BACKGROUND: Changes in kidney function, as assessed by early and even small variations in serum creatinine (ΔsCr), affect survival in adults following cardiac surgery but such associations have not been reported in infants. This raises the question of the adequate assessment of kidney function by early ΔsCr in infants undergoing cardiac surgery. METHODOLOGY: The ability of ΔsCr within 2 days of surgery to assess the severity of kidney injury, accounted for by the risk of 30-day mortality, was explored retrospectively in 1019 consecutive neonates and infants. Patients aged ≤ 10 days were analyzed separately because of the physiological improvement in glomerular filtration early after birth. The Kml algorithm, an implementation of k-means for longitudinal data, was used to describe creatinine kinetics, and the receiver operating characteristic and the reclassification methodology to assess discrimination and the predictive ability of the risk of death. RESULTS: Three clusters of ΔsCr were identified: in 50% of all patients creatinine decreased, in 41.4% it increased slightly, and in 8.6% it rose abruptly. Mortality rates were not significantly different between the first and second clusters, 1.6% [0.0-4.1] vs 5.9% [1.9-10.9], respectively, in patients aged ≤ 10 days, and 1.6% [0.5-3.0] vs 3.8% [1.9-6.0] in older ones. Mortality rates were significantly higher when creatinine rose abruptly, 30.3% [15.1-46.2] in patients aged ≤ 10 days, and 15.1% [5.9-25.5] in older ones. However, only 41.3% of all patients who died had an abrupt increase in creatinine. ΔsCr improved prediction in survivors, but not in patients who died, and did not improve discrimination over a clinical mortality model. CONCLUSIONS: The present results suggest that a postoperative decrease in creatinine represents the normal course in neonates and infants with cardiac surgery, and that early creatinine variations lack sensitivity for the assessment of the severity of kidney injury.