The overlooked subgroup: preterm neonates with elevated serum creatinine outside neonatal AKI criteria

Background: To characterize risks and outcomes of preterm neonates with elevated serum creatinine (SCr) not meeting acute kidney injury (AKI) criteria. Methods: This cohort study included neonates <31 weeks’ gestation admitted to a university hospital. Elevated SCr was defined as exceeding the 95th percentile for postnatal age without meeting standard AKI criteria in neonates <28 or 28–30 weeks. Perinatal/neonatal risks and discharge outcomes were compared among elevated SCr, SCr-AKI, and no SCr-AKI subgroups. Results: Among 810 infants, 156 had SCr-AKI, 623 had no SCr-AKI, and 31 had elevated SCr. Compared to no SCr-AKI, the elevated SCr subgroup had lower birthweight, higher rates of small-for-gestational-age, respiratory distress, hemodynamic instability, prolonged invasive ventilation, lower anthropometric z-scores, and higher mortality, despite similar gestational age. Compared to SCr-AKI, they had higher gestational age and higher rates of small-for-gestational-age, with similar mortality. Adjusted models showed elevated SCr (adjusted relative risk [aRR], 3.74) and SCr-AKI (aRR, 3.95) predicted higher mortality versus no SCr-AKI. Conclusion: Gestational age-specific SCr references are critical for identifying preterm neonates with elevated SCr levels outside AKI criteria, who face neonatal risks and distinct mortality outcomes. Impact statement: The risks and outcomes of preterm neonates with elevated serum creatinine (SCr) levels that do not meet Kidney Disease: Improving Global Outcomes (KDIGO) acute kidney injury (AKI) criteria require further investigation. These neonates have distinct exposure profiles compared to those with KDIGO SCr-AKI and a poorer prognosis than those without SCr-AKI. They also have higher mortality than neonates without SCr-AKI. Our findings highlight the importance of gestational age–specific SCr reference values in neonatal care to better identify at-risk preterm infants beyond KDIGO criteria, enabling early intervention and improved outcomes.