Plasma and Urine Neutrophil Gelatinase-Associated Lipocalin (NGAL) as Early Predictor of Acute Kidney Injury in Septic Patients

Document Type : Original papers

Authors

1 Critical Care Medicine Department, Cairo University, Egypt

2 Anaesthesia and Surgical Intensive Care Department, Mansoura University, Egypt

3 Medical Biochemistry Department, Cairo University, Egypt

4 Emergency Medicine Department, Mansoura Univerisity hospital, Egypt

Abstract

Introduction: Sepsis is an important precipitant of acute kidney injury (AKI). Septic AKI may be characterized by a distinct pathophysiology. The lack of an early and effective biomarker results in a significant delay in initiating appropriate therapy.
Objective: to determine the role of plasma and urine neutrophil gelatinase-associated lipocalin (NGAL) as an early biomarker of acute kidney injury in septic patients.
Patients and methods: Prospective, observational study enrolled 40 critically ill patients with sepsis and septic shock. Plasma and urine NGAL were measured at enrollment and 12 h.
Results: Seventeen (42.5%) patients developed AKI. Patients with AKI, compared to those without, had significantly higher severity of illness, organ dysfunction, length of ICU stay, and more ICU mortality. AKI patients, compared to those without, had significantly higher baseline plasma NGAL (221.4 ± 104.7 vs. 129.5 ± 48 ng/ml, p = 0.003), and at 12 h (239.2 ± 122.9 vs. 128.9 ± 49.1 ng/ml, p = 0.002) and significantly higher urine NGAL at baseline (13.6 ± 5.5 vs. 7.8 ± 3 ng/ml, p = 0.001), and at 12 h (23.2 ± 6.5 vs. 15 ± 4.9 ng/ml, p = 0.0001). Baseline plasma NGAL ≥ 147 ng/ml had sensitivity of 82.4% and specificity of 73.9% for predicting AKI (AuROC 0.82), and urine NGAL at 12 h ≥ 19 ng/ml had sensitivity of 82.4% and specificity of 78.3% (AuROC 0.82). Conclusion: Plasma and urine NGAL are good predictors of AKI in critically ill septic patients

Keywords


  1. Nisula, S. Kaukonen, K.M. Vaara, et al. Incidence, risk factors and 90-day mortality of patients with acute kidney injury in Finnish intensive care units: the FINNAKI study Intensive Care Med 2013., 39: 420–428.
  2. Schrier RW, Wang W. Acute renal failure and sepsis. N Engl J Med 2004; 351: 159-169.
  3. Uchino S, Kellum JA, Bellomo R, et al. Beginning and Ending Supportive Therapy for the Kidney (BEST Kidney) Investigators. Acute renal failure in critically ill patients: a multinational, multicenter study. JAMA. 2005; 294(7): 813-8.
  4. Lopes JA, Jorge S, Resina C, et al. Acute kidney injury in patients with sepsis: a contemporary analysis. Int J Infect Dis. 2009;13(2): 176-81.
  5. Bagshaw SM, George C and Bellomo R; ANZICS Database Management Committee. Early acute kidney injury and sepsis: a multicentre evaluation. Crit Care. 2008;12(2): R47.
  6. Bagshaw SM, Langenberg C, Haase M, et al: Urinary biomarkers in septic acute kidney injury. Intensive Care Med 2007; 33: 1285-1296.
  7. Wan L, Bagshaw SM, Langenberg C, et al.Pathophysiology of septic acute kidney injury: what do we really know? Crit Care Med 2008; 36: 8198-8203.
  8. Bagshaw SM, Langenberg C, Wan L, et al: Asystematic review of urinary findings in experimental septic acute renal failure. Crit. Care Med 2007; 35: 1592-1598.
  9. Bellomo R, Kellum JA and Ronco C: Defining acute renal failure: physiological principles. Intensive Care Med 2004; 30: 33-37.
  10. Devarajan P: Emerging biomarkers of acute kidney injury. Contrib Nephrol 2007; 156: 203-212.
  11. Herget-Rosenthal S, Marggraf G, Hiising J, et al. Early detection of acute renal failure by serum cystatin C. Kidney Int 2004 ; 66: 1115-1122.
  12. Hirsch R, Dent C, Pfriem H, et al. NGAL is an early predictive biomarker of contrast-induced nephropamy in children. Pediatr Nephrol 2007; 22: 2089-2095.
  13. Mishra J, Mori K, Ma Q, et al. Neutrophil gelatinase-associated lipocain (NGAL): a novel urinary biomarker for ischemic injury. J Am Soc Nephrol 2003; 4: 2534-2543,
  14. Shaw AD, Chalfin DB, Kleintjens J. The economic impact and cost-effectiveness of urinary neutrophil gelatinase-associated lipocalin after cardiac surgery. Clin Ther. 2011; 33: 1713–1725.
  15. Mervyn Singer,  Clifford S. Deutschman,  Christopher Warren Seymour,   et al . Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). 2016;315(8):801-810.
  16. Kidney Disease: Improving Global Outcomes (KDIGO) Acute Kidney Injury Work Group. KDIGO clinical practice guideline for acute kidney injury. Kidney Int Suppl. 2012;1:1–138.
  17. Case J, Khan S, Khalid R, et al. Epidemiology of acute kidney injury in the intensive care unit. Crit Care Res Pract. 2013;2013: 479730.
  18. Uchino S, Kellum JA, Bellomo R, et al. Beginning and Ending Supportive Therapy for the Kidney (BEST Kidney) Investigators. Acute renal failure in critically ill patients: a multinational, multicenter study. JAMA. 2005; 294(7): 813-8.
  19. Piccinni P, Cruz DN, Gramaticopolo S,et al . Prospective multicenter study on epidemiology of acute kidney injury in the ICU: a critical care nephrology Italian collaborative effort (NEFROINT). Minerva Anestesiol. 2011;77(11): 1072-83
  20. Lopes JA, Jorge S, Resina C, et al. Acute kidney injury in patients with sepsis: a contemporary analysis. Int J Infect Dis. 2009;13(2): 176-81
  21. 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(11):810-9.
  22. Fjaertoft G, Foucard T, Xu S, Venge P: Human neutrophil lipocalin (HNL) as a diagnostic tool in children with acute infections: a study of the kinetics. Acta Paediatr 2005; 94(6):661-6.
  23. Suh SH, Kim CS, Choi JS, et al . Acute kidney injury in patients with sepsis and septic shock: risk factors and clinical outcomes. Yonsei Med J. 2013;54(4): 965-72.
  24. Feng JY, Liu KT, Abraham E,et al . Serum estradiol levels predict survival and acute kidney injury in patients with septic shock--a prospective study. PLoS One. 2014;9(6): e97967.
  25. Wang X, Jiang L, Wen Y,et al . Risk factors for mortality in patients with septic acute kidney injury in intensive care units in Beijing, China: a multicenter prospective observational study. Biomed Res Int2014; 172-620.
  26. Lopes, J.A. Jorge, S. Resina, et al. Acute renal failure in patients with sepsis Crit Care 2007;11: 411
  27. Bagshaw SM, Lapinsky S, Dial S,et al . Cooperative Antimicrobial Therapy of Septic Shock Database Research Group. Acute kidney injury in septic shock: clinical outcomes and impact of duration of hypotension prior to initiation of antimicrobial therapy. Intensive Care Med, 2009;35 : 871–881
  28. Bagshaw SM, Bennett M, Haase M,et al . Plasma and urine neutrophil gelatinase-associated lipocalin in septic versus non-septic acute kidney injury in critical illness. Intensive Care Med. 2010; 36: 452–461
  29. Plataki M, Kashani K, Cabello-Garza J,et al . Predictors of acute kidney injury in septic shock patients: an observational cohort study. Clin J Am Soc Nephrol. 2011; 6(7): 1744-51.
  30. Katagiri D, Doi K, Matsubara T,et al . New biomarker panel of plasma neutrophil gelatinase-associated lipocalin and endotoxin activity assay for detecting sepsis in acute kidney injury.J Crit Care. 2013;28(5): 564-70.
  31. Pickering JW, Endre ZH. The clinical utility of plasma neutrophil gelatinase-associated lipocalin in acute kidney injury. Blood Purif. 2013;35(4): 295-302.
  32. Camou F, Oger S, Paroissin C, et al . Plasma Neutrophil Gelatinase-Associated Lipocalin (NGAL) predicts acute kidney injury in septic shock at ICU admission. Ann Fr Anesth Reanim. 2013;32(3): 157-64.
  33. De Geus HR, Betjes MG, Schaick Rv, Groeneveld JA. Plasma NGAL similarly predicts acute kidney injury in sepsis and nonsepsis. Biomark Med. 2013;7(3): 415-21.
  34. Md Ralib A, Mat Nor MB, Pickering JW. Plasma Neutrophil Gelatinase Associated Lipocalin Diagnosed Acute Kidney Injury in Patie35. Cho E, Lee JH, Lim HJ, et al . Soluble CD25 is increased in patients with sepsis-induced acute kidney injury. Nephrology (Carlton). 2014;19(6): 318-24.
  35. Cho E, Lee JH, Lim HJ. Soluble CD25 is increased in patients with sepsis-induced acute kidney injury. Nephrology (Carlton). 2014;19(6): 318-24.
  36. Vanmassenhove J, Glorieux G, Lameire N, et al . Influence of severity of illness on neutrophil gelatinase-associated lipocalin performance as a marker of acute kidney injury: a prospective cohort study of patients with sepsis. BMC Nephrol. 2015;16: 18.
  37. Dai X, Zeng Z, Fu C, et al . 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 May 6;19: 223.
  38. Nga HS, Medeiros P, Menezes P, et al . Sepsis and AKI in Clinical Emergency Room Patients: The Role of Urinary NGAL. Biomed Res Int. 2015;2015: 413751.
  39. Zhang A, Cai Y, Wang PF, et al . Diagnosis and prognosis of neutrophil gelatinase-associated lipocalin for acute kidney injury with sepsis: a systematic review and meta-analysis. Crit Care. 2016 ;(16):20– 41.
  40. Kim S, Kim HJ, Ahn HS, et al . Is plasma neutrophil gelatinase-associated lipocalin a predictive biomarker for acute kidney injury in sepsis patients? A systematic review and meta-analysis.J Crit Care. 2016;33: 213-23.
  41. Mårtensson J, Bell M, Oldner A, et al . Neutrophil gelatinase-associated lipocalin in adult septic patients with and without acute kidney injury. Intensive Care Med. 2010;36(8): 1333-40.
  42. Aydoğdu M, Gürsel G, Sancak B, et al . The use of plasma and urine neutrophil gelatinase associated lipocalin (NGAL) and Cystatin C in early diagnosis of septic acute kidney injury in critically ill patients. Dis Markers. 2013; 34(4): 237-46.
  43. Nisula S, Yang R, Kaukonen KM, et al . The urine protein NGAL predicts renal replacement therapy, but not acute kidney injury or 90-day mortality in critically ill adult patients. Anesth Analg. 2014;119(1): 95-102.
  44. Törnblom, S., Nisula, S., Petäjä, L. et al.Urine NGAL as a biomarker for septic AKI: a critical appraisal of clinical utility—data from the observational FINNAKI study.  Intensive Care 10, 51 (2020).     
  45. Zhou, H., Cui, J., Lu, Y., Sun, J., Liu, J."Meta‑analysis of the diagnostic value of serum, plasma and urine neutrophil gelatinase‑associated lipocalin for the detection of acute kidney injury in patients with sepsis". Experimental and Therapeutic Medicine 21.4 (2021): 386.
  46. Yingqun Chen1, Jinbin Wu2, Zihan Yin1 , Xuwei Lin1 , Weixing Zhang1. THE VALUE OF NGAL, KIM-1 AND IL-18 FOR THE EARLY DIAGNOSIS OF SEPTIC SHOCK WITH ACUTE KIDNEY INJURY. Acta Medica Mediterranea, 2022, 38: 1777
  47. Bojic S, Kotur-Stevuljevic J, Kalezic N, et al . Diagnostic Value of Matrix Metalloproteinase-9 and Tissue Inhibitor of Matrix Metalloproteinase-1 in Sepsis-Associated Acute Kidney Injury. Tohoku J Exp Med. 2015; 237(2): 103-9.
  48. Tu Y, Wang H, Sun R, et al . Urinary netrin-1 and KIM-1 as early biomarkers for septic acute kidney injury. Ren Fail. 2014; 36(10): 1559-63.
  49. Cruz DN, de Cal M, Garzotto F, et al. Plasma neutrophil gelatinase-associated lipocalin is an early biomarker for acute kidney injury in an adult ICU population. Intensive Care Medicine. 2010;36(3): 444-451
  50. Perry TE, Muehlschlegel JD, Liu K-Y, et al . Plasma neutrophil gelatinase-associated lipocalin and acute postoperative kidney injury in adult cardiac surgical patients. Anesth. Analg. 2010; 110: 1541–1547.
  51. 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.
  52. 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.
  53. Koyner JL, Vaidya VS, Bennett MR, et al . Urinary biomarkers in the clinical prognosis and early detection of acute kidney injury. Clin J Am Soc Nephrol. 2010; 5: 2154–2165.
  54. Puthucheary ZA, Rawal J, McPhail M, et al. Acute skeletal muscle wasting in critical illness.JAMA 2013; 310: 1591–1600.
  55. Liu KD, Thompson BT, Ancukiewicz M, et al: Acute kidney injury in patients with acute lung injury: impact of fluid accumulation onclassification of acute kidney injury and associated outcomes. Crit Care Med 2011; 39 (12):2665-71.
  56. Haase M, Devarajan P, Haase-Fielitz A, et al. The outcome of neutrophil gelatinase-associatedlipocalin-positive subclinical acute kidney injury: a multicenter pooled analysis of prospective studies. J Am Coll Cardiol 2011; 57: 1752–1761.
  57. Nickolas TL, Schmidt-Ott KM, Canetta P, et al . Diagnostic and prognostic stratification in the emergency department using urinary biomarkers of nephron damage: a multicenter prospective cohort study. J. Am. Coll. Cardiol. 2012; 59: 246–255.
  58. Mitsnefes MM, Kathman TS, Mishra J, et al. Serum neutrophil gelatinase-associated lipocalin as a marker of renal function in children with chronic kidney disease. Pediatr Nephrol 2007; 22: 101–108.
  59. Bolignano D, Lacquaniti A, Coppolino G, et al: Neutrophil gelatinase-associated lipocalin and progression of chronic kidney disease. Clin J Am Soc Nephrol 2009; 4: 337–344.
  60. Kashani K, Al-Khafaji A, Ardiles T, et al. Discovery and validation of cell cycle arrest biomarkers in human acute kidney injury. Critical care. 2013; 17: R25.