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Influence of POR*28 Polymorphisms on CYP3A5*3-Associated Variations in Tacrolimus Blood Levels at an Early Stage after Liver Transplantation
 
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Volume 21
Issue 8
10.3390/ijms21082976
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Article

Donor CYP3A5 Gene Polymorphism Alone Cannot Predict Tacrolimus Intrarenal Concentration in Renal Transplant Recipients

by
Mengyu Zhang
1,
Soichiro Tajima
2,
Tomohiro Shigematsu
1,2,
Rao Fu
1,
Hiroshi Noguchi
3,
Keizo Kaku
3,
Akihiro Tsuchimoto
4,
Yasuhiro Okabe
3,
Nobuaki Egashira
1,2 and
Satohiro Masuda
2,5,6,*
1
Department of Clinical Pharmacology and Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan
2
Department of Pharmacy, Kyushu University Hospital, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan
3
Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan
4
Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan
5
Department of Pharmacy, International University of Health and Welfare Narita Hospital, 852 Hatakeda, Narita 286-0124, Japan
6
Department of Clinical Pharmacy, Faculty of Pharmaceutical Sciences, International University of Health and Welfare, 2600-1 Kita-kanemaru, Otawara 324-8501, Japan
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2020, 21(8), 2976; https://doi.org/10.3390/ijms21082976
Received: 28 March 2020 / Revised: 20 April 2020 / Accepted: 22 April 2020 / Published: 23 April 2020
(This article belongs to the Special Issue Molecular Mechanisms and Biomarkers in Drug-Induced Organ Injury)
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Abstract

CYP3A5 gene polymorphism in recipients plays an important role in tacrolimus blood pharmacokinetics after renal transplantation. Even though CYP3A5 protein is expressed in renal tubular cells, little is known about the influence on the tacrolimus intrarenal exposure and hence graft outcome. The aim of our study was to investigate how the tacrolimus intrarenal concentration (Ctissue) could be predicted based on donor CYP3A5 gene polymorphism in renal transplant recipients. A total of 52 Japanese renal transplant patients receiving tacrolimus were enrolled in this study. Seventy-four renal biopsy specimens were obtained at 3 months and 1 year after transplantation to determine the donor CYP3A5 polymorphism and measure the Ctissue by liquid chromatography-tandem mass spectrometry (LC-MS-MS). The tacrolimus Ctissue ranged from 52 to 399 pg/mg tissue (n = 74) and was weak but significantly correlated with tacrolimus trough concentration (C0) at 3 months after transplantation (Spearman, r = 0.3560, p = 0.0096). No significant relationship was observed between the donor CYP3A5 gene polymorphism and Ctissue or Ctissue/C0. These data showed that the tacrolimus systemic level has an impact on tacrolimus renal accumulation after renal transplantation. However, donor CYP3A5 gene polymorphism alone cannot be used to predict tacrolimus intrarenal exposure. This study may be valuable for exploring tacrolimus renal metabolism and toxicology mechanism in renal transplant recipients. View Full-Text
Keywords: tacrolimus; renal transplantation; intrarenal concentration; whole blood concentration; LC-MS/MS tacrolimus; renal transplantation; intrarenal concentration; whole blood concentration; LC-MS/MS
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MDPI and ACS Style

Zhang, M.; Tajima, S.; Shigematsu, T.; Fu, R.; Noguchi, H.; Kaku, K.; Tsuchimoto, A.; Okabe, Y.; Egashira, N.; Masuda, S. Donor CYP3A5 Gene Polymorphism Alone Cannot Predict Tacrolimus Intrarenal Concentration in Renal Transplant Recipients. Int. J. Mol. Sci. 2020, 21, 2976. https://doi.org/10.3390/ijms21082976

AMA Style

Zhang M, Tajima S, Shigematsu T, Fu R, Noguchi H, Kaku K, Tsuchimoto A, Okabe Y, Egashira N, Masuda S. Donor CYP3A5 Gene Polymorphism Alone Cannot Predict Tacrolimus Intrarenal Concentration in Renal Transplant Recipients. International Journal of Molecular Sciences. 2020; 21(8):2976. https://doi.org/10.3390/ijms21082976

Chicago/Turabian Style

Zhang, Mengyu, Soichiro Tajima, Tomohiro Shigematsu, Rao Fu, Hiroshi Noguchi, Keizo Kaku, Akihiro Tsuchimoto, Yasuhiro Okabe, Nobuaki Egashira, and Satohiro Masuda. 2020. "Donor CYP3A5 Gene Polymorphism Alone Cannot Predict Tacrolimus Intrarenal Concentration in Renal Transplant Recipients" International Journal of Molecular Sciences 21, no. 8: 2976. https://doi.org/10.3390/ijms21082976

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