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Acute kidney injury (AKI) occurs in approximately 30% of all infants hospitalized in the neonatal intensive care unit. About 40% of very low-birth-weight infants develop AKI, with an estimated mortality rate of 50% to 80%. Very low-birth-weight survivors have twice the risk of developing chronic renal disease later in life compared with their term counterparts. Current diagnostic modalities for AKI include serum creatinine and urine output; however, recent studies suggest that these measures are imprecise, as they may not change until 25% to 50% of renal function is lost. Urinary biomarkers may more accurately identify infants at risk for early AKI development. The purpose of this review is to discuss current research findings related to neonatal AKI risk factors, provide an overview of short- and long-term outcomes, describe innovative diagnostic approaches, and identify future research direction needed to improve prediction and intervention strategies associated with renal impairment.