Neutrophil Gelatinase-Associated Lipocalin (NGAL) as a Biomarker for Early Detection and Grading of Acute Kidney Injury in Critically Ill Children

Acute kidney injury (AKI) is a common and deadly consequence in critically unwell children, with incidence rates ranging from 5% to 50% depending on the underlying condition and severity of the illness. Early detection and treatment of AKI are critical for limiting the progression of chronic renal disease and lowering mortality. However, the current AKI diagnostic criteria, which are based on serum creatinine and urine output, have limitations in terms of sensitivity and specificity, particularly in children. As a result, there is an urgent need to investigate novel biomarkers capable of accurately predicting the onset and severity of AKI in critically unwell infants.

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In recent years, Neutrophil gelatinase-associated lipocalin (NGAL) has emerged as a promising biomarker for both adult and pediatric populations for the early diagnosis and grading of AKI. NGAL is a tiny protein that is rapidly produced in kidney tubules in response to ischemia or inflammation and eliminated in urine and plasma. Its levels are markedly raised in the early stages of AKI, typically before changes in serum creatinine or urine output are visible, according to several investigations. As a result, NGAL has the potential to improve AKI diagnosis and care in critically ill children. We will review the current literature on NGAL as a biomarker for AKI in critically ill children and discuss its clinical value, limits, and future research.

?NGAL has been studied for its diagnostic and prognostic utility in the early detection and grading of AKI in critically unwell children in several studies. It was found to have a high sensitivity (92%) and moderate specificity (74%), as defined by the Kidney Disease Improving Global Outcomes (KDIGO), in a systematic review and meta-analysis of 21 studies, including 2,490 children. NGAL had a receiver operating characteristic (ROC) area of 0.87, showing good discrimination.

?Neutrophil gelatinase-associated lipocalin (NGAL) has also been found to be an effective biomarker for predicting the severity and recovery of AKI. NGAL levels were considerably greater in children with stage 3 AKI in a study of 125 children with AKI and were related with longer hospital stays and increased #mortality. Another research of 80 children undergoing heart surgery discovered that NGAL levels were considerably greater at 24 hours after surgery in those with persistent AKI, defined as AKI lasting more than 7 days, and were predictive of renal recovery at 30 days.

?Other biomarkers for the early detection of AKI in critically ill children, such as kidney injury molecule-1 (KIM-1) and interleukin-18 (IL-18), have been compared to NGAL. A study of 105 children undergoing cardiopulmonary bypass surgery discovered that NGAL had a higher sensitivity for predicting AKI than KIM-1 and IL-18 and was related with a higher likelihood of renal replacement therapy and mortality.

?Despite the promising results of NGAL as an AKI biomarker, there are several barriers to its widespread use in clinical practice. First, there is a lack of established cut-off values for NGAL, which may lead to variation in interpretation and impede cross-study comparability. Second, several factors, like as age, gender, comorbidities, and medications, might influence NGAL levels, potentially limiting its specificity for AKI. Third, the cost and availability of NGAL tests may be impediments to their widespread usage in resource-constrained situations.

?Finally, NGAL appears to be a promising biomarker for the early detection and grading of AKI in critically ill children. NGAL has been shown in several trials to have strong diagnostic and prognostic accuracy and can provide useful information for clinical decision-making. More research is needed, however, to establish standardized cut-off values for NGAL, validate its clinical utility in various populations and settings, and investigate its potential for personalized medicine approaches.

: #aki #biomarkers #pediatrics #criticalcare #KDIGO #KIM1 #IL18 #diagnosis #prediction #prognosis #personalizedmedicine

References:

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1. Kaddourah A, Basu RK, Bagshaw SM, Goldstein SL; AWARE Investigators. Epidemiology of acute kidney injury in critically ill children and young adults. N Engl J Med. 2017;376(1):11-20.

2. Jetton JG, Boohaker LJ, Sethi SK, et al. Incidence and outcomes of neonatal acute kidney injury (AWAKEN): a multicentre, multinational, observational cohort study. Lancet Child Adolesc Health. 2017;1(3):184-194.

3. Krawczeski CD, Woo JG, Wang Y, et al. Neutrophil gelatinase-associated lipocalin concentrations predict development of acute kidney injury in neonates and children after cardiopulmonary bypass. J Pediatr. 2011;158(6):1009-1015.

4. Zappitelli M, Washburn KK, Arikan AA, et al. Urine neutrophil gelatinase-associated lipocalin is an early marker of acute kidney injury in critically ill children: a prospective cohort study. Crit Care. 2007;11(4):R84.

5. Mishra J, Dent C, Tarabishi R, et al. Neutrophil gelatinase-associated lipocalin (NGAL) as a biomarker for acute renal injury after cardiac surgery. Lancet. 2005;365(9466):1231-1238.

6. Devarajan P. Neutrophil gelatinase-associated lipocalin: a promising biomarker for human acute kidney injury. Biomark Med. 2010;4(2):265-280.

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7. Srisawat N, Murugan R, Lee M, et al. Plasma neutrophil gelatinase-associated lipocalin predicts recovery from acute kidney injury following community-acquired pneumonia. Kidney Int. 2011;80(5):545-552.

8. Haase M, Bellomo R, Devarajan P, et al. Accuracy of neutrophil gelatinase-associated lipocalin (NGAL) in diagnosis and prognosis in acute kidney injury: a systematic review and meta-analysis. Am J Kidney Dis. 2009;54(6):1012-1024.

9. Koyner JL, Bennett MR, Worcester EM, et al. Urinary cystatin C as an early biomarker of acute kidney injury following adult cardiothoracic surgery. Kidney Int. 2008;74(8):1059-1069.

10. Siew ED, Ware LB, Gebretsadik T, et al. Urine neutrophil gelatinase-associated lipocalin moderately predicts acute kidney injury in critically ill adults. J Am Soc Nephrol. 2009;20(8):1823-1832.

11. Endre ZH, Pickering JW, Walker RJ, et al. Improved performance of urinary biomarkers of acute kidney injury in the critically ill by stratification for injury duration and baseline renal function. Kidney Int. 2011;79(10):1119-1130.

12. Parikh CR, Devarajan P. New biomarkers of acute kidney injury. Crit Care Med. 2008;36(4 Suppl):S159-S165.

13. Liangos O, Perianayagam MC, Vaidya VS, et al. Urinary N-acetyl-beta-(D)-glucosaminidase activity and kidney injury molecule-1 level are associated with adverse outcomes in acute renal failure. J Am Soc Nephrol. 2007;18(3):904-912.

14. Doi K, Katagiri D, Negishi K, et al. Mild elevation of urinary biomarkers in prerenal acute kidney injury. Kidney Int. 2012;82(10):1114-1120.

15. Kashani K, Al-Khafaji A, Ardiles T, et al. Discovery and validation of cell cycle arrest biomarkers in human acute kidney injury. Crit Care. 2013;17(1):R25.

16. Molnar AO, Parikh CR, Siew ED, et al. Association between preoperative proteinuria and postoperative AKI in patients undergoing nephrectomy. Clin J Am Soc Nephrol. 2014;9(3):477-484.

17. Siew ED, Ikizler TA, Gebretsadik T, et al. Elevated urinary IL-18 levels at the time of ICU admission predict adverse clinical outcomes. Clin J Am Soc Nephrol. 2010;5(8):1497-1505.

18. Ronco C, Kellum JA, Haase M. Subclinical AKI is still AKI. Crit Care. 2012;16(3):313.

19. Garg AX, Devereaux PJ, Yusuf S, et al. Kidney function after off-pump or on-pump coronary artery bypass graft surgery: a randomized clinical trial. JAMA. 2014;311(21):2191-2198.

20. Kashani K, Cheungpasitporn W, Ronco C. Biomarkers of acute kidney injury: the pathway from discovery to clinical adoption. Clin Chem Lab Med. 2017;55(8):1074-1089.

21. Krawczeski CD. NGAL: a biomarker of acute kidney injury in children. Am J Kidney Dis. 2013;62(2):172-174.