Perinatal risk factors associated with acute kidney injury severity and duration among infants born extremely preterm

Background: We evaluated time-varying perinatal risk factors associated with early (≤7 post-natal days) and late (>7 post-natal days) severe acute kidney injury (AKI) occurrence and duration. Methods: A secondary analysis of Preterm Erythropoietin Neuroprotection Trial data. We defined severe AKI (stage 2 or 3) per neonatal modified Kidney Disease: Improving Global Outcomes criteria. Adjusted Cox proportional hazards models were conducted with exposures occurring at least 72 h before severe AKI. Adjusted negative binomial regression models were completed to evaluate risk factors for severe AKI duration. Results: Of 923 participants, 2% had early severe AKI. In the adjusted model, gestational diabetes (adjusted HR (aHR) 5.4, 95% CI 1.1–25.8), non-steroidal anti-inflammatory drugs (NSAIDs) (aHR 3.2, 95% CI 1.0–9.8), and vancomycin (aHR 13.9, 95% CI 2.3–45.1) were associated with early severe AKI. Late severe AKI occurred in 22% of participants. Early severe AKI (aHR 2.5, 95% CI 1.1–5.4), sepsis (aHR 2.5, 95% CI 1.4–4.4), vasopressors (aHR 2.9, 95% CI 1.8–4.6), and diuretics (aHR 2.6, 95% CI 1.9–3.6) were associated with late severe AKI. Participants who had necrotizing enterocolitis or received NSAIDs had longer severe AKI duration. Conclusion: We identified major risk factors for severe AKI that can be the focus of future research. Impact statement: Time-dependent risk factors for severe acute kidney injury (AKI) and its duration are not well defined among infants born <28 weeks’ gestation. Over 1 in 5 infants born <28 weeks’ gestation experienced severe AKI, and this study identified several major time-dependent perinatal risk factors occurring within 72 h prior to severe AKI. This study can support efforts to develop risk stratification and clinical decision support to help mitigate modifiable risk factors to reduce severe AKI occurrence and duration.