Effect of CYP3A5 genotype on renal allograft recipients treated with tacrolimus

Transplant Proc. 2009 Jun;41(5):1557-61. doi: 10.1016/j.transproceed.2009.01.097.


Objective: Tacrolimus concentrations are associated with CYP3A5 genotype. The purpose of this study was to evaluate the outcomes and drug concentrations/doses among a posttransplant population with various CYP3A5 genotypes within 12 months.

Methods: Sixty seven kidney recipients receiving immunosuppression with tacrolimus + mycophenolate mofetil + prednisolone were grouped according to their CYP3A5 genotypes (*1/*1; *1/*3; *3/*3). The initial dose of tacrolimus (0.15 mg/kg/d) was adjusted according to achieve a target therapeutic window. All patients underwent a protocol biopsy at 1 month posttransplantation. We assayed serum creatinine and tacrolimus blood trough concentrations to calculate the concentration per dosage during follow-up. We also investigated the incidence of acute rejection episodes and the nephrotoxicity of tacrolimus according to the renal biopsy.

Results: There was no significant difference among serum creatinine concentrations. Tracrolimus blood concentrations showed a significant difference at day 7 and 1 month with no significant difference at 3, 6, or 12 months among the three groups. The CYP3A5*3/*3 group showed the largest concentration per dosage (C/D) and CYP3A5*1/*1, the smallest C/D. There was a significant difference among the three groups. The occurrence of an acute rejection episode within 3 months showed a significant difference among the three groups but not from 3 to 12 months after transplantation. Nephrotoxicity was greatest among the CYP3A5*3/*3 group.

Conclusion: CYP3A5 influenced the blood concentrations of tacrolimus. Our study suggested to choose the initial dosage according to the CYP3A5 genotype to obtain a better outcome and reduce the incidences of acute rejection episodes and nephrotoxicity.

MeSH terms

  • Adolescent
  • Adult
  • Cadaver
  • Child
  • Creatinine / blood
  • Cytochrome P-450 CYP3A / genetics*
  • Drug Therapy, Combination
  • Female
  • Genotype
  • Humans
  • Immunosuppressive Agents / blood
  • Immunosuppressive Agents / therapeutic use
  • Kidney Transplantation / immunology*
  • Kidney Transplantation / pathology
  • Kidney Tubules / pathology
  • Male
  • Middle Aged
  • Polymorphism, Genetic*
  • Tacrolimus / blood
  • Tacrolimus / therapeutic use*
  • Tissue Donors
  • Transplantation, Homologous
  • Young Adult


  • Immunosuppressive Agents
  • Creatinine
  • CYP3A5 protein, human
  • Cytochrome P-450 CYP3A
  • Tacrolimus