Potential Influence of Interleukin-6 -174G/C Gene Polymorphism on Kidney Graft Function and Tacrolimus Dose Requirements: Five-year Follow-up

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 12, 48 and 60 post-transplantation months. The linear regression analysis indicated that eGFR at the 6 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 (C/D) of Tac compared to the IL-6 C allele carriers during the entire observation period (except at the 24 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.