A prognostic value of early urinary biomarkers NGAL and IL-18 in critically ill children: A 10-year literature review

Abstract

Introduction. Acute kidney injury (AKI) is a life-threatening syndrome caused by a sudden and rapidly progressing impairment of renal function. It is a common and complicated clinical entity among hospitalized children, occurring in 2%-4.5% of children treated in a pediatric intensive care unit. Mortality among such patients remains high (from 8% to 89%) despite improving patient care and technical possibilities. The stage of renal damage is a reversible process, and its timely detection would prevent the progression of renal damage and thus reduce pediatric mortality rates. Therefore, modern medicine necessitates the identification of novel AKI biomarkers that would correlate with renal cell damage and could be detected earlier than a rise in serum creatinine (sCr). Neutrophil gelatinase-associated lipocalin (NGAL) and interleukin 18 (IL-18) are one of such early markers of AKI. Aim. To carry out a literature review of studies on changes in NGAL and IL-18 levels in the urine of critically ill patients and to determine a prognostic value of these biomarkers in the detection of renal injury and impact on disease outcomes. Material and methods. This literature review includes the publications of biomedical studies assessing early biomarkers of AKI in urine (uNGAL or uIL-18) of critically ill children, published in English during the 10-year period. Search for publication was performed in the PubMed database. Results. Analysis included 10 studies that investigated early biomarkers of AKI (NGAL or IL-18) in urine of critically ill children and compared them with sCr. Among the biomedical studies analyzed in our literature review, 9 measured the NGAL level in urine or both in urine and serum, while 2measured IL-18 in urine. It was determined that uNGAL and uIL- 18 were good early diagnostic biomarkers of AKI, which increased 48 h earlier than Cr in serum (P<0.005). The meta-analysis carried out by Haase et al. showed that uNGAL predicted the development of AKI better in critically ill children than in adults (OR, 25.4; ROC, 0.930 vs. OR, 10.6; ROC, 0.782). Three studies reported that the uNGAL level in study populations with AKI directly depended on disease severity and AKI degree (P<0.005). Four studies found that uNGAL and one study that uIL- 18 are good predictive factors of mortality (P<0.005). Conclusions. uNGAL and uIL-18 are early predictive biomarkers of AKI in critically ill children. uNGAL and uIL-18 level correlated well with disease severity and are independent predictive biomarkers of mortality.