Comparison of Creatinine- and Cystatin C–Based Definitions of Acute Kidney Injury in Neonates with Congenital Diaphragmatic Hernia

Abstract Background Acute kidney injury (AKI) is increasingly recognized as a major complication in critically ill neonates and is associated with poor outcomes. Infants with congenital diaphragmatic hernia (CDH) are particularly at risk due to pulmonary hypoplasia, hemodynamic instability, and exposure to nephrotoxic agents. This study aimed to evaluate the incidence, severity, and risk factors of AKI in neonates with CDH using three different AKI definitions and to assess the diagnostic performance of Cystatin C (CysC) as a renal biomarker. Methods We retrospectively analyzed 193 neonates with CDH treated at a single tertiary referral center between 2012 and 2021. AKI was graded according to modified pediatric RIFLE (pRIFLE), neonatal KDIGO (nKDIGO), and CysC-based neonatal AKI (CyNA) criteria. Demographic and clinical treatment data were collected, including CDH severity and use of extracorporeal membrane oxygenation (ECMO). Associations between risk factors and AKI were evaluated using univariate and multivariate logistic regression models. Results AKI incidence ranged from 48–89% depending on the applied definition (CyNA > pRIFLE > nKDIGO). Severe AKI occurred in 21–35% of neonates. Mortality increased stepwise with AKI severity (4.5% − 32.4%; p < 0.01). Infants with AKI had significantly longer hospital stays, more frequent renal replacement therapy, and higher rates of hypertension at discharge. Independent risk factors for AKI included lower observed-to-expected lung-to-head ratio, clinical sepsis, and ECMO use. CysC was more sensitive than creatinine-derived AKI definitions in detecting AKI in general, and moderate AKI in particular. Conclusions AKI is a frequent and clinically significant complication in neonates with CDH, and strongly associated with disease severity, sepsis, and ECMO support. CysC enhances early AKI detection and may serve as a promising biomarker for long-term cardiovascular surveillance. Future studies could assess whether structured post-discharge monitoring incorporating CysC could improve early identification of infants at risk for chronic kidney and cardiovascular disease.