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Updated: May 20, 2026
08:38
Quantification of the Immunosuppressant Tacrolimus on Dried Blood Spots Using LC-MS/MS
Published on: November 8, 2015
Tacrolimus-induced nephrotoxicity and genetic variability: a review
Violette M G J Gijsen1, Parvaz Madadi, Marie-Pierre Dube
1Division of Clinical Pharmacology and Toxicology, Hospital for Sick Children, Toronto, Ontario, Canada.
Annals of Transplantation
|June 30, 2012
Summary
Genetic variations in genes like CYP3A5 and ABCB1 may influence the risk of tacrolimus-induced nephrotoxicity in organ transplant recipients. Further research is needed to clarify these genetic associations.
Area of Science:
- Pharmacogenomics
- Transplant Medicine
- Nephrology
Background:
- Calcineurin inhibitors (CNI), particularly tacrolimus, are essential immunosuppressants post-solid organ transplantation.
- While high tacrolimus levels link to acute nephrotoxicity, chronic effects and genetic influences are less understood.
- Genetic variations in drug-metabolizing enzymes like CYP3A5 affect tacrolimus disposition.
Purpose of the Study:
- To review existing literature on the association between genetic variations and tacrolimus-induced nephrotoxicity.
- To identify specific genes involved in tacrolimus disposition and effect that may influence renal toxicity risk.
Main Methods:
- A comprehensive literature search was conducted across PubMed/Medline, Embase, and Google up to November 2010.
- Search terms included 'tacrolimus', 'genetics', and 'nephrotoxicity' or 'renal dysfunction'.
- References from relevant articles were also screened.
Main Results:
- Thirteen studies were identified, revealing potential associations between genetic polymorphisms and nephrotoxicity in different transplant groups.
- In kidney recipients, donor ABCB1 and recipient CCR5 genotypes showed associations; CYP3A5 results were conflicting.
- In liver recipients, ACE, CYP3A5, ABCB1, and CYP2C8 polymorphisms were suggested; in heart recipients, TGF-β polymorphisms were linked to nephrotoxicity.
Conclusions:
- Limited evidence suggests that genetic variations in pharmacokinetic (e.g., ABCB1, CYP3A5) and pharmacodynamic genes (e.g., TGF-β, CYP2C8, ACE, CCR5) may influence tacrolimus-induced nephrotoxicity risk.
- These genetic factors appear to impact risk across various solid organ transplant recipients.
- Further investigation is warranted to solidify these pharmacogenetic associations.
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