Abstract
The immature preterm kidney is likely to be vulnerable to acute kidney injury (AKI). However, the biomarkers currently used for AKI are not sensitive or specific and are also inadequate for the timely detection of AKI in preterm infants. The objectives of this study were to identify novel urinary biomarkers of AKI using proteomic techniques, and to verify and validate that the candidates can serve as early predictive biomarkers for AKI. In total, 1,810 proteins were identified in the discovery phase. Among those proteins, 174 were selected as the 1st targeted proteins. A total of 168 proteins were quantified, and the levels of 6 were significantly increased in the AKI group in the verification phase. Using a clinical assay, the results were confirmed and validated using samples of the first urine after birth from the biorepository. Finally, enzyme-linked immunosorbent assays revealed that the levels of annexin A5, neutrophil gelatinase-associated lipocalin (NGAL), and protein S100-P were significantly higher in the samples of the first urine from patients with AKI than in those from patients without AKI. In conclusion, urinary annexin A5, NGAL and protein S100-P levels are promising biomarkers for early, accurate prediction of AKI in preterm infants.
Highlights
The immature preterm kidney is likely to be vulnerable to acute kidney injury (AKI)
Among the 37 infants who were enrolled in the cohort study, 5 patients were identified as having AKI after ibuprofen treatment
This study described the identification, verification and validation of urinary biomarkers for AKI in extremely preterm infants
Summary
The immature preterm kidney is likely to be vulnerable to acute kidney injury (AKI). the biomarkers currently used for AKI are not sensitive or specific and are inadequate for the timely detection of AKI in preterm infants. The objectives of this study were to identify novel urinary biomarkers of AKI using proteomic techniques, and to verify and validate that the candidates can serve as early predictive biomarkers for AKI. Urinary annexin A5, NGAL and protein S100-P levels are promising biomarkers for early, accurate prediction of AKI in preterm infants. Measuring SCr frequently in small infants is not advised because of a concern about the amount of blood loss due to multiple blood samplings Regardless of these limitations, SCr still remains the standard tool used for the diagnosis of AKI because of the lack of appropriate biomarkers for AKI in neonates. The objectives of this study were 1) to identify novel urinary biomarkers of AKI using proteomic techniques, and 2) to verify and validate that the discovered candidates are early predictive biomarkers for AKI in extremely preterm infants
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