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Journal of Intensive Care and Emergency Medicine

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


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.

Key words: acute kidney injury, critically ill children, biomarkers, uNGAL, uIL-18.

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The functional renal reserve: the key to unlocking the role of biomarkers of AKI?


The Normal Glomerular Filtration Rate (GFR):

There is considerable variation between normal individuals with regard to renal size and the overall nephron mass which are determined by not only genetic predisposition but nutritional factors and indeed perinatal exposures. (1) Clearly these factors will influence the measured baseline renal characteristics. The most widely used measure of kidney function is the GFR. The glomerular filtration rate describes the volume of fluid filtered from the glomerular capillaries into the Bowman’s capsule per unit time. This is maintained by the difference in tone of the afferent and efferent hence the filtration rate is dependent on this pressure differential created through vasoconstriction of the input or afferent arteriole versus the lower blood pressure created by vasodilation of the output or efferent arteriole. It follows that when any solute is freely filtered and neither reabsorbed nor secreted by the kidneys then the GFR will equal the clearance rate of that solute. The GFR is calculated from the quantity of the substance in the urine that originated from a calculable volume of blood over unit time. Where the serum creatinine is measured this is expressed simply as:

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Fluid Therapy and Acute Kidney Injury: A Question of Balance?


Fluid therapy remains one of the fundamental treatment options available for patients with acute kidney injury. However, there remains debate over several aspects of this treatment with many questions unanswered. Firstly, how do we prescribe fluid in this group of patients? Secondly, what is the role of fluid therapy in patients with or at risk of developing acute kidney injury and thirdly, what role does fluid balance play, if any, in the development of acute kidney injury. The following narrative review will attempt to tie some of the aspects of the treatment of this devastating syndrome together and formulate an overall hypothesis for fluid management in acute kidney injury.

Key words: Acute kidney injury, glomerular filtration rate, fluid overload

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