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Published in: Intensive Care Medicine 8/2010

01-08-2010 | Original

Neutrophil gelatinase-associated lipocalin in adult septic patients with and without acute kidney injury

Authors: Johan Mårtensson, Max Bell, Anders Oldner, Shengyuan Xu, Per Venge, Claes-Roland Martling

Published in: Intensive Care Medicine | Issue 8/2010

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Abstract

Purpose

To study the impact of inflammation/sepsis on the concentrations of neutrophil gelatinase-associated lipocalin (NGAL) in plasma and urine in adult intensive care unit (ICU) patients and to estimate the predictive properties of NGAL in plasma and urine for early detection of acute kidney injury (AKI) in patients with septic shock.

Methods

Sixty-five patients admitted to the general ICU at the Karolinska University Hospital Solna, Sweden, with normal plasma creatinine were assessed for eligibility. Twenty-seven patients with systemic inflammatory response syndrome (SIRS), severe sepsis, or septic shock without AKI and 18 patients with septic shock and concomitant AKI were included in the final analysis. Plasma and urine were analyzed twice daily for plasma NGAL (pNGAL), C-reactive protein (CRP), procalcitonin, myeloperoxidase, plasma cystatin C, plasma creatinine, urine NGAL (uNGAL), urine cystatin C, and urine α1-microglobulin.

Results

Of the 45 patients, 40 had elevated peak levels of pNGAL. Peak levels of pNGAL were not significantly different between septic shock patients with and without AKI. Peak levels of uNGAL were below the upper reference limit in all but four patients without AKI. uNGAL was a good predictor (area under ROC 0.86) whereas pNGAL was a poor predictor (area under ROC 0.67) for AKI within the next 12 h in patients with septic shock.

Conclusions

pNGAL is raised in patients with SIRS, severe sepsis, and septic shock and should be used with caution as a marker of AKI in ICU patients with septic shock. uNGAL is more useful in predicting AKI as the levels are not elevated in septic patients without AKI.
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Literature
1.
go back to reference Mishra J, Dent C, Tarabishi R, Mitsnefes MM, Ma Q, Kelly C, Ruff SM, Zahedi K, Shao M, Bean J, Mori K, Barasch J, Devarajan P (2005) Neutrophil gelatinase-associated lipocalin (NGAL) as a biomarker for acute renal injury after cardiac surgery. Lancet 365:1231–1238CrossRefPubMed Mishra J, Dent C, Tarabishi R, Mitsnefes MM, Ma Q, Kelly C, Ruff SM, Zahedi K, Shao M, Bean J, Mori K, Barasch J, Devarajan P (2005) Neutrophil gelatinase-associated lipocalin (NGAL) as a biomarker for acute renal injury after cardiac surgery. Lancet 365:1231–1238CrossRefPubMed
2.
go back to reference Wagener G, Jan M, Kim M, Mori K, Barasch JM, Sladen RN, Lee HT (2006) Association between increases in urinary neutrophil gelatinase-associated lipocalin and acute renal dysfunction after adult cardiac surgery. Anesthesiology 105:485–491CrossRefPubMed Wagener G, Jan M, Kim M, Mori K, Barasch JM, Sladen RN, Lee HT (2006) Association between increases in urinary neutrophil gelatinase-associated lipocalin and acute renal dysfunction after adult cardiac surgery. Anesthesiology 105:485–491CrossRefPubMed
3.
go back to reference Hirsch R, Dent C, Pfriem H, Allen J, Beekman RH 3rd, Ma Q, Dastrala S, Bennett M, Mitsnefes M, Devarajan P (2007) NGAL is an early predictive biomarker of contrast-induced nephropathy in children. Pediatr Nephrol 22:2089–2095CrossRefPubMed Hirsch R, Dent C, Pfriem H, Allen J, Beekman RH 3rd, Ma Q, Dastrala S, Bennett M, Mitsnefes M, Devarajan P (2007) NGAL is an early predictive biomarker of contrast-induced nephropathy in children. Pediatr Nephrol 22:2089–2095CrossRefPubMed
4.
go back to reference Bachorzewska-Gajewska H, Malyszko J, Sitniewska E, Malyszko JS, Pawlak K, Mysliwiec M, Lawnicki S, Szmitkowski M, Dobrzycki S (2007) Could neutrophil-gelatinase-associated lipocalin and cystatin C predict the development of contrast-induced nephropathy after percutaneous coronary interventions in patients with stable angina and normal serum creatinine values? Kidney Blood Press Res 30:408–415CrossRefPubMed Bachorzewska-Gajewska H, Malyszko J, Sitniewska E, Malyszko JS, Pawlak K, Mysliwiec M, Lawnicki S, Szmitkowski M, Dobrzycki S (2007) Could neutrophil-gelatinase-associated lipocalin and cystatin C predict the development of contrast-induced nephropathy after percutaneous coronary interventions in patients with stable angina and normal serum creatinine values? Kidney Blood Press Res 30:408–415CrossRefPubMed
5.
go back to reference Xu SY, Pauksen K, Venge P (1995) Serum measurements of human neutrophil lipocalin (HNL) discriminate between acute bacterial and viral infections. Scand J Clin Lab Invest 55:125–131CrossRefPubMed Xu SY, Pauksen K, Venge P (1995) Serum measurements of human neutrophil lipocalin (HNL) discriminate between acute bacterial and viral infections. Scand J Clin Lab Invest 55:125–131CrossRefPubMed
6.
go back to reference Fjaertoft G, Foucard T, Xu S, Venge P (2005) Human neutrophil lipocalin (HNL) as a diagnostic tool in children with acute infections: a study of the kinetics. Acta Paediatr 94:661–666CrossRefPubMed Fjaertoft G, Foucard T, Xu S, Venge P (2005) Human neutrophil lipocalin (HNL) as a diagnostic tool in children with acute infections: a study of the kinetics. Acta Paediatr 94:661–666CrossRefPubMed
7.
go back to reference Mori K, Lee HT, Rapoport D, Drexler IR, Foster K, Yang J, Schmidt-Ott KM, Chen X, Li JY, Weiss S, Mishra J, Cheema FH, Markowitz G, Suganami T, Sawai K, Mukoyama M, Kunis C, D’Agati V, Devarajan P, Barasch J (2005) Endocytic delivery of lipocalin-siderophore-iron complex rescues the kidney from ischemia-reperfusion injury. J Clin Invest 115:610–621PubMed Mori K, Lee HT, Rapoport D, Drexler IR, Foster K, Yang J, Schmidt-Ott KM, Chen X, Li JY, Weiss S, Mishra J, Cheema FH, Markowitz G, Suganami T, Sawai K, Mukoyama M, Kunis C, D’Agati V, Devarajan P, Barasch J (2005) Endocytic delivery of lipocalin-siderophore-iron complex rescues the kidney from ischemia-reperfusion injury. J Clin Invest 115:610–621PubMed
8.
go back to reference Uchino S, Kellum JA, Bellomo R, Doig GS, Morimatsu H, Morgera S, Schetz M, Tan I, Bouman C, Macedo E, Gibney N, Tolwani A, Ronco C (2005) Acute renal failure in critically ill patients: a multinational, multicenter study. JAMA 294:813–818CrossRefPubMed Uchino S, Kellum JA, Bellomo R, Doig GS, Morimatsu H, Morgera S, Schetz M, Tan I, Bouman C, Macedo E, Gibney N, Tolwani A, Ronco C (2005) Acute renal failure in critically ill patients: a multinational, multicenter study. JAMA 294:813–818CrossRefPubMed
9.
go back to reference Bagshaw SM, Uchino S, Bellomo R, Morimatsu H, Morgera S, Schetz M, Tan I, Bouman C, Macedo E, Gibney N, Tolwani A, Oudemans-van Straaten HM, Ronco C, Kellum JA (2007) Septic acute kidney injury in critically ill patients: clinical characteristics and outcomes. Clin J Am Soc Nephrol 2:431–439CrossRefPubMed Bagshaw SM, Uchino S, Bellomo R, Morimatsu H, Morgera S, Schetz M, Tan I, Bouman C, Macedo E, Gibney N, Tolwani A, Oudemans-van Straaten HM, Ronco C, Kellum JA (2007) Septic acute kidney injury in critically ill patients: clinical characteristics and outcomes. Clin J Am Soc Nephrol 2:431–439CrossRefPubMed
10.
go back to reference Cruz DN, de Cal M, Garzotto F, Perazella MA, Lentini P, Corradi V, Piccinni P, Ronco C (2010) Plasma neutrophil gelatinase-associated lipocalin is an early biomarker for acute kidney injury in an adult ICU population. Intensive Care Med 36:444–451CrossRefPubMed Cruz DN, de Cal M, Garzotto F, Perazella MA, Lentini P, Corradi V, Piccinni P, Ronco C (2010) Plasma neutrophil gelatinase-associated lipocalin is an early biomarker for acute kidney injury in an adult ICU population. Intensive Care Med 36:444–451CrossRefPubMed
11.
go back to reference Wheeler DS, Devarajan P, Ma Q, Harmon K, Monaco M, Cvijanovich N, Wong HR (2008) Serum neutrophil gelatinase-associated lipocalin (NGAL) as a marker of acute kidney injury in critically ill children with septic shock. Crit Care Med 36:1297–1303CrossRefPubMed Wheeler DS, Devarajan P, Ma Q, Harmon K, Monaco M, Cvijanovich N, Wong HR (2008) Serum neutrophil gelatinase-associated lipocalin (NGAL) as a marker of acute kidney injury in critically ill children with septic shock. Crit Care Med 36:1297–1303CrossRefPubMed
12.
go back to reference Zappitelli M, Washburn KK, Arikan AA, Loftis L, Ma Q, Devarajan P, Parikh CR, Goldstein SL (2007) Urine neutrophil gelatinase-associated lipocalin is an early marker of acute kidney injury in critically ill children: a prospective cohort study. Crit Care 11:R84CrossRefPubMed Zappitelli M, Washburn KK, Arikan AA, Loftis L, Ma Q, Devarajan P, Parikh CR, Goldstein SL (2007) Urine neutrophil gelatinase-associated lipocalin is an early marker of acute kidney injury in critically ill children: a prospective cohort study. Crit Care 11:R84CrossRefPubMed
13.
go back to reference Bagshaw SM, Bennett M, Haase M, Haase-Fielitz A, Egi M, Morimatsu H, D’Amico G, Goldsmith D, Devarajan P, Bellomo R (2010) Plasma and urine neutrophil gelatinase-associated lipocalin in septic versus non-septic acute kidney injury in critical illness. Intensive Care Med 36:452–461CrossRefPubMed Bagshaw SM, Bennett M, Haase M, Haase-Fielitz A, Egi M, Morimatsu H, D’Amico G, Goldsmith D, Devarajan P, Bellomo R (2010) Plasma and urine neutrophil gelatinase-associated lipocalin in septic versus non-septic acute kidney injury in critical illness. Intensive Care Med 36:452–461CrossRefPubMed
14.
go back to reference Bellomo R, Ronco C, Kellum JA, Mehta RL, Palevsky P (2004) 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 8:R204–R212CrossRefPubMed Bellomo R, Ronco C, Kellum JA, Mehta RL, Palevsky P (2004) 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 8:R204–R212CrossRefPubMed
15.
go back to reference Mehta RL, Kellum JA, Shah SV, Molitoris BA, Ronco C, Warnock DG, Levin A (2007) Acute kidney injury network: report of an initiative to improve outcomes in acute kidney injury. Crit Care 11:R31CrossRefPubMed Mehta RL, Kellum JA, Shah SV, Molitoris BA, Ronco C, Warnock DG, Levin A (2007) Acute kidney injury network: report of an initiative to improve outcomes in acute kidney injury. Crit Care 11:R31CrossRefPubMed
16.
go back to reference Kellum JA, Bellomo R, Ronco C (2008) Definition and classification of acute kidney injury. Nephron Clin Pract 109:c182–c187CrossRefPubMed Kellum JA, Bellomo R, Ronco C (2008) Definition and classification of acute kidney injury. Nephron Clin Pract 109:c182–c187CrossRefPubMed
17.
go back to reference Bone RC, Balk RA, Cerra FB, Dellinger RP, Fein AM, Knaus WA, Schein RM, Sibbald WJ (1992) Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis The ACCP/SCCM consensus conference committee. American College of Chest Physicians/Society of Critical Care Medicine. Chest 101:1644–1655CrossRefPubMed Bone RC, Balk RA, Cerra FB, Dellinger RP, Fein AM, Knaus WA, Schein RM, Sibbald WJ (1992) Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis The ACCP/SCCM consensus conference committee. American College of Chest Physicians/Society of Critical Care Medicine. Chest 101:1644–1655CrossRefPubMed
18.
go back to reference Bernard GR, Vincent JL, Laterre PF, LaRosa SP, Dhainaut JF, Lopez-Rodriguez A, Steingrub JS, Garber GE, Helterbrand JD, Ely EW, Fisher CJ Jr (2001) Efficacy and safety of recombinant human activated protein C for severe sepsis. N Engl J Med 344:699–709CrossRefPubMed Bernard GR, Vincent JL, Laterre PF, LaRosa SP, Dhainaut JF, Lopez-Rodriguez A, Steingrub JS, Garber GE, Helterbrand JD, Ely EW, Fisher CJ Jr (2001) Efficacy and safety of recombinant human activated protein C for severe sepsis. N Engl J Med 344:699–709CrossRefPubMed
19.
go back to reference Xu SY, Petersson CG, Carlson M, Venge P (1994) The development of an assay for human neutrophil lipocalin (HNL)—to be used as a specific marker of neutrophil activity in vivo and vitro. J Immunol Methods 171:245–252CrossRefPubMed Xu SY, Petersson CG, Carlson M, Venge P (1994) The development of an assay for human neutrophil lipocalin (HNL)—to be used as a specific marker of neutrophil activity in vivo and vitro. J Immunol Methods 171:245–252CrossRefPubMed
20.
go back to reference Cai L, Borowiec J, Xu S, Han W, Venge P (2009) 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 403:121–125CrossRefPubMed Cai L, Borowiec J, Xu S, Han W, Venge P (2009) 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 403:121–125CrossRefPubMed
21.
go back to reference Nickolas TL, O’Rourke MJ, Yang J, Sise ME, Canetta PA, Barasch N, Buchen C, Khan F, Mori K, Giglio J, Devarajan P, Barasch J (2008) Sensitivity and specificity of a single emergency department measurement of urinary neutrophil gelatinase-associated lipocalin for diagnosing acute kidney injury. Ann Intern Med 148:810–819PubMed Nickolas TL, O’Rourke MJ, Yang J, Sise ME, Canetta PA, Barasch N, Buchen C, Khan F, Mori K, Giglio J, Devarajan P, Barasch J (2008) Sensitivity and specificity of a single emergency department measurement of urinary neutrophil gelatinase-associated lipocalin for diagnosing acute kidney injury. Ann Intern Med 148:810–819PubMed
22.
go back to reference Makris K, Markou N, Evodia E, Dimopoulou E, Drakopoulos I, Ntetsika K, Rizos D, Baltopoulos G, Haliassos A (2009) Urinary neutrophil gelatinase-associated lipocalin (NGAL) as an early marker of acute kidney injury in critically ill multiple trauma patients. Clin Chem Lab Med 47:79–82CrossRefPubMed Makris K, Markou N, Evodia E, Dimopoulou E, Drakopoulos I, Ntetsika K, Rizos D, Baltopoulos G, Haliassos A (2009) Urinary neutrophil gelatinase-associated lipocalin (NGAL) as an early marker of acute kidney injury in critically ill multiple trauma patients. Clin Chem Lab Med 47:79–82CrossRefPubMed
23.
go back to reference Xu SY, Carlson M, Engstrom A, Garcia R, Peterson CG, Venge P (1994) Purification and characterization of a human neutrophil lipocalin (HNL) from the secondary granules of human neutrophils. Scand J Clin Lab Invest 54:365–376CrossRefPubMed Xu SY, Carlson M, Engstrom A, Garcia R, Peterson CG, Venge P (1994) Purification and characterization of a human neutrophil lipocalin (HNL) from the secondary granules of human neutrophils. Scand J Clin Lab Invest 54:365–376CrossRefPubMed
24.
go back to reference Brunkhorst FM, Wegscheider K, Forycki ZF, Brunkhorst R (2000) Procalcitonin for early diagnosis and differentiation of SIRS, sepsis, severe sepsis, and septic shock. Intensive Care Med 26(Suppl 2):S148–S152PubMed Brunkhorst FM, Wegscheider K, Forycki ZF, Brunkhorst R (2000) Procalcitonin for early diagnosis and differentiation of SIRS, sepsis, severe sepsis, and septic shock. Intensive Care Med 26(Suppl 2):S148–S152PubMed
25.
go back to reference Luzzani A, Polati E, Dorizzi R, Rungatscher A, Pavan R, Merlini A (2003) Comparison of procalcitonin and C-reactive protein as markers of sepsis. Crit Care Med 31:1737–1741CrossRefPubMed Luzzani A, Polati E, Dorizzi R, Rungatscher A, Pavan R, Merlini A (2003) Comparison of procalcitonin and C-reactive protein as markers of sepsis. Crit Care Med 31:1737–1741CrossRefPubMed
26.
go back to reference Dent CL, Ma Q, Dastrala S, Bennett M, Mitsnefes MM, Barasch J, Devarajan P (2007) Plasma neutrophil gelatinase-associated lipocalin predicts acute kidney injury, morbidity and mortality after pediatric cardiac surgery: a prospective uncontrolled cohort study. Crit Care 11:R127CrossRefPubMed Dent CL, Ma Q, Dastrala S, Bennett M, Mitsnefes MM, Barasch J, Devarajan P (2007) Plasma neutrophil gelatinase-associated lipocalin predicts acute kidney injury, morbidity and mortality after pediatric cardiac surgery: a prospective uncontrolled cohort study. Crit Care 11:R127CrossRefPubMed
27.
go back to reference Tuladhar SM, Puntmann VO, Soni M, Punjabi PP, Bogle RG (2009) Rapid detection of acute kidney injury by plasma and urinary neutrophil gelatinase-associated lipocalin after cardiopulmonary bypass. J Cardiovasc Pharmacol 53:261–266CrossRefPubMed Tuladhar SM, Puntmann VO, Soni M, Punjabi PP, Bogle RG (2009) Rapid detection of acute kidney injury by plasma and urinary neutrophil gelatinase-associated lipocalin after cardiopulmonary bypass. J Cardiovasc Pharmacol 53:261–266CrossRefPubMed
28.
go back to reference Bell M, Granath F, Martensson J, Lofberg E, Ekbom A, Martling CR (2009) Cystatin C is correlated with mortality in patients with and without acute kidney injury. Nephrol Dial Transplant 24:3096–3102CrossRefPubMed Bell M, Granath F, Martensson J, Lofberg E, Ekbom A, Martling CR (2009) Cystatin C is correlated with mortality in patients with and without acute kidney injury. Nephrol Dial Transplant 24:3096–3102CrossRefPubMed
29.
go back to reference Risch L, Herklotz R, Blumberg A, Huber AR (2001) Effects of glucocorticoid immunosuppression on serum cystatin C concentrations in renal transplant patients. Clin Chem 47:2055–2059PubMed Risch L, Herklotz R, Blumberg A, Huber AR (2001) Effects of glucocorticoid immunosuppression on serum cystatin C concentrations in renal transplant patients. Clin Chem 47:2055–2059PubMed
30.
go back to reference Poge U, Gerhardt T, Bokenkamp A, Stoffel-Wagner B, Klehr HU, Sauerbruch T, Woitas RP (2004) Time course of low molecular weight proteins in the early kidney transplantation period—influence of corticosteroids. Nephrol Dial Transplant 19:2858–2863CrossRefPubMed Poge U, Gerhardt T, Bokenkamp A, Stoffel-Wagner B, Klehr HU, Sauerbruch T, Woitas RP (2004) Time course of low molecular weight proteins in the early kidney transplantation period—influence of corticosteroids. Nephrol Dial Transplant 19:2858–2863CrossRefPubMed
31.
go back to reference Bokenkamp A, Laarman CA, Braam KI, van Wijk JA, Kors WA, Kool M, de Valk J, Bouman AA, Spreeuwenberg MD, Stoffel-Wagner B (2007) Effect of corticosteroid therapy on low-molecular weight protein markers of kidney function. Clin Chem 53:2219–2221CrossRefPubMed Bokenkamp A, Laarman CA, Braam KI, van Wijk JA, Kors WA, Kool M, de Valk J, Bouman AA, Spreeuwenberg MD, Stoffel-Wagner B (2007) Effect of corticosteroid therapy on low-molecular weight protein markers of kidney function. Clin Chem 53:2219–2221CrossRefPubMed
32.
go back to reference Strevens H, Wide-Swensson D, Grubb A, Hansen A, Horn T, Ingemarsson I, Larsen S, Nyengaard JR, Torffvit O, Willner J, Olsen S (2003) Serum cystatin C reflects glomerular endotheliosis in normal, hypertensive and pre-eclamptic pregnancies. BJOG 110:825–830CrossRefPubMed Strevens H, Wide-Swensson D, Grubb A, Hansen A, Horn T, Ingemarsson I, Larsen S, Nyengaard JR, Torffvit O, Willner J, Olsen S (2003) Serum cystatin C reflects glomerular endotheliosis in normal, hypertensive and pre-eclamptic pregnancies. BJOG 110:825–830CrossRefPubMed
33.
go back to reference Joannidis M, Metnitz B, Bauer P, Schusterschitz N, Moreno R, Druml W, Metnitz PG (2009) Acute kidney injury in critically ill patients classified by AKIN versus RIFLE using the SAPS 3 database. Intensive Care Med 35:1692–1702CrossRefPubMed Joannidis M, Metnitz B, Bauer P, Schusterschitz N, Moreno R, Druml W, Metnitz PG (2009) Acute kidney injury in critically ill patients classified by AKIN versus RIFLE using the SAPS 3 database. Intensive Care Med 35:1692–1702CrossRefPubMed
34.
go back to reference Axelsson L, Bergenfeldt M, Ohlsson K (1995) Studies of the release and turnover of a human neutrophil lipocalin. Scand J Clin Lab Invest 55:577–588CrossRefPubMed Axelsson L, Bergenfeldt M, Ohlsson K (1995) Studies of the release and turnover of a human neutrophil lipocalin. Scand J Clin Lab Invest 55:577–588CrossRefPubMed
Metadata
Title
Neutrophil gelatinase-associated lipocalin in adult septic patients with and without acute kidney injury
Authors
Johan Mårtensson
Max Bell
Anders Oldner
Shengyuan Xu
Per Venge
Claes-Roland Martling
Publication date
01-08-2010
Publisher
Springer-Verlag
Published in
Intensive Care Medicine / Issue 8/2010
Print ISSN: 0342-4642
Electronic ISSN: 1432-1238
DOI
https://doi.org/10.1007/s00134-010-1887-4

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