Logo Annals of Transplantation Logo Annals of Transplantation Logo Annals of Transplantation

29 June 2012

Tacrolimus-induced nephrotoxicity and genetic variability: A review

Violette M.G.J. Gijsen, Parvaz Madadi, Marie-Pierre Dube, Dennis A. Hesselink, Gideon Koren, Saskia N. de Wildt

DOI: 10.12659/AOT.883229

Ann Transplant 2012; 17(2): 111-121


Background: Calcineurin inhibition (CNI) is the mainstay of immunosuppressant therapy for most solid organ transplant patients. High tacrolimus levels are related with acute nephrotoxicity, but the relationship with chronic toxicity is less clear. Variation in disposition of tacrolimus is associated with genetic variation in CYP3A5. Hence, could genetic variation in CYP3A5 or other genes involved in tacrolimus disposition and effect be associated with a risk for tacrolimus-induced nephrotoxicity? To perform a review of the literature and to identify if genetic variation in CYP3A5 or other genes involved in tacrolimus disposition or effect may be associated with tacrolimus-induced nephrotoxicity and/or renal dysfunction in solid organ transplant recipients. Material/Methods: Pubmed/Medline, Embase and Google were searched from their inception till November 8th 2010 with the search terms ‘tacrolimus’, ‘genetics’, and ‘nephrotoxicity’ or ‘renal dysfunction’. References of relevant articles were screened as well. Results: We identified 13 relevant papers. In kidney recipients, associations between donor ABCB1, recipient CCR5 genotype and tacrolimus-induced nephrotoxicity were found. CYP3A5 genotype studies in kidney recipients yielded contradictory results. In liver recipients, a possible association between recipient ACE, CYP3A5, ABCB1 and CYP2C8 genetic polymorphisms and tacrolimus-induced nephrotoxicity was suggested. In heart recipients, TGF-β genetic polymorphisms were associated with tacrolimus-induced nephrotoxicity. The quality of the studies varied considerably. Conclusions: Limited evidence suggests that variation in genes involved in pharmacokinetics (ABCB1 and CYP3A5) and pharmacodynamics (TGF-β, CYP2C8, ACE, CCR5) of tacrolimus may impact a transplant recipients’ risk to develop tacrolimus-induced nephrotoxicity across different transplant organ groups.

Keywords: Pharmacogenetics, Transplant, Tacrolimus, nephrotoxicity, CYP3A5, ABCB1, TGF-β

Add Comment 0 Comments

In Press

06 Feb 2024 : Case report  

Successful Sequential Liver and Isolated Intestine Transplantation for Mitochondrial Neurogastrointestinal ...

Ann Transplant In Press; DOI: 10.12659/AOT.941881  

12 Feb 2024 : Original article  

No Prognostic Impact of Graft-to-Recipient Weight Ratio on Hepatocellular Carcinoma Recurrence Following Li...

Ann Transplant In Press; DOI: 10.12659/AOT.942767  

21 Feb 2024 : Original article  

Use of LCP-Tacrolimus (LCPT) in Kidney Transplantation: A Delphi Consensus Survey of Expert Clinicians

Ann Transplant In Press; DOI: 10.12659/AOT.943498  

Most Viewed Current Articles

05 Apr 2022 : Original article  

Impact of Statins on Hepatocellular Carcinoma Recurrence After Living-Donor Liver Transplantation

DOI :10.12659/AOT.935604

Ann Transplant 2022; 27:e935604

12 Jan 2022 : Original article  

Risk Factors for Developing BK Virus-Associated Nephropathy: A Single-Center Retrospective Cohort Study of ...

DOI :10.12659/AOT.934738

Ann Transplant 2022; 27:e934738

22 Nov 2022 : Original article  

Long-Term Effects of Everolimus-Facilitated Tacrolimus Reduction in Living-Donor Liver Transplant Recipient...

DOI :10.12659/AOT.937988

Ann Transplant 2022; 27:e937988

15 Mar 2022 : Case report  

Combined Liver, Pancreas-Duodenum, and Kidney Transplantation for Patients with Hepatitis B Cirrhosis, Urem...

DOI :10.12659/AOT.935860

Ann Transplant 2022; 27:e935860

Your Privacy

We use cookies to ensure the functionality of our website, to personalize content and advertising, to provide social media features, and to analyze our traffic. If you allow us to do so, we also inform our social media, advertising and analysis partners about your use of our website, You can decise for yourself which categories you you want to deny or allow. Please note that based on your settings not all functionalities of the site are available. View our privacy policy.

Annals of Transplantation eISSN: 2329-0358
Annals of Transplantation eISSN: 2329-0358