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Clinical Impact of the Adaptation of Initial Tacrolimus Dosing to the CYP3A5 Genotype After Kidney Transplantation: Systematic Review and Meta-Analysis of Randomized Controlled Trials

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Abstract

Objective

The aim of this systematic review and meta-analysis was to compare the clinical outcomes between genotype-guided and conventional tacrolimus doses in kidney transplantation patients.

Materials and Methods

We performed a comprehensive literature search of the PubMed, EMBASE, and Cochrane databases from the date of inception to 26 February 2020. References of the retrieved articles were also reviewed and any further relevant studies were included. The search terms included ‘tacrolimus’, ‘cytochrome P-450 CYP3A’, ‘polymorphism, genetic’, ‘genomics’, ‘genome’, ‘genotype’, ‘genes’, ‘alleles’, and ‘pharmacogenetics’.

Results

Our study showed that the genotype-guided group included an increased proportion of patients with tacrolimus concentrations in the therapeutic range at steady state (risk ratio [RR] 1.40, 95% confidence interval [CI] 1.14–1.72, p = 0.001; high quality), with a trend for achieving therapeutic concentrations earlier compared with those in the conventional group. However, there was no statistical difference in the incidence of delayed graft function (RR 1.98, 95% CI 0.92–1.76, p = 0.12; moderate quality), incidence of acute rejection (RR 1.00, 95% CI 0.64–1.55, p = 1.00; moderate quality), incidence of graft survival censored for death (RR 1.02, 95% CI 0.98–1.06, p = 0.37; moderate quality), and incidence of adverse effects (AEs).

Conclusions

Although the genotype-guided group had a higher proportion of patients within the targeted concentration and less median time to achieve the therapeutic range, the clinical endpoints, including delayed graft function, acute rejection, graft survival censored for death, and AEs were similar in both groups. All in all, evidence suggested there was no utility in pharmacogenetics for tacrolimus based on the cytochrome P450 (CYP) 3A5 genotype. Studies with Chinese and African American populations are needed due to the frequency of genetic polymorphisms of CYP3A5. Furthermore, a dosing algorithm that includes demographic and clinical factors plus multiple genetic variants should be added for consideration, and may optimize early tacrolimus exposure.

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Acknowledgements

We thank all authors of the included studies for their wonderful work.

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Authors and Affiliations

  1. Department of Pharmacy, Beijing Chao-Yang Hospital, Capital Medical University, 8 Gongren Tiyuchang Nanlu, Chaoyang District, Beijing, China

    Hui Yang, Yiqi Sun, Xiaojia Yu & Lihong Liu

  2. Department of Urology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China

    Xiaopeng Hu, Wei Wang & Xiaodong Zhang

Authors
  1. Hui Yang
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  2. Yiqi Sun
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  3. Xiaojia Yu
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  4. Xiaopeng Hu
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  5. Wei Wang
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  7. Lihong Liu
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Corresponding author

Correspondence to Lihong Liu.

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Funding

This research did not receive any specific grants from funding agencies in the public, commercial, or not-for-profit sectors.

Conflicts of Interest

Hui Yang, Yiqi Sun, Xiaojia Yu, Xiaopeng Hu, Wei Wang, Xiaodong Zhang, and Lihong Liu declare no conflicts of interest.

Ethical Approval

This was a systematic review and meta-analysis based on previously published articles, therefore ethical approval was not required.

Consent to participate

This was a systematic review and meta-analysis based on previously published articles, therefore consent to participate was not required.

Consent for publication

This was a systematic review and meta-analysis based on previously published articles, therefore consent for publication was not required.

Availability of data and material

The datasets used or analyzed during the current study are available from the corresponding author on reasonable request.

Code availability

Not applicable.

Author Contributions

HY and LHL designed the experiments. HY, YS, XY, XH, WW, and XZ collected and analyzed the data. HY wrote the article, which was reviewed by all authors.

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Yang, H., Sun, Y., Yu, X. et al. Clinical Impact of the Adaptation of Initial Tacrolimus Dosing to the CYP3A5 Genotype After Kidney Transplantation: Systematic Review and Meta-Analysis of Randomized Controlled Trials. Clin Pharmacokinet 60, 877–885 (2021). https://doi.org/10.1007/s40262-020-00955-2

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  • DOI: https://doi.org/10.1007/s40262-020-00955-2

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