Document Type : Original Article
Authors
- Madhusudhan Mahadevaiah 1, 2
- Murali Mohan Nidasale Thimmaiah 2
- Venu Sashank Yerramsetty 2
- Jeevan Kumar 2
- Ranjith Kumar 2
1 Emergency Physician, General Hospital, Nanjungud, Mysore, India
2 Department of Emergency Medicine, Vydehi Hospital College: Vydehi Institute of Medical Sciences , ajiv Gandhi University of Health Sciences (RGUHS), Bangalore, India
Abstract
Objective: To evaluate the predictive and diagnostic accuracy of neutrophil gelatinase-associated lipocalin (NGAL) in acute kidney injury (AKI) and also to predict the renal replacement therapy (RRT) using NGAL as a marker.
Methods: This prospective study was conducted among the patients admitted to intensive care units. Plasma samples were collected 24 hours after admission and NGAL was measured using Triage® NGAL test, a specific point of care test which is based on the mechanism of fluorescence immunoassay. The diagnostic accuracy of plasma NGAL (pNGAL) to predict AKI in critically ill patients of ICU was assessed by applying receiver operator curve (ROC) analysis and calculating the area under the curve (AUC).
Results: In this study, 100 patients with the mean age of 49.56 ± 19.2 years were included for the period of 18 months. The blood samples were withdrawn from the patients 24 and 44 hours after admission. Totally, 55% (n = 55) of ICU patients were diagnosed with AKI. Plasma NGAL level was significantly increased in AKI patients as compared to non-AKI patients (742.65 ± 734.72 vs. 255.62 ± 440.09 μg/L; P < 0.01). The sensitivity and specificity of NGAL for diagnosing AKI was 83.6% and 88.9%, respectively. The overall diagnostic accuracy was 86%. Diagnostic accuracy of NGAL for requirement of RRT was 51%.
Conclusion: Plasma NGAL is a reliable marker for patients with AKI in ICU, in case the cause of kidney injury is not known. In addition, NGAL also predicts the RRT need based on AKI severity.
Keywords
Main Subjects
2. Shapiro NI, Trzeciak S, Hollander JE, et al. The diagnostic accuracy of plasma neutrophil gelatinase-associated lipocalin in the prediction of acute kidney injury in emergency department patients with suspected sepsis. Ann Emerg Med 2010;56(1):52-59.e1. doi:10.1016/j.
annemergmed.2010.02.010.
3. Susantitaphong P, Cruz DN, Cerda J, Abulfaraj M, Alqahtani F, Koulouridis I, et al. World incidence of AKI: a
meta-analysis. Clin J Am Soc Nephrol 2013; 8(9): 1482-93.doi: 10.2215/cjn.00710113.
4. Hobson C, Ozrazgat-Baslanti T, Kuxhausen A, Thottakkara P, Efron PA, Moore FA, et al. Cost and mortality associated with postoperative acute kidney injury. Ann Surg 2015;261(6): 1207-14. doi: 10.1097/sla.0000000000000732.
5. Kellum JA, Chawla LS, Keener C, Singbartl K, Palevsky PM, Pike FL, et al. The effects of alternative resuscitation strategies on acute kidney injury in patients with septic shock. Am J Respir Crit Care Med 2016; 193(3): 281-7. doi:10.1164/rccm.201505-0995OC.
6. Ronco C, Ricci Z, De Backer D, Kellum JA, Taccone FS, Joannidis M, et al. Renal replacement therapy in acute kidney injury: controversy and consensus. Crit Care 2015;19(1): 146. doi:10.1186/s13054-015-0850-8.
7. Bhatt GC, Das RR. Early versus late initiation of renal replacement therapy in patients with acute kidney injury-a systematic review & meta-analysis of randomized controlled trials. BMC Nephrol 2017; 18(1): 78. doi: 10.1186/s12882-017-0486-9.
8. Sharfuddin AA, Molitoris BA. Pathophysiology of ischemic acute kidney injury. Nat Rev Nephrol 2011; 7(4): 189-200. doi: 10.1038/nrneph.2011.16.
9. Cai L, Rubin J, Han W, Venge P, Xu S. The origin of multiple molecular forms in urine of HNL/NGAL. Clin J Am Soc Nephrol 2010; 5(12): 2229-35. doi: 10.2215/cjn.00980110.
10. Borregaard N, Cowland JB. Neutrophil gelatinaseassociated lipocalin, a siderophore-binding eukaryoticprotein. Biometals 2006; 19(2): 211-5. doi: 10.1007/s10534-005-3251-7.
11. Xu S, Venge P. Lipocalins as biochemical markers of disease. Biochim Biophys Acta 2000; 1482(1-2): 298-307. doi:10.1016/s0167-4838(00)00163-1.
12. Mishra J, Mori K, Ma Q, Kelly C, Barasch J, Devarajan P. Neutrophil gelatinase-associated lipocalin: a novel early urinary biomarker for cisplatin nephrotoxicity. Am J Nephrol 2004; 24(3): 307-15. doi: 10.1159/000078452.
13. Wenners AS, Mehta K, Loibl S, Park H, Mueller B, Arnold N, et al. Neutrophil gelatinase-associated lipocalin (NGAL) predicts response to neoadjuvant chemotherapy and clinical outcome in primary human breast cancer. PLoS One 2012;7(10): e45826. doi: 10.1371/journal.pone.0045826.
14. McLean MH, Thomson AJ, Murray GI, Fyfe N, Hold GL, El- Omar EM. Expression of neutrophil gelatinase-associated lipocalin in colorectal neoplastic progression: a marker of malignant potential? Br J Cancer 2013; 108(12): 2537-41.doi: 10.1038/bjc.2013.264.
15. Mårtensson J, Bellomo R. The rise and fall of NGAL in acute kidney injury. Blood Purif 2014; 37(4): 304-10. doi:10.1159/000364937.
16. Devarajan P. Emerging urinary biomarkers in the diagnosis of acute kidney injury. Expert Opin Med Diagn 2008; 2(4): 387-98. doi: 10.1517/17530059.2.4.387.
17. Antonucci E, Lippi G, Ticinesi A, Pigna F, Guida L, Morelli I, et al. Neutrophil gelatinase-associated lipocalin (NGAL): a promising biomarker for the early diagnosis of acute
kidney injury (AKI). Acta Biomed 2014; 85(3): 289-94.
18. Cruz DN, de Cal M, Garzotto F, Perazella MA, Lentini P, Corradi V, et al. Plasma neutrophil gelatinase-associated lipocalin is an early biomarker for acute kidney injury in an adult ICU population. Intensive Care Med 2010; 36(3):444-51. doi: 10.1007/s00134-009-1711-1.
19. Endre ZH, Pickering JW, Walker RJ, Devarajan P, Edelstein CL, Bonventre JV, 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): 1119-30. doi: 10.1038/ki.2010.555.
20. Bellomo R, Ronco C, Kellum JA, Mehta RL, Palevsky P. Acute renal failure - definition, outcome measures, animal models, fluid therapy and information technology needs:the Second International Consensus Conference of the Acute Dialysis Quality Initiative (ADQI) Group. Crit Care 2004; 8(4): R204-12. doi: 10.1186/cc2872.
21. Levey AS, Stevens LA, Schmid CH, Zhang YL, Castro AF 3rd, Feldman HI, et al. A new equation to estimate glomerular filtration rate. Ann Intern Med 2009; 150(9): 604-12. doi:10.7326/0003-4819-150-9-200905050-00006.
22. Soto K, Papoila AL, Coelho S, Bennett M, Ma Q, Rodrigues B, et al. Plasma NGAL for the diagnosis of AKI in patients admitted from the emergency department setting. Clin J Am Soc Nephrol 2013; 8(12): 2053-63. doi: 10.2215/cjn.12181212.
23. 23.Khan BD, Munir M, Khan F, Naqvi SM. Comparison of urine with plasma neutrophil gelatinase– associated lipocalin in detecting acute kidney injury after cardiopulmonary bypass surgery. Pak Armed Forces MedJ 2013; 63(2): 179-83.
24. Yamashita T, Doi K, Hamasaki Y, Matsubara T, Ishii T, Yahagi N, et al. Evaluation of urinary tissue inhibitor of metalloproteinase-2 in acute kidney injury: a prospective observational study. Crit Care 2014; 18(6): 716. doi:10.1186/s13054-014-0716-5.
25. Dai X, Zeng Z, Fu C, Zhang S, Cai Y, Chen Z. Diagnostic value of neutrophil gelatinase-associated lipocalin, cystatin C, and soluble triggering receptor expressed on myeloid cells-1 in critically ill patients with sepsis-associated acute kidney injury. Crit Care 2015; 19(1): 223. doi: 10.1186/s13054-015-0941-6.
26. Md Ralib A, Mat Nor MB, Pickering JW. Plasma Neutrophil Gelatinase-Associated Lipocalin diagnosed acute kidney injury in patients with systemic inflammatory disease and sepsis. Nephrology (Carlton) 2017; 22(5): 412-9. doi:10.1111/nep.12796.
27. Hjortrup PB, Haase N, Treschow F, Møller MH, Perner A. Predictive value of NGAL for use of renal replacement therapy in patients with severe sepsis. Acta Anaesthesiol Scand 2015; 59(1): 25-34. doi: 10.1111/aas.12427.
28. Tecson KM, Erhardtsen E, Eriksen PM, Gaber AO, Germain M, Golestaneh L, et al. Optimal cut points of
plasma and urine neutrophil gelatinase-associated lipocalin for the prediction of acute kidney injury among critically ill adults: retrospective determination and clinical validation of a prospective multicentre study. BMJ Open 2017; 7(7):e016028. doi: 10.1136/bmjopen-2017-016028.
29. Klein SJ, Brandtner AK, Lehner GF, Ulmer H, Bagshaw SM, Wiedermann CJ, et al. Biomarkers for prediction of renal replacement therapy in acute kidney injury: a systematic review and meta-analysis. Intensive Care Med 2018; 44(3):323-36. doi: 10.1007/s00134-018-5126-8.