TY - JOUR
T1 - Donor cyp3a5 gene polymorphism alone cannot predict tacrolimus intrarenal concentration in renal transplant recipients
AU - Zhang, Mengyu
AU - Tajima, Soichiro
AU - Shigematsu, Tomohiro
AU - Fu, Rao
AU - Noguchi, Hiroshi
AU - Kaku, Keizo
AU - tsuchimoto, akihiro
AU - Okabe, Yasuhiro
AU - Egashira, Nobuaki
AU - Masuda, Satohiro
N1 - Funding Information:
Funding: This work was supported in part by Grants-in-Aid for Scientific Research (KAKENHI) from the Ministry of Education, Culture, Sports, Science, and Technology of Japan (MEXT) (grant numbers: 18H02588 to S.M and 18K06786 to S.T.).
Publisher Copyright:
© 2020 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2020/4/2
Y1 - 2020/4/2
N2 - 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.
AB - 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.
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U2 - 10.3390/ijms21082976
DO - 10.3390/ijms21082976
M3 - Article
C2 - 32340188
AN - SCOPUS:85083827616
SN - 1661-6596
VL - 21
JO - International Journal of Molecular Sciences
JF - International Journal of Molecular Sciences
IS - 8
M1 - 2976
ER -