Acute kidney injury (AKI) in the newborn is a common problem in the neonatal intensive care unit with many underlying factors such as asphyxia, respiratory distress syndrome (RDS), and urogenital anomalies. The aim of this study is to highlight possible risk factors and profile of neonates developing AKI in the Neonatal Intensive Care Unit (NICU) of Cairo University Pediatric Hospital. The study was carried out on 90 neonates (30 patients and 60 controls), among neonates admitted to NICU. The study was done over two months, from January 2015 to March 2015. Our study showed that sepsis was detected in 53.3%, prematurity in 46.67%, RDS in 43.3%, congenital heart disease in 20%, and hypoxic-ischemic encephalopathy in 6.67% of patients. Maternal illness and low body temperature were both significant risk factors of AKI in neonates. History of maternal illness, low body temperature, sepsis, prematurity, and respiratory distress can contribute to the development of AKI in neonates.