American Journal of Kidney Diseases
Volume 54, Issue 6 , Pages 1012-1024 , December 2009

Accuracy of Neutrophil Gelatinase-Associated Lipocalin (NGAL) in Diagnosis and Prognosis in Acute Kidney Injury: A Systematic Review and Meta-analysis

  • Michael Haase, MD

      Affiliations

    • Department of Nephrology and Intensive Care Medicine, Charité University Medicine, Berlin, Germany
    • Corresponding Author InformationAddress correspondence to Michael Haase, MD, Department of Nephrology and Intensive Care Medicine, Charité-University Medicine Berlin, Campus Virchow-Klinikum, 13353 Berlin, Germany
    • ,
  • Rinaldo Bellomo, MD

      Affiliations

    • Department of Intensive Care, Austin Health, Melbourne, Australia
    • ,
  • Prasad Devarajan, MD

      Affiliations

    • Department of Pediatrics and Developmental Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH
    • ,
  • Peter Schlattmann, MD, MSc

      Affiliations

    • Department of Biometry and Clinical Epidemiology, Charité University Medicine, Campus Mitte, Berlin, Germany
    • ,
  • Anja Haase-Fielitz, PharmD

      Affiliations

    • Department of Nephrology and Intensive Care Medicine, Charité University Medicine, Berlin, Germany
    • ,
  • NGAL Meta-analysis Investigator Group

Received 15 April 2009 ,Accepted 27 July 2009.

References 

  1. Stafford-Smith M, Podgoreanu M, Swaminathan M, et al. Association of genetic polymorphisms with risk of renal injury after coronary bypass graft surgery. Am J Kidney Dis. 2005;45:519–530
  2. Morgera S, Kraft AK, Siebert G, Luft FC, Neumayer HH. Long-term outcomes in acute renal failure patients treated with continuous renal replacement therapies. Am J Kidney Dis. 2002;40:275–279
  3. Chertow GM, Burdick E, Honour M, et al. Acute kidney injury, mortality, length of stay, and costs in hospitalized patients. J Am Soc Nephrol. 2005;16:3365–3370
  4. Bellomo R, Chapman M, Finfer S, Hickling K, Myburgh J. Low-dose dopamine in patients with early renal dysfunction: a placebo-controlled randomised trial (Australian and New Zealand Intensive Care Society Clinical Trials Group). Lancet. 2000;356:2139–2143
  5. Lauschke A, Teichgräber UK, Frei U, et al. ‘Low-dose' dopamine worsens renal perfusion in patients with acute renal failure. Kidney Int. 2006;69:1669–1674
  6. Allgren RL, Marbury TC, Rahman SN, et al. Anaritide in acute tubular necrosis. N Engl J Med. 1997;336:828–834
  7. Herget-Rosenthal S, Marggraf G, Hüsing J, et al. Early detection of acute renal failure by serum cystatin C. Kidney Int. 2004;66:1115–1122
  8. Kellum JA, Mehta RL, Levin A, et al. Development of a clinical research agenda for acute kidney injury using an international, interdisciplinary, three-step modified Delphi process. Clin J Am Soc Nephrol. 2008;3:887–894
  9. Kellum JA, Levin N, Bouman C, Lameire N. Developing a consensus classification system for acute renal failure. Curr Opin Crit Care. 2002;8:509–514
  10. Mishra J, Ma Q, Prada A, et al. Identification of neutrophil gelatinase-associated lipocalin as a novel early urinary biomarker for ischemic renal injury. J Am Soc Nephrol. 2003;14:2534–2543
  11. Supavekin S, Zhang W, Kucherlapati R, Kaskel FJ, Moore LC, Devarajan P. Differential gene expression following early renal ischemia/reperfusion. Kidney Int. 2003;63:1714–1724
  12. Mori K, Lee HT, Rapoport D, et al. Endocytic delivery of lipocalin-siderophore-iron complex rescues the kidney from ischemia-reperfusion injury. J Clin Invest. 2005;115:610–621
  13. 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;365:1231–1238
  14. Nickolas TL, O'Rourke MJ, Yang J, 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;148:810–819
  15. Wagener G, Jan M, Kim M, et al. Association between increases in urinary neutrophil gelatinase-associated lipocalin and acute renal dysfunction after adult cardiac surgery. Anesthesiology. 2006;105:485–491
  16. Bennett M, Dent CL, Ma Q, et al. Urine NGAL predicts severity of acute kidney injury after cardiac surgery: a prospective study. Clin J Am Soc Nephrol. 2008;3:665–673
  17. Haase-Fielitz A, Bellomo R, Devarajan P, et al. Novel and conventional serum biomarkers predicting acute kidney injury in adult cardiac surgery—a prospective cohort study. Crit Care Med. 2009;37:553–560
  18. 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:R84
  19. Wheeler DS, Devarajan P, Ma Q, 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;36:1297–1303
  20. Ling W, Zhaohui N, Ben H, et al. Urinary IL-18 and NGAL as early predictive biomarkers in contrast-induced nephropathy after coronary angiography. Nephron Clin Pract. 2008;108:c176–c181
  21. 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;26:287–292
  22. 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;74:1059–1069
  23. Hirsch R, Dent C, Pfriem H, et al. NGAL is an early predictive biomarker of contrast-induced nephropathy in children. Pediatr Nephrol. 2007;22:2089–2095
  24. Tuladhar SM, Püntmann VO, Soni M, et al. Rapid detection of acute kidney injury by plasma and urinary neutrophil gelatinase-associated lipocalin after cardiopulmonary bypass. J Cardiovasc Pharmacol. 2009;53:261–266
  25. Dent CL, Ma Q, Dastrala S, 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
  26. Wagener G, Gubitosa G, Wang S, Borregaard N, Kim M, Lee HT. Urinary neutrophil gelatinase-associated lipocalin and acute kidney injury after cardiac surgery. [erratum in Am J Kidney Dis. 2008;52:810] Am J Kidney Dis. 2008;52:425–433
  27. Lima ED, Miranda R, Machado M, et al. Role of neutrophil gelatinase-associated lipocalin (NGAL) in the early diagnosis of acute kidney injury after cardiopulmonary bypass. [abstract] J Am Soc Nephrol. 2008;19:569A
  28. 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;30:904–913
  29. Cruz D, de Cal M, Garzotto F, et al. Neutrophil gelatinase-associated lipocalin is an early biomarker for acute kidney injury in an adult ICU population. [abstract] J Am Soc Nephrol. 2008;19:565A–566A
  30. Makris K, Demponeras C, Zoubouloglou F, et al. The role of urinary NGAL to urinary creatinine ratio in the early detection of contrast agent induced acute kidney injury after coronary artery angiography. Poster presented at the American Association for Clinical Chemistry 2009; July 19-23, 2009; Chicago, IL.
  31. Makris K, Markou N, Evodia E, 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
  32. Constantin JM, Futier E, Sebastien P, 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. 2009;in press
  33. Stroup DF, Berlin JA, Morton SC, et al. Meta-analysis of Observational Studies in Epidemiology: a proposal for reporting (Meta-analysis of Observational Studies in Epidemiology (MOOSE) Group). JAMA. 2000;283:2008–2012
  34. Levey AS, Coresh J, Greene T, et al. Expressing the Modification of Diet in Renal Disease Study equation for estimating glomerular filtration rate with standardized serum creatinine values. Clin Chem. 2007;53:766–772
  35. Bellomo R, Ronco C, Kellum JA, et al. Acute renal failure—definition, outcome measures, animal models, fluid therapy and information technology needs: 2nd International Consensus Conference of the ADQI Group. Crit Care. 2004;8:R204–R212
  36. Fung JW, Szeto CC, Chan WW, et al. Effect of N-acetylcysteine for prevention of contrast nephropathy in patients with moderate to severe renal insufficiency: a randomized trial. Am J Kidney Dis. 2004;43:801–808
  37. Deeks JJ, Macaskill P, Irwig L. The performance of tests of publication bias and other sample size effects in systematic reviews of diagnostic test accuracy was assessed. J Clin Epidemiol. 2005;58:882–893
  38. Harbord RM, Deeks JJ, Egger M, et al. A unification of models for meta-analysis of diagnostic accuracy studies. Biostatistics. 2007;8:239–251
  39. Farr BM, Shapiro DE. Diagnostic tests: distinguishing good tests from bad and even ugly ones. Infect Control Hosp Epidemiol. 2000;21:278–284
  40. Zweig MH, Campbell G. Receiver-operating characteristic (ROC) plots: a fundamental evaluation tool in clinical medicine. Clin Chem. 1993;39:561–577
  41. Dharnidharka VR, Kwon C, Stevens G. Serum cystatin C is superior to serum creatinine as a marker of kidney function: a meta-analysis. Am J Kidney Dis. 2002;40:221–226
  42. Swets JA. Measuring the accuracy of diagnostic systems. Science. 1988;240:1285–1293
  43. Higgins JP, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta-analyses. BMJ. 2003;327:557–560
  44. Haase-Fielitz A, Bellomo R, Devarajan P, et al. The predictive performance of plasma neutrophil gelatinase-associated lipocalin (NGAL) increases with grade of acute kidney injury. Nephrol Dial Transplant. 2009 May 27;[Epub ahead of print]
  45. Portilla D, Dent C, Sugaya T. Liver fatty acid-binding protein as a biomarker of acute kidney injury after cardiac surgery. Kidney Int. 2008;73:465–472
  46. Ichimura T, Hung CC, Yang SA, Stevens JL, Bonventre JV. Kidney injury molecule-1: a tissue and urinary biomarker for nephrotoxicant-induced renal injury. Am J Physiol Renal Physiol. 2004;286:F552–F563
  47. Parikh CR, Jani A, Melnikov VY, Faubel S, Edelstein CL. Urinary interleukin-18 is a marker of human acute tubular necrosis. Am J Kidney Dis. 2004;43:405–414
  48. Mehta RL, Kellum JA, Shah SV, et al. Acute Kidney Injury Network: report of an initiative to improve outcomes in acute kidney injury. Crit Care. 2007;11(2):R31
  49. Waikar S, Bonventre J. Transient changes in creatinine-normalized urine biomarker concentrations in acute kidney injury: caveats for interpretation. [abstract] J Am Soc Nephrol. 2008;19:572A
  50. Haase-Fielitz A, Haase M, Bellomo R. Instability of urinary NGAL during long-term storage. Am J Kidney Dis. 2009;53:564–565
  51. Lassnigg A, Schmid ER, Hiesmayr M, et al. Impact of minimal increases in serum creatinine on outcome in patients after cardiothoracic surgery: do we have to revise current definitions of acute renal failure?. Crit Care Med. 2008;36:1129–1137
  52. Tanasijevic MJ, Cannon CP, Antman EM, et al. Myoglobin, creatine-kinase-MB and cardiac troponin-I 60-minute ratios predict infarct-related artery patency after thrombolysis for acute myocardial infarction: results from the Thrombolysis in Myocardial Infarction study (TIMI) 10B. J Am Coll Cardiol. 1999;34:739–747
  53. Cruz DN, Soni S, Ronco C. NGAL and cardiac surgery-associated acute kidney injury. Am J Kidney Dis. 2009;53:565–566

 Originally published online as doi:10.1053/j.ajkd.2009.07.020 on October 22, 2009.

 Members of the NGAL Meta-analysis Investigator Group are listed at the end of this article.

PII: S0272-6386(09)01075-0

doi: 10.1053/j.ajkd.2009.07.020

American Journal of Kidney Diseases
Volume 54, Issue 6 , Pages 1012-1024 , December 2009

Article Tools

* Image Usage & Resolution