Lab Med Online.  2014 Oct;4(4):191-197. 10.3343/lmo.2014.4.4.191.

Significance of Neutrophil Gelatinase-Associated Lipocalin Level as an Acute-Phase Reactant in Patients with Systemic Inflammatory Response Syndrome

• Je YS
• Choi JW
• Han SB
• Moon Y
• Lee JE

• KMID: 2312255
• DOI: http://doi.org/10.3343/lmo.2014.4.4.191

Abstract

BACKGROUND
We investigated the significance of plasma neutrophil gelatinase-associated lipocalin (pNGAL) level as an acute-phase reactant and an index for an increase in serum creatinine (sCr) level in patients with inflammatory diseases.
METHODS
A total of 63 patients with systemic inflammatory response syndrome (SIRS) and 149 without SIRS were evaluated, and pNGAL level was determined using a fluorescence immunoassay. sCr levels were measured daily during three days, and the difference between the initial and follow-up sCr levels was defined as a delta sCr value. Serum albumin/sCr ratio (sACR) was calculated. High-sensitivity C-reactive protein (hsCRP) level was determined using a latex turbidometric method.
RESULTS
The median pNGAL level in the SIRS group (154 ng/mL) was significantly higher than that in the non-SIRS (86 ng/mL) and control (62 ng/mL) groups (P<0.001, respectively). The area under the ROC curve (AUC) of pNGAL for diagnosing SIRS was 0.725 (95% CI, 0.664-0.781), which was not significantly different from that of hsCRP (0.749; 95% CI, 0.685-0.809; P=0.375). Multivariate regression analyses revealed that log-pNGAL was significantly associated with hsCRP (beta=0.546, P<0.001) and sACR (beta=0.351, P<0.001). The AUC of pNGAL for the positive delta sCr in 48-72 hr was 0.649 (95% CI, 0.542-0.746, P=0.023) in the SIRS group.
CONCLUSIONS
pNGAL is comparable to hsCRP as an inflammation-related parameter, and its measurement may provide additional information for a potential increase in sCr during 48-72 hr in patients with SIRS.

Keyword

Neutrophil gelatinase-associated lipocalin; Systemic inflammatory response syndrome; Acute-phase reactant

MeSH Terms

Area Under Curve
C-Reactive Protein
Creatinine
Fluorescence
Follow-Up Studies
Humans
Immunoassay
Latex
Lipocalins*
Neutrophils*
Plasma
ROC Curve
Systemic Inflammatory Response Syndrome*
C-Reactive Protein
Creatinine
Latex
Lipocalins

Figure

• 

  Fig. 1 The prevalence of an increase in pNGAL in SIRS and non-SIRS groups. The prevalence of pNGAL above the cutoff level (150 ng/mL) was significantly higher in the SIRS group than in the non-SIRS group (P<0.001). In particular, the proportion of patients showing pNGAL> 1,000 ng/mL was 6.3% in the SIRS group, but no patient showed pNGAL> 1,000 ng/mL in the non-SIRS group. Abbreviations: pNGAL, plasma neutrophil gelatinase-associated lipocalin; SIRS, systemic inflammatory response syndrome.

• 

  Fig. 2 Comparison of the ROC curve between pNGAL and hsCRP for the diagnosis of SIRS. The areas under the ROC curves (AUCs) for pNGAL and hsCRP were 0.725 (95% CI, 0.664-0.781) and 0.749 (95% CI, 0.685-0.809), respectively. No significant difference in the AUC was observed between the two parameters (P=0.375). Abbreviations: pNGAL, plasma neutrophil gelatinase-associated lipocalin; hsCRP, high-sensitivity C-reactive protein.

Reference

1. Flower DR, North AC, Attwood TK. Structure and sequence relationships in the lipocalins and related proteins. Protein Sci. 1993; 2:753–761.

2. 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(7019):917–921.

3. Clifton MC, Corrent C, Strong RK. Siderocalins: siderophore-binding proteins of the innate immune system. Biometals. 2009; 22:557–564.

4. Borregaard N, Cowland JB. Neutrophil gelatinase-associated lipocalin, a siderophore-binding eukaryotic protein. Biometals. 2006; 19:211–215.

5. 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; 18:407–413.

6. 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.

7. Clerico A, Galli C, Fortunato A, Ronco C. Neutrophil gelatinase-associated lipocalin (NGAL) as biomarker of acute kidney injury: a review of the laboratory characteristics and clinical evidences. Clin Chem Lab Med. 2012; 50:1505–1517.

8. Wu J, Ding Y, Zhu C, Shao X, Xie X, Lu K, et al. Urinary TNF-α and NGAL are correlated with the progression of nephropathy in patients with type 2 diabetes. Exp Ther Med. 2013; 6:1482–1488.

9. Bolignano D, Lacquaniti A, Coppolino G, Donato V, Fazio MR, Nicocia G, et al. Neutrophil gelatinase-associated lipocalin as an early biomarker of nephropathy in diabetic patients. Kidney Blood Press Res. 2009; 32:91–98.

10. Sahinarslan A, Kocaman SA, Bas D, Akyel A, Ercin U, Zengin O, et al. Plasma neutrophil gelatinase-associated lipocalin levels in acute myocardial infarction and stable coronary artery disease. Coron Artery Dis. 2011; 22:333–338.

11. Bagshaw SM, Bennett M, Haase M, Haase-Fielitz A, Egi M, Morimatsu H, 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.

12. Bone RC, Balk RA, Cerra FB, Dellinger RP, Fein AM, Knaus WA, et al. The ACCP/SCCM Consensus Conference Committee. American College of Chest Physicians/Society of Critical Care Medicine. Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. Chest. 1992; 101:1644–1655.

13. Haase M, Bellomo R, Devarajan P, Schlattmann P, Haase-Fielitz A. NGAL Meta-analysis Investigator Group. 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; 54:1012–1024.

14. Kim H, Hur M, Cruz DN, Moon HW, Yun YM. Plasma neutrophil gelatinase-associated lipocalin as a biomarker for acute kidney injury in critically ill patients with suspected sepsis. Clin Biochem. 2013; 46:1414–1418.

15. Kim SS, Song SH, Kim IJ, Yang JY, Lee JG, Kwak IS, et al. Clinical implication of urinary tubular markers in the early stage of nephropathy with type 2 diabetic patients. Diabetes Res Clin Pract. 2012; 97:251–257.

16. Martensson J, Bell M, Oldner A, Xu S, Venge P, Martling CR. Neutrophil gelatinase-associated lipocalin in adult septic patients with and without acute kidney injury. Intensive Care Med. 2010; 36:1333–1340.

17. Fujino RS, Tanaka K, Morimatsu M, Tamura K, Kogo H, Hara T. Spermatogonial cell-mediated activation of an IkappaBzeta-independent nuclear factor-kappaB pathway in Sertoli cells induces transcription of the lipocalin-2 gene. Mol Endocrinol. 2006; 20:904–915.

18. Xue JL, Daniels F, Star RA, Kimmel PL, Eggers PW, Molitoris BA, et al. Incidence and mortality of acute renal failure in Medicare beneficiaries, 1992 to 2001. J Am Soc Nephrol. 2006; 17:1135–1142.

19. Clec'h C, Gonzalez F, Lautrette A, Nguile-Makao M, Garrouste-Orgeas M, Jamali S, et al. Multiple-center evaluation of mortality associated with acute kidney injury in critically ill patients: a competing risks analysis. Crit Care. 2011; 15:R128.

20. Moran SM, Myers BD. Course of acute renal failure studied by a model of creatinine kinetics. Kidney Int. 1985; 27:928–937.

21. Al-Ismaili Z, Palijan A, Zappitelli M. Biomarkers of acute kidney injury in children: discovery, evaluation, and clinical application. Pediatr Nephrol. 2011; 26:29–40.

22. Devarajan P. Neutrophil gelatinase-associated lipocalin (NGAL): a new marker of kidney disease. Scand J Clin Lab Invest Suppl. 2008; 241:89–94.

23. Ronco C, Kellum JA, Haase M. Subclinical AKI is still AKI. Crit Care. 2012; 16(3):313.

24. Wang Y, Lam KS, Kraegen EW, Sweeney G, Zhang J, Tso AW, et al. Lipocalin-2 is an inflammatory marker closely associated with obesity, insulin resistance, and hyperglycemia in humans. Clin Chem. 2007; 53:34–41.

25. Xu SY, Pauksen K, Venge P. Serum measurements of human neutrophil lipocalin (HNL) discriminate between acute bacterial and viral infections. Scand J Clin Lab Invest. 1995; 55:125–131.

26. Bachorzewska-Gajewska H, Malyszko J, Sitniewska E, Malyszko JS, Dobrzycki S. Neutrophil gelatinase-associated lipocalin (NGAL) correlations with cystatin C, serum creatinine and eGFR in patients with normal serum creatinine undergoing coronary angiography. Nephrol Dial Transplant. 2007; 22:295–296.

27. 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; 94:661–666.