Use of pharmacogenomics in pediatric renal transplant recipients
- PMID: 25741362
- PMCID: PMC4332348
- DOI: 10.3389/fgene.2015.00041
Use of pharmacogenomics in pediatric renal transplant recipients
Abstract
Transplant recipients receive potent immunosuppressive drugs in order to prevent graft rejection. Therapeutic drug monitoring is the current approach to guide the dosing of calcineurin inhibitors, mammalian target of rapamycin inhibitors (mTORi) and mofetil mycophenolate. Target concentrations used in pediatric patients are extrapolated from adult studies. Gene polymorphisms in metabolizing enzymes and drug transporters such as cytochromes CYP3A4 and CYP3A5, UDP-glucuronosyl transferase, and P-glycoprotein are known to influence the pharmacokinetics and dose requirements of immunosuppressants. The implications of pharmacogenomics in this patient population is discussed. Genetic information can help with achieving target concentrations in the early post-transplant period, avoiding adverse drug reactions and drug-drug interactions. Evidence about genetic studies and transplant outcomes is revised.
Keywords: GWAS; acute rejection; adverse reactions; drug metabolism; genotype; graft survival; immunosuppression; pharmacogenomics.
Similar articles
-
Effect of CYP3A and ABCB1 single nucleotide polymorphisms on the pharmacokinetics and pharmacodynamics of calcineurin inhibitors: Part II.Clin Pharmacokinet. 2010 Apr;49(4):207-21. doi: 10.2165/11317550-000000000-00000. Clin Pharmacokinet. 2010. PMID: 20214406 Review.
-
The pharmacogenetics of immunosuppression for organ transplantation: a route to individualization of drug administration.Am J Pharmacogenomics. 2003;3(5):291-301. doi: 10.2165/00129785-200303050-00001. Am J Pharmacogenomics. 2003. PMID: 14575518 Review.
-
Treatment strategies in pediatric solid organ transplant recipients with calcineurin inhibitor-induced nephrotoxicity.Pediatr Transplant. 2006 Sep;10(6):721-9. doi: 10.1111/j.1399-3046.2006.00577.x. Pediatr Transplant. 2006. PMID: 16911497 Review.
-
Impact of CYP3A4*1B and CYP3A5*3 polymorphisms on the pharmacokinetics of cyclosporine and sirolimus in renal transplant recipients.Ann Transplant. 2012 Jul-Sep;17(3):36-44. doi: 10.12659/aot.883456. Ann Transplant. 2012. PMID: 23018254
-
Effects of genetic polymorphisms on the pharmacokinetics of calcineurin inhibitors.Am J Health Syst Pharm. 2006 Dec 1;63(23):2340-8. doi: 10.2146/ajhp060080. Am J Health Syst Pharm. 2006. PMID: 17106006 Review.
Cited by
-
A pediatric perspective on genomics and prevention in the twenty-first century.Pediatr Res. 2020 Jan;87(2):338-344. doi: 10.1038/s41390-019-0597-z. Epub 2019 Oct 2. Pediatr Res. 2020. PMID: 31578042 Review.
-
The Value of Pharmacogenomics for White and Indigenous Americans after Kidney Transplantation.Pharmacy (Basel). 2023 Aug 8;11(4):125. doi: 10.3390/pharmacy11040125. Pharmacy (Basel). 2023. PMID: 37624080 Free PMC article.
-
Significant Effects of Renal Function on Mycophenolic Acid Total Clearance in Pediatric Kidney Transplant Recipients with Population Pharmacokinetic Modeling.Clin Pharmacokinet. 2023 Sep;62(9):1289-1303. doi: 10.1007/s40262-023-01280-0. Epub 2023 Jul 26. Clin Pharmacokinet. 2023. PMID: 37493886
-
CYP3A5 genotype affects time to therapeutic tacrolimus level in pediatric kidney transplant recipients.Pediatr Transplant. 2019 Aug;23(5):e13494. doi: 10.1111/petr.13494. Epub 2019 May 24. Pediatr Transplant. 2019. PMID: 31124575 Free PMC article.
-
Pediatric Nephrology in Primary Care: The Forest for the Trees.Front Public Health. 2015 Oct 6;3:227. doi: 10.3389/fpubh.2015.00227. eCollection 2015. Front Public Health. 2015. PMID: 26501050 Free PMC article. No abstract available.
References
-
- de Jonge H., Elens L., de Loor H., van Schaik R. H., Kuypers D. R. (2014). The CYP3A4*22 C>T single nucleotide polymorphism is associated with reduced midazolam and tacrolimus clearance in stable renal allograft recipients. Pharmacogenomics J. [Epub ahead of print]. 10.1038/tpj.2014.49 - DOI - PubMed
Publication types
LinkOut - more resources
Full Text Sources
Other Literature Sources