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 a frequent complication in critically ill neonates and is associated with adverse outcomes. Infants with congenital diaphragmatic hernia (CDH) are particularly vulnerable due to pulmonary hypoplasia, hemodynamic instability, and exposure to nephrotoxic agents. METHODS: We retrospectively analyzed 193 neonates with CDH treated at a tertiary referral center (2012-2021). AKI was graded using modified pediatric RIFLE (pRIFLE), neonatal KDIGO (nKDIGO), and CysC-based neonatal AKI (CyNA) criteria, disregarding the urine output criteria. Clinical variables included CDH severity, extracorporeal membrane oxygenation (ECMO) use, and sepsis. Associations with AKI were examined using multivariable logistic regression. RESULTS: AKI incidence varied significantly by definition (CyNA 82% > pRIFLE 78% > nKDIGO 56%; CyNA vs. pRIFLE/nKDIGO p = 0.028/p = 0.010). Moderate AKI was detected in 61% (CyNA), 38% (pRIFLE), and 26% (nKDIGO) of the cases. Severe AKI was detected in 42% (pRIFLE), 30% (nKDIGO), and 20% (CyNA) of the cases. Severe CyNA was significantly associated with in-hospital mortality (p = 0.003). The severity of AKI was associated with a stepwise increase in mortality (mild/moderate vs. severe, p < 0.01), as well as prolonged hospitalization, kidney replacement therapy, and hypertension at discharge. Independent risk factors for AKI included lower observed-to-expected lung-to-head ratio, sepsis, and ECMO. CONCLUSIONS: AKI is a frequent and clinically important complication in neonates with CDH and is strongly associated with overall disease severity, incidence of sepsis, and ECMO. Neonates with severe AKI have a higher mortality. CysC might serve as an additional biomarker for the detection of neonates with CDH and fatal outcome. Future studies should assess whether integrating both serum creatinine and CysC into AKI monitoring improves the early detection of neonates with CDH at risk of acute and chronic kidney disease.