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^th, 48^th and 60^th post-transplantation months. The linear regression analysis indicated that eGFR at the 6^th 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 24^th 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.