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Purpose of Review <p>Therapeutic drug monitoring has been the gold standard of monitoring immunosuppression for the last few decades. Despite improvements in short term survival, long term survival post-transplant remains stagnant. Innovative approaches are needed to improve outcomes in solid organ transplant recipients. Given that individual differences in pharmacokinetics and pharmacodynamics of immunosuppression can lead to significant variation in efficacy and toxicity, the identification of single nucleotide polymorphisms that better predict individual response has become an area of interest. Early studies incorporating pharmacogenetic data, particularly CYP3A5 status, either presence of or into a genotype-guided algorithm for kidney transplant recipients, did not translate into differences in outcomes such as acute rejection and delayed graft function.</p> Recent Findings <p>We included 68 studies featuring adult and pediatric kidney, liver, lung and heart transplant recipients. Presence of CYP3A5 polymorphisms in adult liver and heart transplant recipients may increase the risk of acute rejection likely driven by longer time to therapeutic range. While incorporation of CYP3A5 status into a dosing algorithm may reduce rejection risk in kidney transplant recipients. ABCB1 polymorphism may predict rejection in liver, but not kidney transplant. Additional SNPs may be associated with increased risk of adverse effects and infection. Lung and pediatric data remain limited.</p> Summary <p>The incorporation of pharmacogenomic testing into transplant practice, although widely available, is still limited by potential costs and need for testing prior to transplant. The best supported use of pharmacogenomic data currently is the incorporation of CYP3A4/5 status into dosing algorithms with the goal of improved time to therapeutic range and avoidance of supratherapeutic levels. Incorporation of non-CYP3A4/5 enzyme and transporter polymorphisms and long-term impact on clinical outcomes remains to be elucidated. Additionally, the use of extended release tacrolimus in CYP3A5 expressors and impact on outcomes is another area to be explored.</p>

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Impact of Pharmacogenomics on Transplant Outcomes: Review of Recent Literature

  • 期刊论文

  • 发表日期：

    2026年2月3日

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  • Kristen D. Belfield,
  • Elizabeth A. Cohen,
  • Gianna Girone,
  • Hillary Kuzaro,
  • Jennifer E. Marvin,
  • Stephanie H. Stocker

摘要

Purpose of Review

Therapeutic drug monitoring has been the gold standard of monitoring immunosuppression for the last few decades. Despite improvements in short term survival, long term survival post-transplant remains stagnant. Innovative approaches are needed to improve outcomes in solid organ transplant recipients. Given that individual differences in pharmacokinetics and pharmacodynamics of immunosuppression can lead to significant variation in efficacy and toxicity, the identification of single nucleotide polymorphisms that better predict individual response has become an area of interest. Early studies incorporating pharmacogenetic data, particularly CYP3A5 status, either presence of or into a genotype-guided algorithm for kidney transplant recipients, did not translate into differences in outcomes such as acute rejection and delayed graft function.

Recent Findings

We included 68 studies featuring adult and pediatric kidney, liver, lung and heart transplant recipients. Presence of CYP3A5 polymorphisms in adult liver and heart transplant recipients may increase the risk of acute rejection likely driven by longer time to therapeutic range. While incorporation of CYP3A5 status into a dosing algorithm may reduce rejection risk in kidney transplant recipients. ABCB1 polymorphism may predict rejection in liver, but not kidney transplant. Additional SNPs may be associated with increased risk of adverse effects and infection. Lung and pediatric data remain limited.

Summary

The incorporation of pharmacogenomic testing into transplant practice, although widely available, is still limited by potential costs and need for testing prior to transplant. The best supported use of pharmacogenomic data currently is the incorporation of CYP3A4/5 status into dosing algorithms with the goal of improved time to therapeutic range and avoidance of supratherapeutic levels. Incorporation of non-CYP3A4/5 enzyme and transporter polymorphisms and long-term impact on clinical outcomes remains to be elucidated. Additionally, the use of extended release tacrolimus in CYP3A5 expressors and impact on outcomes is another area to be explored.