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. 2022 Oct 26;11(21):6320.
doi: 10.3390/jcm11216320.

Comparison of Tacrolimus Intra-Patient Variability during 6-12 Months after Kidney Transplantation between CYP3A5 Expressers and Nonexpressers

Almas Nuchjumroon  1 , Somratai Vadcharavivad  1 , Wanchana Singhan  2 , Manorom Poosoonthornsri  3 , Wiwat Chancharoenthana  4 , Suwasin Udomkarnjananun  5 , Natavudh Townamchai  5 , Yingyos Avihingsanon  5 , Kearkiat Praditpornsilpa  5 , Somchai Eiam-Ong  5
Affiliations

Comparison of Tacrolimus Intra-Patient Variability during 6-12 Months after Kidney Transplantation between CYP3A5 Expressers and Nonexpressers

Almas Nuchjumroon et al. J Clin Med. .

Abstract

A high intra-patient variability (IPV) of tacrolimus exposure is associated with poor long-term kidney transplantation outcomes. To assess the influence of cytochrome P450 (CYP) 3A5 genetic polymorphisms on tacrolimus IPV, 188 clinically stable kidney transplant recipients, who had received an immediate-release tacrolimus-based immunosuppressive regimen, were enrolled in this retrospective cohort study. Genotyping of CYP3A5*3 (rs776746) was performed and 110 (58.5%) were identified as CYP3A5 expressers and 78 (41.5%) as nonexpressers. Whole blood tacrolimus concentrations were analyzed by chemiluminescent microparticle immunoassay. Dose-adjusted trough tacrolimus concentrations (C0/D) measured at months 6, 9, and 12 were used to determine IPV. There were no significant differences in the IPV estimated by the coefficient of variation, the IPV calculated by mean absolute deviation method, and the proportions of recipients with the IPV estimated by the coefficient of variation of 30% or more between CYP3A5 expressers and nonexpressers (p = 0.613, 0.686, and 0.954, respectively). Tacrolimus C0/D in CYP3A5 expressers was approximately half of those in nonexpressers, overall (p < 0.001). In both CYP3A5 expressers and nonexpressers, tacrolimus C0/D increased gradually from month 6 to month 12 (p = 0.021). There was no evidence that the CYP3A5 polymorphisms significantly influence tacrolimus IPV during the 6 to 12 months after kidney transplantation.

Keywords: CYP3A5; genetic polymorphism; immunosuppression; intra-patient variability; kidney transplantation; tacrolimus; therapeutic drug monitoring.

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Conflict of interest statement

The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.

Figures

Figure 1
Figure 1
Flow diagram of the inclusion and exclusion process.
Figure 2
Figure 2
Correlation of intra-patient variability of tacrolimus dose-adjusted trough concentrations estimated by coefficient of variation and intra-patient variability of tacrolimus dose-adjusted trough concentrations estimated by mean absolute deviation method (the solid line is the regression line; the dashed line represents the line of identity).
Figure 3
Figure 3
Box plots of dose-adjusted tacrolimus trough concentrations in CYP3A5 expressers and nonexpressers at months 6, 9, and 12 post-kidney transplantation (the circle is the value that exceeds the first quartile minus 1.5 times the interquartile range or the third quartile plus 1.5 times the interquartile range; the asterisk represents the value that exceeds the first quartile minus 3.0 times the interquartile range or the third quartile plus 3.0 times the interquartile range).
Figure 4
Figure 4
Frequency distributions of intra-patient variability of tacrolimus dose-adjusted trough concentrations estimated by coefficient of variation in CYP3A5 expressers and nonexpressers.
See this image and copyright information in PMC

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