Effects of CYP3A5 polymorphisms on tacrolimus pharmacokinetics in pediatric kidney transplantation: a systematic review and meta-analysis of observational studies

• Published in: World journal of pediatrics : WJP Vol. 13; no. 5; pp. 421 - 426
• Main Authors: Zong, Yi-Ping, Wang, Zi-Jie, Zhou, Wan-Li, Zhou, Wei-Min, Ma, Tie-Liang, Huang, Zheng-Kai, Zhao, Chun-Chun, Xu, Zhen, Tan, Ruo-Yun, Gu, Min
• Format: Journal Article
• Language: English
• Published: Hangzhou Childrens Hospital, Zhejiang University School of Medicine 01.10.2017; Department of Urology,The Affiliated Yixing Hospital of Jiangsu University, Yixing, China%Department of Urology, Nanjing Medical University First Affiliated Hospital, Nanjing, China%Department of Urology,The Affiliated Yixing Hospital of Jiangsu University, Yixing, China%Central Laboratory,The Affiliated Yixing Hospital of Jiangsu University, Yixing, China; Department of Urology, Nanjing Medical University First Affiliated Hospital, Nanjing, China
• Subjects: Child; Critical Care Medicine; Cytochrome P-450 CYP3A - genetics; Humans; Imaging; Immunosuppressive Agents - pharmacokinetics; Intensive; Kidney Transplantation; Maternal and Child Health; Medicine; Medicine & Public Health; Meta-Analysis; Observational Studies as Topic; Pediatric Surgery; Pediatrics; Polymorphism, Single Nucleotide; Radiology; Surgery; Tacrolimus - pharmacokinetics; meta-analysis; tacrolimus; kidney transplantation; pediatric; CYP3A5
• ISSN: 1708-8569; 1867-0687
• DOI: 10.1007/s12519-017-0035-4

Background CYP3A5 genetic polymorphisms have been reported to be strongly associated with the tacrolimus pharmacokinetics in adult kidney transplantation. However, there is no published meta-analysis in the influence of CYP3A5 variants on the requirements of the tacrolimus dose in pediatric renal-transplant recipients (RTRs). We wished to determine the effects of CYP3A5 polymorphisms on tacrolimus pharmacokinetics in pediatric RTRs. Methods A literature search was conducted to include relevant articles by searching PubMed, EMBASE and the Cochrane Central Register of Controlled Trials. Pharmacokinetic-associated parameters such as dose administration, as well as concentrations and dose-adjusted concentrations of tacrolimus were extracted and the meta-analysis undertaken. Results The meta-analysis involved four studies and one study series involving 268 pediatric RTRs. A significant difference was observed in the mean trough concentration/dose of tacrolimus between recipients carrying CYP3A5 * 3 /* 3 variants (referred to as "non-expressers") and those carrying CYP3A5 * 1 (referred to as "expressers") [standard mean difference (SMD)=-1.09, 95% confidence interval (CI): -1.92 to -0.25, P =0.011]. Moreover, significance was observed in the mean daily dose of tacrolimus between non-expressers and expressers in pediatric RTRs (SMD=0.44, 95% CI: 0.20 to 0.68, P <0.001). Conclusion Our meta-analysis identified a positive correlation between CYP3A5 genotypes and tacrolimus pharmacokinetics in pediatric RTRs.