Potential influence of interleukin-6 -174G/C gene polymorphism on kidney graft function and tacrolimus dose requirements: five-year follow-up

Abstract

1. Introduction The study aimed to investigate the influence of interleukin (IL)-6 -174 G/C gene polymorphism on graft function (defined as estimated glomerular filtration rate, eGFR), as well as on the tacrolimus (Tac) pharmacokinetics during the five years after kidney transplantation. 2. Methods The study included 115 Caucasian kidney transplant recipients on Tac-based immunosuppression. The patients were followed between 6 and 60 post-transplantation months. Interleukin-6 and CYP3A5 genotyping were performed. 3. Results Patients carrying the IL-6 -174GG genotype had lower eGFR values compared to the patients with the IL-6 -174GC and −174CC genotypes at the 12th, 48th and 60th post-transplantation months. The linear regression analysis indicated that eGFR at the 6th post-transplantation month and IL-6 -174 G/C polymorphism are independent predictors of eGFR values in the late post-transplantation period. The IL-6 -174GG genotype carriers had lower dose-adjusted trough concentration (C0/D) of Tac compared to the IL-6 C allele carriers during the entire observation period (except at the 24th month), while this effect was independent of the CYP3A5 genotype within three years post-transplantation. 4. Conclusion Interleukin-6 genotyping could be an additional tool to categorise patients towards the risk of graft deterioration in the long-term post-transplantation period. The IL-6 genotyping could be supportive in genotype-guided dosing of Tac.