Abstract
BACKGROUND: Necrotizing enterocolitis (NEC) is a devastating gastrointestinal condition increasingly recognized to cause systemic complications, including acute kidney injury (AKI). However, the underlying mechanisms and variations in renal impairment remain largely unknown, and there is a lack of non-invasive imaging methods for detecting early kidney injury. METHODS: We evaluated kidney injury through a multimodal approach, using a neonatal rat model of experimental NEC. Plasma and renal tissue were analyzed for pro-inflammatory cytokines (TNF-α, IL-6, IL-1β) by ELISA. Histological analysis and immunofluorescence staining were used to identify renal abnormalities and expression of KIM-1 and NGAL. Photoacoustic imaging (PAI) was used to assess renal oxygenation and total hemoglobin as functional biomarkers of kidney injury. RESULTS: NEC pups showed significant elevations of systemic and renal cytokines, as well as increased expression of KIM-1 and NGAL in proximal tubules of the kidney. Histological examination further confirms the renal injury in the NEC pup kidneys. PAI demonstrated reduction in renal oxygen saturation, offering non-invasive physiological biomarker assessment of kidney damage. CONCLUSION: This study introduces PAI as a promising imaging modality for non-invasive evaluation of renal injury in NEC and characterizes AKI associated with NEC as an inflammatory and hypoxic response in the neonatal rat NEC model.