BACKGROUND: Acute kidney injury (AKI) carries a large burden of morbidity and mortality. Early diagnosis may lead to better strategies of clinical care. Cardiac surgery involving cardiopulmonary bypass is associated with a significant incidence of AKI. The study objective was to determine whether or not preoperative fibroblast growth factor-23 (FGF23) levels differed among pediatric patients who did or did not develop AKI following cardiac surgery. METHODS: A nested case-control study was performed. FGF23 levels were measured pre- and post-operatively in 19 children without chronic kidney disease (CKD) who underwent cardiopulmonary bypass. Five patients developed AKI and 14 patients served as controls. RESULTS: FGF23 levels in patients who developed AKI following cardiac surgery were elevated above normal levels, both pre-operatively and post-operatively compared with those patients who did not develop AKI. Relative risk of developing AKI when the pre-operative FGF23 level was >86 RU/mL was 2.0 (p = 0.033). Preoperative FGF23 levels correlated with post-operative fluid gain (correlation coefficient 0.607, p = 0.0059). CONCLUSIONS: FGF23 may serve as a pre-operative prognostic indicator of the development of AKI following cardiopulmonary bypass surgery in pediatric patients without CKD. Identifying patients more likely to have AKI following surgery provides a means of achieving closer clinical management of AKI and fluid balance.