Abstract
Introduction: Chronic kidney disease (CKD) after liver transplantation (LT) is a major clinical problem that appears to be associated with non-genetic, as well as genetic determinants. The use of the nephrotoxic calcineurin inhibitors (CNIs) cyclosporine A (CsA) and tacrolimus (Tac) is considered to be an important risk factor for CKD after LT. However, it is unknown why certain patients are more prone to suffer from the nephrotoxic effects of these agents than others. We therefore studied the influence of single-nucleotide polymorphisms (SNPs) in the genes of the CNI-metabolizing enzyme CYP3A5 and the CNI- transporting ABCB1, in addition to clinical variables, on the development of CKD after LT. Methods: In a retrospective study, the pre- and post-transplantation clinical variables were correlated by multivariate Cox-regression analysis to the development of CKD [defined as a glomerular filtration rate < 60 mL/min/1.73m2] in 399 LT-recipients that were transplanted in our center between 1986 and 2009. In addition, the CYP3A5 6986A>G and ABCB1 3435C>T SNPs were determined in both recipients and their respective donors to study the influence of genetics on the development of CKD. Results: After a median follow up of 9.2 years (95%-CI: 8.1-10.2) CKD developed in 195 patients (48.8%). Cox proportional hazard analysis indicated that that an increased risk of CKD was associated with increasing age at the time of LT, female gender [hazard ratio (HR) 1.6, p< 0.01], use of CsA rather than Tac (HR 1.9, p< 0.01), Caucasian ethnicity rather Black ethnicity (HR 2.7, p< 0.01) and the period of LT (with a lower risk in the more recent era). The investigated SNPs in ABCB1 and CYP3A5 (or combinations thereof) were not correlated with the development of CKD. Conclusion: An individual's risk to develop CKD after LT is associated with several clinical factors but is not explained by genetic variations in recipient or donor CYP3A5 or ABCB1. Genotyping of LT recipients is therefore unlikely to aid in preventing CKD.
Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
