Currently, there are no successful therapies proven to ameliorate acute kidney injury (AKI). AKI secondary to ischemia reperfusion injury (IRI) leads to increased morbidity and mortality. The role of iron sequestration throughout cardiac surgery remains unclear, however it may be an important modifier of renal ischemia reperfusion injury. The primary goal was to characterize iron regulatory pathways in a prospective observational cohort of adult cardiac surgery patients in the context of clinical AKI predictors and in relation to clinical prediction alone. The secondary goal was to evaluate potential proteins that may act as non-invasive biomarkers for the early detection of AKI, including urine hepcidin-25, serum ferritin, serum transferrin saturation (TSAT) and urine lactotransferrin. We found that urine hepcidin-25 at postoperative day 1 and serum ferritin and TSAT at 1 hour into cardiopulmonary bypass were independent predictors of AKI avoidance on multivariate analysis, enhancing clinical prediction alone.