Of all kidney transplants, half are still lost in the first decade after transplantation. Here, using genetics, we probed whether interleukin 6 (IL-6) could be a target in kidney transplantation to improve graft survival. Additionally, we investigated if a genetic risk score (GRS) based on IL6 and IL10 variants could improve prognostication of graft loss. In a prospective cohort study, DNA of 1271 donor-recipient kidney transplant pairs was analyzed for the presence of IL6, IL6R, IL10, IL10RA, and IL10RB variants. These polymorphisms and their GRS were then associated with 15-year death-censored allograft survival. The C|C-genotype of the IL6 polymorphism in donor kidneys and the combined C|C-genotype in donor-recipient pairs were both associated with a reduced risk of graft loss (p = .043 and p = .042, respectively). Additionally, the GRS based on IL6, IL6R, IL10, IL10RA, and IL10RB variants was independently associated with the risk of graft loss (HR 1.53, 95%-CI [1.32-1.84]; p < .001). Notably, the GRS improved risk stratification and prediction of graft loss beyond the level of contemporary clinical markers. Our findings reveal the merits of a polygenic IL-6-based risk score strengthened with IL-10- polymorphisms for the prognostication and risk stratification of late graft failure in kidney transplantation.

• Klíčová slova
• interleukins, kidney transplantation, long-term graft survival, polymorphisms,
• MeSH
• alografty MeSH
• interleukin-10 * genetika   MeSH
• interleukin-6 * genetika   MeSH
• ledviny MeSH
• lidé MeSH
• prospektivní studie MeSH
• rizikové faktory MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• interleukin-10 * MeSH
• interleukin-6 * MeSH