based on the CYP3A5 Genotype in Renal Transplant Patients.

L. Qu, Z. Xie, H. Huang, H. Jiang, J. Chen, H. Jiang, H. Jiang, J. Chen, J. Chen, J. Chen.

Kidney Disease Center, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, China

Meeting: 2017 American Transplant Congress

Abstract number: D110

Keywords: Drug interaction, Kidney transplantation

Session Information

Session Name: Poster Session D: Kidney Immunosuppression: Novel Regimens and Drug Minimization

Session Type: Poster Session

Date: Tuesday, May 2, 2017

Session Time: 6:00pm-7:00pm

Presentation Time: 6:00pm-7:00pm

Location: Hall D1

Background The aim of the present study is to determine whether CYP3A5*A and CYP3A5*G genotype is a predictive index of tacrolimus dose requirement, and also the selection yardstick of tacrolimus or CsA treatment.

Methods We tested archival peripheral blood of 218 kidney recipients for CYP3A5 genotyping with PCR-SSP. The doses and blood concentrations of tacrolimus and CsA for recipients were measured at day7, 1st month, 3rd month, 6th month and 12th month after kidney transplantation.

Results 123 patients received tacrolimus treatment and 95 patients received CsA treatment after renal transplantation.

In the tacrolimus treatment group, the frequency of CYP3A5*AA, CYP3A5*AG, and CYP3A5*GG was 11/123, 47/123, 65/123 respectively. Genotype CYP3A5*GG was associated with low tacrolimus dose-adjusted concentration, showing a lower acute rejection rate compared to the CYP3A5*AA/AG group but with no significant difference p=0.154).The CYP3A5*GG group took shorter time to get the target therapeutic concentration and maintain a stable dose-adjusted concentration with lower tacrolimus expenses than the CYP3A5*AA/AG group.Tacrolimus dose-adjusted concentration at all these time points poses no significant effect on liver and graft function.In the CsA treatment group, the frequency of CYP3A5*AA and CYP3A5*AG was 9/95 and 34/95 respectively, including 16/43 patients switching to tacrolimus treatment after CsA treatment for several years. The frequency of CYP3A5*GG was 52/95, including 20/52 patients switching to tacrolimus treatment. There was no significant difference in the acute rejection rate between CYP3A5*AA/AG and CYP3A5*GG ( P=0.494). In the CYP3A5*AA/AG subgroup, the acute rejection rates were similar before and after treatment shift ( P=0.654) in the same patients. However, the acute rejection rate was lower after shift to tacrolimus treatment in CYP3A5*GG subgroup (7/20 vs. 2/20, P=0.127).

Conclusions. These results indicate that CYP3A5*AA/AG carriers need higher tacrolimus dose than CYP3A5*GG homozygote to achieve the target blood concentration. CYP3A5*GG carriers preferred to tacrolimus treatment and CYP3A5*AA/AG carriers preferred to CsA treatment depended on the incomes. CYP3A5 genotyping is a new approach to detecting tacrolimus dose requirement and a predictive index for the tacrolimus or CsA treatment selection in the kidney recipients.

CITATION INFORMATION: Qu L, Xie Z, Huang H, Jiang H, Chen J, Jiang H, Jiang H, Chen J, Chen J, Chen J. Tacrolimus Dose Requirement Based on the CYP3A5 Genotype in Renal Transplant Patients. Am J Transplant. 2017;17 (suppl 3).

To cite this abstract in AMA style:

Qu L, Xie Z, Huang H, Jiang H, Chen J, Jiang H, Jiang H, Chen J, Chen J, Chen J. Tacrolimus Dose Requirement Based on the CYP3A5 Genotype in Renal Transplant Patients. [abstract]. Am J Transplant. 2017; 17 (suppl 3). https://atcmeetingabstracts.com/abstract/tacrolimus-dose-requirement-based-on-the-cyp3a5-genotype-in-renal-transplant-patients/. Accessed November 22, 2024.

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