El-sadek AE, et al. - Sixty critically ill neonates in NICUs were randomized to group 1 (cases) of candidates fulfilling the acute kidney injury (AKI) diagnostic criteria of neonatal Kidney Disease Improving Global Outcome, group 2 not fulfilling the criteria and in 1:1 ratio and the 3rd group of thirty age and gender matching healthy controls in order to contrast the ability of plasma cystatin C and renal resistive index (RRI) to early prognosticate AKI in critically ill neonates. During the 1st day of incubation, in comparison with the other two groups, group 1 showed a significantly high mean cystatin C level. Among all groups, serum creatinine and RRI were insignificantly distinctive. The only independent risk factors within critically ill infants were applying regression analysis to prognosticate AKI in critically ill kids as soon as possible, greater plasma Cystatin C and lower eGFR Cystatin. In conclusion, in critically ill neonates who developed AKI, plasma Cystatin C rose 48 hours prior to both RRI and serum creatinine, thus, it is more secure in prognosticating AKI in critically ill infants as that of serum creatinine and RRI.