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The tacrolimus metabolism affect post-transplant outcome mediating acute rejection and delayed graft function:

Han Ro1, Jong Cheol Jeong2, Jin Min Kong3

  • 1Department of Internal Medicine, Gil Hospital, Gachon University, Incheon, Korea.

Transplant International : Official Journal of the European Society for Organ Transplantation
|October 24, 2020
PubMed

Insights

Slow tacrolimus metabolism in kidney transplant recipients is linked to better graft function and reduced rejection. Fast metabolism, however, can negatively impact outcomes through acute rejection and delayed graft function.

Area of Science:

  • Nephrology
  • Immunology
  • Pharmacogenomics

Background:

  • Tacrolimus is crucial for kidney transplantation (KT) but has a narrow therapeutic index.
  • The relationship between tacrolimus metabolism rate and KT outcomes requires large-scale, multi-center investigation.

Purpose of the Study:

  • To investigate the association between tacrolimus metabolism rate and kidney transplant outcomes.
  • To analyze the impact of tacrolimus metabolism on estimated glomerular filtration rate (eGFR), acute rejection (AR), and interstitial fibrosis and tubular atrophy (IFTA).

Main Methods:

  • Utilized Korean Organ Transplantation Registry (KOTRY) data from 3456 kidney transplant recipients.
  • Defined tacrolimus metabolism rate as blood trough concentration (C0) divided by daily dose (D).
  • Grouped patients into fast, intermediate, or slow metabolizers based on C0/D at 6 months post-transplant.

Main Results:

  • Slow metabolizers showed a significantly higher adjusted eGFR (2.7 ml/min/1.73 m²), less AR (OR 0.744), and less IFTA (OR 0.606) at 6 months.
  • Fast tacrolimus metabolism negatively impacted 6-month post-KT eGFR, mediated by AR and delayed graft function (DGF).
  • AR and DGF were identified as significant mediators in the relationship between fast tacrolimus metabolism and eGFR.

Conclusions:

  • Slow tacrolimus metabolism is associated with improved kidney transplant outcomes, including better graft function and reduced rejection.
  • Understanding tacrolimus metabolism rates can help personalize immunosuppressive therapy to optimize kidney transplant success.
Keywords:
kidney transplantationpharmacogeneticstacrolimus metabolism

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