Neutrophil gelatinase-associated lipocalin (NGAL) as biomarker of acute kidney injury: A review of the laboratory characteristics and clinical evidences

Clinical Chemistry and Laboratory Medicine

Volumn 50, Issue 9, 2012, Pages 1505-1517

  Clerico, Aldo ^a   Galli, Claudio ^b   Fortunato, Antonio ^c   Ronco, Claudio ^c  

^a SCUOLA SUPERIORE SANT ANNA   (Italy)

^b ABBOTT DIAGNOSTICS   (Italy)

^c SAN BORTOLO HOSPITAL   (Italy)

Author keywords

Acute kidney injury; Creatinine; Neutrophil gelatinase associated lipocalin (NGAL); Renal disease; Renal function

Indexed keywords

BIOLOGICAL MARKER; CREATININE; GELATINASE B; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; NEUTROPHIL GELATINASE ASSOCIATED LIPOCALIN; SCATTER FACTOR;

ACUTE KIDNEY FAILURE; ASSAY; ASYMPTOMATIC DISEASE; BLOOD ANALYSIS; CALIBRATION; CELL DIFFERENTIATION; CELL PROLIFERATION; CLINICAL ASSESSMENT; CLINICAL DECISION MAKING; CLINICAL PRACTICE; COMPUTER ANALYSIS; COST BENEFIT ANALYSIS; COST UTILITY ANALYSIS; CREATININE BLOOD LEVEL; DELAYED GRAFT FUNCTION; DIAGNOSTIC ACCURACY; ENZYME LINKED IMMUNOSORBENT ASSAY; ETHNICITY; EVIDENCE BASED MEDICINE; GENDER; GLOMERULUS FILTRATION RATE; HEART FAILURE; HEART SURGERY; HEMOLYSIS; HUMAN; IMMUNOASSAY; IMMUNOBLOTTING; IN VITRO STUDY; INNATE IMMUNITY; INTENSIVE CARE UNIT; KIDNEY INJURY; KIDNEY TRANSPLANTATION; LABORATORY TEST; LEUKOCYTE COUNT; META ANALYSIS (TOPIC); MORTALITY; NEUTROPHIL; NONHUMAN; PATHOGENESIS; POINT OF CARE TESTING; PRIORITY JOURNAL; PROGNOSIS; PROTEIN BINDING; PROTEIN BLOOD LEVEL; PROTEIN DETERMINATION; PROTEIN EXPRESSION; PROTEIN FUNCTION; PROTEIN PROTEIN INTERACTION; PROTEIN STABILITY; PROTEIN STRUCTURE; PROTEIN URINE LEVEL; RANDOMIZED CONTROLLED TRIAL (TOPIC); REFERENCE VALUE; RENAL REPLACEMENT THERAPY; REVIEW; STANDARDIZATION; SYSTEMATIC REVIEW (TOPIC); URINALYSIS;

EID: 84867761385     PISSN: 14346621     EISSN: 14374331     Source Type: Journal    
DOI: 10.1515/cclm-2011-0814     Document Type: Review

References (87)

1. Ronco C, Haapio M, House AA, Anavekar N, Bellomo R. Cardiorenal sindrome. J Am Coll Cardiol 2008;52:1527-39.
2. Ronco C, McCullough P, Anker SD, Anand I, Aspromonte N, Bagshaw SM, et al. Cardio-renal syndromes: report from the consensus conference of the Acute Dialysis Quality Initiative. Eur Heart J 2010;31:703-11.
3. Coca SG, Peixoto AJ, Garg AX, Krumholz HM, Parikh CR. The prognostic importance of a small acute decrement in kidney function in hospitalized patients: a systematic review and metaanalysis. Am J Kidney Dis 2007;50:712-20.
4. Coca SG, Yusuf B, Shlipak MG, Garg AX, Parikh CR. Long-term risk of mortality and other adverse outcomes after acute kidney injury: a systematic review and meta-analysis. Am J Kidney Dis 2009;53:961-73.
5. McCullough PA, Haapio M, Mankad S, Zamperetti N, Massie B, Bellomo R, et al. Prevention of cardio-renal syndromes: workgroup statements from the 7th ADQI Consensus Conference. Nephrol Dial Transplant 2010;25:1777-84.
6. Bellomo R, Kellum JA, Ronco C. Defining acute renal failure: physiological principles. Intensive Care Med 2004;30:33-7.
7. Cruz DN, Goh CY, Palazzuoli A, Slavin L, Calabrò A, Ronco C, et al. Laboratory parameters of cardiac and kidney dysfunction in cardio-renal syndromes. Heart Fail Rev 2011;16:545-51.
8. Devarajan P. Neutrophil gelatinase-associated lipocalin: a promising biomarker for human acute kidney injury. Biomarkers Med 2010;4:265-80.
9. Flower DR, North AT, Attwood TK. Structure and sequence relationships in the lipocalins and related proteins. Protein Sci 1993;2:753-61.
10. Clifton MC, Corrent C, Strong RK. Siderocalins: siderophorebinding proteins of the innate immune system. Biometals 2009;22:557-64.
11. Borregaard N, Cowland JB. Neutrophil gelatinase-associated lipocalin, a siderophore-binding eukaryotic protein. Biometals 2006;19:211-5.
12. Devireddy LR, Gazin C, Zhu X, Green MR. A cell surface receptor for lipocalin 24p3 selectively mediates apoptosis and iron uptake. Cell 2005;123:1293-305.
13. Hvidberg V, Jacobsen C, Strong RK, Cowland JB, Moestrup SK, Borregaard N. The endocytic receptor megalin binds the iron transporting neutrophil- gelatinase-associated lipocalin with high affinity and mediates its cellular uptake. FEBS Lett 2005;579:773-7.
14. Schmidt-Ott KM, Mori K, Li JY, Kalandadze A, Cohen DJ, Devarajan P, et al. Dual action of neutrophil gelatinase-associated lipocalin. J Am Soc Nephrol 2007;18:407-13.
15. Flo TH, Smith KD, Sato S, Rodriguez DJ, Holmes MA, Strong RK, et al. Lipocalin 2 mediates an innate immune response to bacterial infection by sequestrating iron. Nature 2004;432:917-21.
16. Haase M, Devarajan P, Haase-Fielitz A, Bellomo R, Cruz DN, Wagener G, et al. The outcome of neutrophil gelatinase-associated lipocalin-positive subclinical acute kidney injury-a multicenter pooled analysis of prospective studies. J Am Coll Cardiol 2011;57:1752-61.
17. Xu SY, Carlson M, Engström A, Garcia R, Peterson CG, Venge P. Purification and characterization of a human neutrophil lipocalin (HNL) from the secondary granules of human neutrophils. Scand J Clin Lab Invest 1994;54:365-76.
18. Cowland JB, Borregaard N. Molecular characterization and pattern of tissue expression of the gene for neutrophil gelatinase-associated lipocalin from humans. Genomics 1997;45:17-23.
19. Mishra J, Dent C, Tarabishi R, Mitsnefes MM, Ma Q, Kelly C, et al. Neutrophil gelatinase-associated lipocalin (NGAL) as a biomarker for acute renal injury after cardiac surgery. Lancet 2005;365:1231-8.
20. Bachorzewska-Gajewska H, Malyszko J, Sitniewska E, Malyszko JS, Dobrzycki S. Neutrophil-gelatinase-associated lipocalin and renal function after percutaneous coronary interventions. Am J Nephrol 2006;26:287-92.
21. Dent CL, Ma Q, Dastrala S, Bennett M, Mitsnefes MM, Barasch J, et al. Plasma neutrophil gelatinase-associated lipocalin predicts acute kidney injury, morbidity and mortality after pediatric cardiac surgery: a prospective uncontrolled cohort study. Crit Care 2007;11:R127.
22. Cai L, Borowiec J, Xu S, Han W, Venge P. Assays of urine levels of HNL/NGAL in patients undergoing cardiac surgery and the impact of antibody configuration on their clinical performances. Clin Chim Acta 2009;403:121-5.
23. Stejskal D, Karpísek M, Humenanska V, Hanulova Z, Stejskal P, Kusnierova P, et al. Lipocalin-2: development, analytical characterization, and clinical testing of a new ELISA. Horm Metab Res 2008;40:381-5.
24. Huynh TK, Bateman DA, Parravicini E, Lorenz JM, Nemerofsky SL, Sise ME, et al. Reference values of urinary neutrophil gelatinase-associated lipocalin in very low birth weight infants. Pediatr Res 2009;66:528-32.
25. Pedersen KR, Ravn HB, Hjortdal VE, Nørregaard R, Povlsen JV. Neutrophil gelatinase-associated lipocalin (NGAL): validation of commercially available ELISA. Scand J Clin Lab Invest 2010;70:374-82.
26. Grenier FC, Ali S, Syed H, Workman R, Martens F, Liao M, et al. Evaluation of the ARCHITECT urine NGAL assay: Assay performance, specimen handling requirements and biological variability. Clin Biochem 2010;43:615-20.
27. Wagener G, Jan M, Kim M, Mori K, Barasch JM, Sladen RN, et al. Association between increases in urinary neutrophil gelatinase-associated lipocalin and acute renal dysfunction after adult cardiac surgery. Anesthesiology 2006;105:485-91.
28. NGAL Rapid ELISA kit (KIT 037). Information included in the commercial web site (http://www.ngal.com/).
29. Cavalier E, Bekaert AC, Carlisi A, Legrand D, Krzesinski JM, Delanaye P. Neutrophil gelatinase-associated lipocalin (NGAL) determined in urine with the Abbott Architect or in plasma with the Biosite Triage? The laboratory's point of view. Clin Chem Lab Med 2011;49:339-41.
30. Triage NGAL Test (REF 98400EU). Biosite, Product insert. Inverness Medical, 01/08/2009.
31. Ronco C, Cruz D, Noland B. Neutrophil gelatinase-associated lipocalin curve and neutrophil gelatinase associated lipocalin extended-range assay: a new biomarker approach in the early diagnosis of acute kidney injury and cardio-renal syndrome. Semin Nephrol 2012;32:121-8.
32. Delanaye P, Rozet E, Krzesinski JM, Cavalier E. Urinary NGAL measurement: biological variation and ratio to creatinine. Clin Chim Acta 2011;412:390.
33. Parikh CR, Devarajan P, Zappitelli M, Sint K, Thiessen-Philbrook H, Li S, et al. Postoperative biomarkers predict acute kidney injury and poor outcomes after pediatric cardiac surgery. J Am Soc Nephrol 2011;22:1737-47.
34. Koyner J, Bennett M, Worcester E, Ma Q, Raman J, Jeevanandam V, et al. Urinary cystatin C as an early biomarker of acute kidney injury following adult cardiothoracic surgery. Kidney Int 2008;74:1059-69.
35. Tuladhar SM, Puntmann VO, Soni M, Punjabi PP, Bogle RG. Rapid detection of acute kidney injury by plasma and urinary neutrophil gelatinase-associated lipocalin after cardiopulmonary bypass. J Cardiovasc Pharmacol 2009;53:261-6.
36. Haase-Fielitz A, Bellomo R, Devarajan P, Story D, Matalanis G, Dragun D, et al. Novel and conventional serum biomarkers predicting acute kidney injury in adult cardiac surgery - a prospective cohort study. Crit Care Med 2009;37:553-60.
37. Parikh CR, Coca SG, Thiessen-Philbrook H, Schlipak MG, Koyner JL, Wang Z, et al. Postoperative biomarkers predict acute kidney injury and poor outcomes after adult cardiac surgery. J Am Soc Nephrol 2011;22:1748-57.
38. Hirsch R, Dent C, Pfriem H, Allen J, Beekman RH, Ma Q, et al. NGAL is an early predictive biomarker of contrast-induced nephropathy in children. Pediatr Nephrol 2007;22:2089-95.
39. Malyszko J, Bachorzewska-Gajewska H, Poniatowski B, Malyyszko JS, Dobrzycki S. Urinary and serum biomarkers after cardiac catheterization in diabetic patients with stable angina and without severe chronic kidney disease. Ren Fail 2009;31:910-19.
40. Wheeler DS, Devarajan P, Ma Q, Harmon K, Monaco M, Cvijanovich N, et al. Serum neutrophil gelatinase-associated lipocalin (NGAL) as a marker of acute kidney injury in critically ill children with septic shock. Crit Care Med 2008;36:1297-303.
41. Cruz DN, de Cal M, Garzotto F, Perazella MA, Leitini P, Corradi V, et al. Plasma neutrophil gelatinase-associated lipocalin is an early biomarker for acute kidney injury in an adult ICU population. Int Care Med 2010;36:444-51.
42. Constantin J-M, Futier E, Perbet S, Roszyk L, Lautrette A, Gillard T, et al. Plasma neutrophil gelatinase-associated lipocalin is an early marker of acute kidney injury in adult critically ill patients: a prospective study. J Crit Care 2010;25:176:e1-6.
43. Niemann CU, Walia A, Waldman J, Davio M, Roberts JP, Hirose R, et al. Acute kidney injury during liver transplantation as determined by neutrophil gelatinase-associated lipocalin. Liver Transpl 2009;15:1852-60.
44. Portal AJ, McPhail MW, Bruce M, Coltart I, Slack A, Sherwood R, et al. Neutrophil gelatinase-associated lipocalin predicts acute kidney injury in patients undergoing liver transplantation. Liver Transpl 2010;16:1257-66.
45. Urine NGAL (REF 1P37). Product insert. Abbott Diagnostics Division, Longford, Ireland, 2009.
46. Haase-Fielitz A, Haase M, Bellomo R. Instability of urinary NGAL during long-term storage. Am J Kidney Dis 2009;53:564-5.
47. 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;5:2229-35.
48. Decavele AC, Dhondt L, De Buyzere ML, Delanghe J. Increased urinary neutrophil gelatinase associated lipocalin in urinary tract infections and leukocyturia. Clin Chem Lab Med 2011;49:999-1003.
49. Haase M, Bellomo R, Devarajan P, Schlattmann P, Haase-Fielitz A. 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;54:1012-24.
50. Koyner J, Vaidya VS, Bennett MR, Ma Q, Worcester E, Akhter SA, et al. Urinary biomarkers in the clinical prognosis and early detection of acute kidney injury. Clin J Am Soc Nephrol 2010:5:2154-65.
51. Wagener G, Gubitosa G, Wang S, Borregaard N, Kim M, Lee HT. Urinary neutrophil gelatinase-associated lipocalin and acute kidney injury after cardiac surgery. Am J Kidney Dis 2008;52:425-33.
52. Xin C, Yulong X, Yu C, Changchun C, Feng Z, Xinwei M. Urine neutrophil gelatinase-associated lipocalin and interleukin-18 predict acute kidney injury after cardiac surgery. Ren Fail 2008;30:904-13.
53. Bennett M, Dent CL, Ma Q, Dastrala S, Grenier F, Workman R, et al. Urine NGAL predicts severity of acute kidney injury after cardiac surgery: A prospective study. Clin J Am Soc Nephrol 2008;3:665-73.
54. Ling W, Zhaohui N, Ben H, Leyi G, Janping L, Huili D, et al. Urinary IL-18 and NGAL as early predictive biomarkers in contrast-induced nephropathy after coronary angiography. Nephron Clin Pract 2008;108:c176-81.
55. Nickolas TL, O'Rourke MJ, Yang J, Sise ME, Canetta PA, Barasch N, et al. Sensitivity and specificity of a single emergency department measurement of urinary neutrophil gelatinase-associated lipocalin for diagnosing acute kidney injury. Ann Intern Med 2008;148:810-19.
56. Zappitelli M, Washburn KM, Arikan AA, Loftis L, Ma Q, Devarajan P, et al. Urine NGAL is an early marker of acute kidney injury in critically ill children. Crit Care 2007;11:R84.
57. Makris K, Markou N, Evodia E, Dimiopoulou E, Drakopoulos I, Ntetsika K, et al. Urinary neutrophil gelatinase-associated lipocalin (NGAL) as an early marker of acute kidney injury in critically ill multiple trauma patients. Clin Chem Lab Med 2009;47:79-82.
58. Siew ED, Ware LB, Gebretsadik T, Shintani A, Moons KG, Wickersham N, et al. Urine neutrophil gelatinase-associated lipocalin moderately predicts acute kidney injury in critically ill adults. J Am Soc Nephrol 2009;20:1823-32.
59. Wagener G, Minhaz M, Mattis FA, Kim M, Emond JC, Lee HT. Urinary neutrophil gelatinase-associated lipocalin as a marker of acute kidney injury after orthotopic liver transplantation. Nephrol Dial Transplant 2011;26:1717-23.
60. Abraham BP, Frazier EA, Morrow WR, Blaszak RT, Devarajan P, Mitsnefes M, et al. Cystatin C and neutrophil gelatinase-associated lipocalin as markers of renal function in pediatric heart transplant recipients. Pediatr Transplant 2011;15:564-69.
61. Poniatowski B, Malyszko J, Bachorzewska-Gajewska H, Malyszk JS, Dobrzycki S. Serum neutrophil gelatinase-associated lipocalin as a marker of renal function in patients with chronic heart failure and coronary artery disease. Kidney Blood Press Res 2009;32:77-80.
62. Damman K, van Veldhuisen DJ, Navis G, Voors AA, Hillege HL. Urinary neutrophil gelatinase associated lipocalin (NGAL), a marker of tubular damage, is increased in patients with chronic heart failure. Eur J Heart Fail 2008;10:997-1000.
63. Bolignano D, Basile G, Parisi P, Coppolino G, Nicocia G, Buemi M. Increased plasma neutrophil gelatinase-associated lipocalin levels predict mortality in elderly patients with chronic heart failure. Rejuvenation Res 2009;12:7-14.
64. Damman K, Van Veldhuisen DJ, Navis G, Vaidya VS, Smilde TD, Westenbrink BD, et al. Tubular damage in chronic systolic heart failure is associated with reduced survival independent of glomerular filtration rate. Heart 2010;96:1297-302.
65. Damman K, Ng Kam Chuen MJ, MacFadyen RJ, Lip GY, Gaze D, Collinson PO, et al. Volume status and diuretic therapy in systolic heart failure and the detection of early abnormalities in renal and tubular function. J Am Coll Cardiol 2011;57:2233-41.
66. Shrestha K, Borowski AG, Troughton RW, Thomas JD, Klein AL, Tang WH. Renal dysfunction is a stronger determinant of systemic neutrophil gelatinase-associated lipocalin levels than myocardial dysfunction in systolic heart failure. J Card Fail 2011;17:472-8.
67. Damman K, Masson S, Hillege HL, Maggioni AP, Voors AA, Opasich C, et al. Clinical outcome of renal tubular damage in chronic heart failure. Eur Heart J 2011;32:2705-12.
68. Maisel AS, Mueller C, Fitzgerald R, Brikhan R, Hiestand BC, Iqbal N, et al. Prognostic utility of plasma neutrophil gelatinase-associated lipocalin in patients with acute heart failure: The NGAL evaluation along with B-type natriuretic peptide in acutely decompensated heart failure (GALLANT) trial. Eur J Heart Fail 2011;13:846-51.
69. Bagshaw SM, Bellomo R, Devarajan P, Johnson C, Carvellas CJ, Kutsiogiannis DJ, et al. Review article: acute kidney injury in critical illness. Can J Anaesth 2010;57:985-98.
70. Lattanzio MR, Kopyt NP. Acute kidney injury: new concepts in definition, diagnosis, pathophysiology, and treatment. J Am Osteopath Assoc 2009;109:13-19.
71. Supavekin S, Zhang W, Kucherlapati R, Kaskel FJ, Moore LC, Devarajan P. Differential gene expression following early renal ischemia-reperfusion. Kidney Int 2003;63:1714-24.
72. Devarajan P, Mishra J, Supavekin S, Patterson LT, Potter SS. Gene expression in early ischemic renal injury: clues towards pathogenesis, biomarker discovery, and novel therapeutics. Mol Genet Metab 2003;80:365-76.
73. Yuen PT, Jo S-K, Holly MK, Hu X, Star RA. Ischemic and nephrotoxic acute renal failure are distinguished by their broad transcriptomic responses. Physiol Genomics 2006;25:375-86.
74. Mishra J, Ma Q, Prada A, Mitsnefes M, Zahedi K, Yang J, et al. Identification of neutrophil gelatinase-associated lipocalin as a novel urinary biomarker for ischemic injury. J Am Soc Nephrol 2003;4:2534-43.
75. Devarajan P. Neutrophil gelatinase-associated lipocalin: a troponin-like biomarker for human acute kidney injury. Nephrology 2010;15:419-28.
76. Grigoryev DN, Liu M, Hassoun HT, Cheadle C, Barnes KC, Rabb H. The local and systemic inflammatory transcriptome after acute kidney injury. J Am Soc Nephrol 2008;19:547-58.
77. Mishra J, Ma Q, Kelly C, Mitsnefes M, Mori K, Barasch J, et al. Kidney NGAL is a novel early marker of acute injury following transplantation. Pediatr Nephrol 2006;21:856-63.
78. Parikh CR, Jani A, Mishra J, Ma Q, Kelly C, Barasch J, et al. Urine NGAL and IL-18 are predictive biomarkers for delayed graft function following kidney transplantation. Am J Transplant 2006;6:1639-45.
79. Kusaka M, Kuroyanagi Y, Mori T, Nagaoka K, Sasaki H, Maruyama T, et al. Serum neutrophil gelatinase-associated lipocalin as a predictor of organ recovery from delayed graft function after kidney transplantation from donors after cardiac death. Cell Transplant 2008;17:129-34.
80. Lebkowska U, Malyszko J, Lebkowska A, Koc-Zorawska E, Lebkowski W, Malyszko JS, et al. Neutrophil gelatinase-associated lipocalin and cystatin C could predict renal outcome in patients undergoing kidney allograft transplantation: a prospective study. Transplant Proc 2009;41:154-57.
81. Malyszko J, Malyszko JS, Mysliwiec M. Serum neutrophil gelatinase-associated lipocalin correlates with kidney function in renal allograft recipients. Clin Transplant 2009;23:681-86.
82. Malyszko J, Malyszko JS, Bachorzewska-Gajewska H, Poniatowski B, Dobrzycki S, Mysliwiec M. Neutrophil gelatinase-associated lipocalin is a new and sensitive marker of kidney function in chronic kidney disease patients and renal allograft recipients. Transplant Proc 2009;41:158-61.
83. Hall IE, Yarlagadda SG, Coca SG, Wang Z, Doshi M, Devarajan P, et al. IL-18 and urinary NGAL predict dialysis and graft recovery after kidney transplantation. J Am Soc Nephrol 2010;21:189-97.
84. Hollmen ME, Kyllonen LE, Inkinen KA, Lalla MT, Salmela KT. Urine neutrophil gelatinase-associated lipocalin is a marker of graft recovery after kidney transplantation. Kidney Int 2011;79:89-98.
85. Bataille A, Abbas S, Semoun O, Bourgeois E, Marie O, Bonnet F, et al. Plasma neutrophil gelatinase-associated lipocalin in kidney transplantation and early renal function prediction. Transplantation 2011;92:1024-30.
86. Nauta FL, Bakker SL, van Oeveren W, Navis G, van der Heyde JH, van Goor H, et al. Albuminuria, proteinuria, and novel urine biomarkers as predictors of long-term allograft outcomes in kidney transplant recipients. Am J Kidney Dis 2011;5:733-43.
87. Clerico A, Giannoni A, Prontera T, Giovannini S. High-sensitivity troponin: a new tool for pathophysiological investigation and clinical practice. Adv Clin Chem 2009;49:1-30.