Donor CYP3A5 Gene Polymorphism Alone Cannot Predict Tacrolimus Intrarenal Concentration in Renal Transplant Recipients
Open Access
- 23 April 2020
- journal article
- research article
- Published by MDPI AG in International Journal of Molecular Sciences
- Vol. 21 (8), 2976
- https://doi.org/10.3390/ijms21082976
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.Funding Information
- Ministry of Education, Culture, Sports, Science and Technology (18H02588, 18K06786)
This publication has 43 references indexed in Scilit:
- Quantification of Tacrolimus and Three Demethylated Metabolites in Human Whole Blood Using LC–ESI–MS/MSTherapeutic Drug Monitoring, 2012
- CYP3A5 Genotype-Phenotype Analysis in the Human Kidney Reveals a Strong Site-Specific Expression of CYP3A5 in the Proximal Tubule in Carriers of the CYP3A5*1 AlleleDrug Metabolism and Disposition, 2012
- Effect of CYP3A and ABCB1 Single Nucleotide Polymorphisms on the Pharmacokinetics and Pharmacodynamics of Calcineurin Inhibitors: Part IIClinical Pharmacokinetics, 2010
- Donor Age and Renal P-Glycoprotein Expression Associate with Chronic Histological Damage in Renal AllograftsJournal of the American Society of Nephrology, 2009
- New Insights Into the Pharmacokinetics and Pharmacodynamics of the Calcineurin Inhibitors and Mycophenolic Acid: Possible Consequences for Therapeutic Drug Monitoring in Solid Organ TransplantationTherapeutic Drug Monitoring, 2009
- Haplotypic Structure of ABCB1/MDR1 Gene Modifies the Risk of the Acute Allograft Rejection in Renal Transplant RecipientsTransplantation, 2008
- Impact of MDR1 and CYP3A5 on the oral clearance of tacrolimus and tacrolimus-related renal dysfunction in adult living-donor liver transplant patientsPharmacogenetics and Genomics, 2008
- 1199G>A and 2677G>T/A polymorphisms of ABCB1 independently affect tacrolimus concentration in hepatic tissue after liver transplantationPharmacogenetics and Genomics, 2007
- Therapeutic Monitoring of Calcineurin Inhibitors for the NephrologistClinical Journal of the American Society of Nephrology, 2007
- Influence of CYP3A5 and MDR1 polymorphisms on tacrolimus concentration in the early stage after renal transplantationClinical Transplantation, 2005