THE DIAGNOSTIC VALUE OF URINE GELATINASE-ASSOCIATED LIPOCALIN AS A BIOMARKER FOR ACUTE KIDNEY INJURY IN PRETERM INFANTS WITH HEMODYNAMICALLY SIGNIFICANT PATENT DUCTUS ARTERIOSUS
Authors: Obolonska O. , Borysova T. , Vakulenko V. , Obolonsky O. 
Published: February 2023

SummaryTimely diagnosis of acute kidney injury (AKI) is problematic due to difficulties in using the “Kidney Disease: Improving Global Outcomes (KDIGO) guideline” modified for neonates, requiring the search for non-invasive markers and their diagnostic capacity assessment. Preterm infants with hemodynamically significant patent ductus arteriosus (HSPDA) are highly vulnerable to developing AKI. Renal biomarker neutrophil gelatinase-associated lipocalin (NGAL) in urine enables diagnosis of AKI, although literature data on the possibility of its use are somewhat contradictory.The aim of this study was to identify diagnostic capacity of the renal biomarker NGAL in urine for the early diagnosis of AKI in preterm infants with HSPDA. Materials and methods A total of 29 preterm infants (gestational age 29-36 weeks) with HSPDA were examined at the Department of Anesthesiology and Neonatal Intensive Care on the first, third and tenth day. The patients were assigned to groups depending on the development of AKI: the AKI group with any degree of severity - 14 children, and the group without AKI - 15 children. To determine the influence of HSPDA size on the level of urine NGAL, the children were further divided based on ductal size: HSPDA diameter ≥ 2 mm - 11 children, and HSPDA diameter ≤ 2 mm - 18 children. The urine NGAL level was quantitatively measured using sandwich enzyme-linked immunosorbent assay according to the manufacturer's licensed instructions (ELISA Kit, 96, USA). The study has a positive conclusion of the biomedical ethics commission of the Dnipro State Medical University (protocol of the commission meeting No. 2 dated October 19, 2022)/ A set of statistical research methods was used to solve the tasks and check the initial assumptions, namely: for independent samples - the Mann-Whitney test, for dynamic assessment - the Wilcoxon signed rank test. The test for the normality of the distribution of quantitative samples was carried out using the Kolmogorov-Smirnov test. Statistical processing of the results was carried out using the software product STATISTICA 6.1® (StatSoft Inc., serial number AGAR909E415822FA). The work was carried out within the scope of complex research works of the Department of Propaedeutics of Children's Diseases and Pediatrics 2 of the Dnipro State Medical University "Development of criteria for early diagnosis and prediction of comorbid kidney damage in children with somatic and infectious diseases" (state registration number 0119U100836) execution 09.2019-12.2023.Results. In the group of children with AKI, the significant increase in the urine NGAL level was observed from the first to the tenth day. For example, the urine NGAL level was 2.2 times (p<0.002) and 2.4 times (p<0.001) increased on the third and tenth day, respectively, as compared to that on the first day, while in the group without AKI, urine NGAL level was 1.3 times (p<0.04) increased on the third day compared to that on the first day. On the tenth day, in the group without AKI, the urine NGAL level was increased by 1.6 times (p<0.007) compared to that on the first day and by 1.2 times (p<0.04) as compared to that on the third day. The data obtained were confirmed by the clear correlation between the urine NGAL level and the development of AKI. For instance, the urine NGAL level at the first day was significantly correlated with AKI on the third and on the fifth day: ρ=0.72, p<0.001 and ρ=0.75, p<0.001, respectively. On the third day, the urine NGAL level was also significantly correlated with AKI on the third and on the fifth day: ρ=0.65, p<0.001 and ρ=0.73, p<0.001, respectively. It was particularly important that the urine NGAL level on the first day was significantly correlated with the maximum stage of AKI: ρ=0.76, p<0.001.In preterm infants with HSPDA size > 2 mm, the urine NGAL level on the first day of life was 1.7 times higher than that in children with HSPDA ≤ 2 mm (p < 0.002). It was also observed on the third day as in preterm infants with HSPDA size > 2 mm, the urine NGAL level was 2.3 times higher than that in children with HSPDA ≤ 2 mm (p < 0.001). On the tenth day, there was a 2.3-fold higher urine NGAL level in the group with ductal diameter > 2 mm as compared to the group with ductal diameter ≤ 2 mm (p < 0.003). The correlation between the urine NGAL level and the size of HSPDA has been found to be quite revealing. Notably, on the first day, urine NGAL level was significantly correlated with the HSPDA size: ρ=0.66, p<0.001, and on the 10th day, it was significantly correlated with the ductal size on the first day: ρ=0.70, p<0.001. In addition, the urine NGAL level on the first day was significantly correlated with the HSPDA size on the third day: ρ=0.49, p<0.015. The significant correlation between the urine NGAL level on the third day with the ductal size on the third day has also been revealed: ρ=0.47, p<0.019. Finally, on the 10th day, the urine NGAL level was significantly correlated with the HSPDA size on the third day: ρ = 0.46, p < 0.022.Conclusions. The elevated urine NGAL level has been found to be a reliable marker of the AKI development in preterm infants with HSPDA: it was 1.7 times (p<0.001), 2.8 times (p<0.001) and 2.6 times (p<0.001) increased on day one, three and ten, respectively, in children with AKI in comparison with those examined without AKI. In preterm infants with HSPDA diameter of > 2 mm on the first day, the urine level of NGAL was significantly increased on the first, third and tenth day.