Increased ferritin levels are associated with incident diabetes after kidney transplantation: A prospective cohort study.

Aim: Iron is known to play a role in glucose homeostasis, and diabetes is highly prevalent in patients with iron overload. Here, we investigated whether ferritin and hepcidin (as parameters of iron status) are associated with the development of post-transplant diabetes in kidney transplant recipients, a population in which around 10 % is known to have high iron status.

Methods: Prospective data from the TransplantLines Insulin Resistance and Inflammation Biobank and Cohort Study from the University Medical Center Groningen, the Netherlands were evaluated, involving stable adult kidney transplant recipients > 1 year after transplantation. Associations between ferritin and hepcidin levels, as markers of iron status, and incident post-transplant diabetes were analyzed by multivariable Cox regression models, followed by the exploration of potential clinical cut-offs of ferritin levels related to the risk of post-transplant diabetes.

Results: Of the included 443 kidney transplant recipients (age 50 ± 12 years, 44 % women, median 6.1 [3.0 - 12.1] years after transplantation), 65 kidney transplant recipients (15 %) developed post-transplant diabetes during a median follow-up of 9.6 [6.3 - 10.2] years. In contrast to hepcidin levels, ferritin levels were significantly associated with incident post-transplant diabetes, independent of adjustment for potential confounders (HR per 50 µg/l, 1.08; 95 % CI 1.02 - 1.14). When analyzing specific clinical cut-offs of ferritin levels, kidney transplant recipients with a ferritin > 500 µg/l (n=40) had more than twice the risk of developing post-transplant diabetes, compared to kidney transplant recipients with ferritin < 100 µg/l (HR, 2.81; 95 % CI 1.04 - 7.55).

Conclusions: Increased levels of ferritin are independently associated with a higher risk of post-transplant diabetes in kidney transplant recipients. Especially, kidney transplant recipients with ferritin levels > 500 µg/l, seem susceptible to the development of post-transplant diabetes over time.