The Significance Of Urine Neutrophil Gelatinase-associated Lipocalin As An Early Diagnostic Marker In Critical Ill Children With Acute Kidney Injury

Background: Acute kidney injury(AKI) is one of the common diseases in pediatric intensive care unit(PICU) and the morbidity and mortality increase year by year.Neutrophil gelatinase-associated lipocalin(neutrophil gelatinase-associated lipocalin, NGAL) is a kind of 25 k D protein secreted by neutrophils and covalently bounded to the gelatinase.On physiological conditions,it expresse low concentrations in epithelial tissues and organs including the kidneys and reabsorbed by tubular.When acute tubular injury happen, NGAL begins to compand in great account and expresses significantly in blood and urine. There were reports which observed that NGAL could occur several times higher within 2h when AKI was diagnosed, and the levels were related with the severity of renal injury. Blood NGAL concentration increases earlier than Serum creatinine for a few days which could find AKI in time.There are reports finding that urine NGAL(u NGAL) can overcome the shortcomings of repeating collecting blood by invasive operation, but whether it could be used as early indicators to predict acute kidney injury, especially the key point such as sensitivity and specificity, yet to be evidence-based. Sepsis is an important cause of AKI in critically ill patients in ICU, and the level of NGAL can also increase in early period of infection.So how can we distinguish the NGAL elevation because of AKI or infection?Whether severe infections affect the specificity of NGAL predicting AKI is not clear.Objective:To evaluate the value of urine neutrophil gelatinase-associated lipocalin(u NGAL) with acute kidney injury of critically ill children in pediatric intensive care unit(PICU).Methods: Eighty critically ill children were enrolled in this study at PICU of Children's Hospital Affiliated to Shanghai Jiao Tong University from April to June 2013.They were continuously observed for 72 hours. According to pediatric RIFLE(p RIFLE)criteria for diagnosis of AKI, patients were divided into AKI group(15 cases) or non-AKI group(65 cases).Additionally,according to sepsis diagnostic criteria, patients were divided into sepsis group(31cases) or non-sepsis group(49 cases).The levels of serum creatinine and u NGAL were measured within 6hour, 24 th hour,48 th hour,72 th hour after admitted to PICU.The differences of u NGAL levels between AKI and non-AKI groups, sepsis without AKI and non-sepsis non-AKI groups, sepsis merged AKI and sepsis without AKI groups,sepsis groups and severe sepsis?sepsis shock groups were analysed. The sensitivity and specificity of u NGAL and serum creatinine for diagnosis of AKI at 48 th hour were evaluated by ROC curve.Results: 1.13 cases of sixty-five non-AKI children developed to AKI after admitted to PICU for 72 h,defined as new developed AKI group.2. The u NGAL levels in AKI group withthin 6hour, at 24 th hour,48 th hour,72 th hour were 863.00(696.00)(ng/ml) ? 700.50(580.00)(ng/ml) ? 365.50(285.00)(ng/ml) ?289.50(319.30)(ng/ml)respectively,while at the same timepoint in non-AKI group were20.00(106.00)(ng/ml), 20.00(85.30)(ng/ml), 20.00(101.00)(ng/ml), 20.00(36.00)(ng/ml). Obviously,the u NGAL levels in AKI group were significantly higher than those in non-AKI group(p<0.01).3. The u NGAL levels in new developed group withthin 6hour, at 24 th hour,48 th hour,72 th hour were 529.00(518.40)(ng/ml) ? 368.50(316.00)(ng/ml) ?308.00(394.00)(ng/ml)?424.50(313.50)(ng/ml),which were much higher than those in non-AKI group at each timing point. The Scr levels in new developed group withthin 6hour, at 24 th hour,48 th hour,72 th hour were 25.75±6.11(mmol/L) ?50.25±56.93(mmol/L)?45.13±17.88(mmol/L)and45.63±23.99(mmol/L), while at the same timepoint in non-AKI group were 23.45±8.95(mmol/L)?23.02±7.65(mmol/L)?21.26±8.14(mmol/L)and21.68±7.86(mmol/L).The comparision of Scr at 48 th hour was statistic difference.4. The u NGAL levels rise at early stage in sepsis without AKI group and down to normal gradually after 48 th hour,which were no statistically significant difference compared with non-sepsis non-AKI group.5. The u NGAL levels continue increasing in sepsis merged AKI group, and have significant differences comparing with sepsis without AKI group(p<0.01).6.The variation trend and elevated levels at each time point of u NGAL between sepsis and severe sepsis?sepsis shock were consistent,with no statisticant difference(p>0.05).7.The areas under ROC curve of u NGAL and serum creatinine at 48 th hour were 0.902(95%CI:0.801-1.004) and 0.801(95%CI:0.768-0.981) respectively.Conclusion: The level of u NGAL has earlier increase for 24 to 48 hours than that of serum creatinine in critically ill children,and it can also reflect the severity of AKI.Therefore it can be used as an early diagnostic biomarker for AKI in PICU.