Neutrophil gelatinase-associated lipocalin (NGAL): a promising biomarker of contrast-induced nephropathy after computed tomography

Figures & data

Table 1. Principal biomarkers for early detection of AKI in humans.

Acronym/Abbreviation	Legend
AP	Alkaline phosphatase
α1MG	Alpha 1 microglobulin
β2MG	Beta 2 microglobulin
CarbHb	Carbamylated hemoglobin
CysC	Cystatin C
FENa	Fractional excretion of sodium
γGT	Gamma glutamyl transpeptidase
GST	Glutathione S transferase
HGF	Hepatocyte growth factor
IL-6	Interleukin 6
IL-8	Interleukin 8
IL-10	Interleukin 10
IL-18	Interleukin 18
KIM-1	Kidney injury molecule 1
LDH	Lactate dehydrogenase
L-FABP	Liver-type fatty acid-binding protein
MMP-9	Matrix metalloproteinase-9
NGAL	Neutrophil gelatinase-associated lipocalin
NAG	N-acetyl beta glucosaminidase
Neutrophil CD11b	Neutrophil CD11b
NHE3	Sodium hydrogen exchanger 3
RBP	Retinol binding protein
Pro-ANP	Prohormone of atrial natriuretic peptide
TNF-α	Tumor necrosis factor alpha
IGFBP7	Insulin-like growth factor-binding protein 7
TIMP-2	Tissue inhibitor of metalloproteinases-2

Figure 1. NGAL structure. Note: Permission is granted to copy, distribute and/or modify this document under the terms of the GNU Free Documentation License, Version 1.2 or any later version published by the Free Software Foundation; with no Invariant Sections, no Front-Cover Texts, and no Back-Cover Texts. A copy of the license is included in the section entitled GNU Free Documentation License. (From Wikipedia, the free encyclopedia.)

Figure 2. NGAL role in cellular physiology may be dependent on the type of molecule it is complexed with. Note: Apo-NGAL: NGAL that is devoid of siderophore or iron; ECM: extracellular matrix; VEGF: vascular endothelial growth factor; MMP-9: matrix metalloproteinase-9.

Table 2. NGAL as an AKI biomarker.

NGAL properties
Non-invasive, rapid, inexpensive method in urine or blood
Sensitive for early diagnosis
Amenable to existing clinical assay platforms
High gradient to allow risk stratification
Specific to AKI (AKI versus CKD vs. Systemic Disease)*
Differential diagnosis between pre-renal azotemia and AKI
The increase is proportional to injury or loss of renal function
Associated with a clear pathophysiological mechanism
Results predict clinical outcomes and treatment efficacy

Note: Plasma NGAL may be detected in chronic kidney disease (CKD), chronic hypertension, systemic infections, inflammatory conditions and malignancies.6,7 Urine NGAL may be detected in CKD, lupus nephritis and urinary tract infections.6,7 In all these situations, NGAL values are generally substantially blunted compared to those typically measured in AKI.

Table 3. Studies evaluating performance of NGAL and other biomarkers in CIN.

Study	Publication year	Biomarker	Administered contrast	U/P/S	Biomarker assay	CIN definition	Patients/ Events	AUC-ROC	PPV (%)	NPV (%)
Bachorzewska-Gajewska et al.16	2007	NGAL	IA	U S	ELISA^a	SCr >25% within 48 h	100/11	NA NA	NA NA	NA NA
Hirsch et al.18*	2007	NGAL	IA	U P	ELISA^a	SCr >50%	91/11	0.92 0.91	100 82	96 89
Ling et al.17	2008	NGAL	IA	U	ELISA^a	SCr >0.5 mg/dL or >25%	150/13	0.73	20	97
Shaker et al.19	2010	NGAL	IA	S	NA	SCr >25%	30/2	NA	NA	NA
Filiopoulos et al.25	2013	NGAL	IV	P	ELISA^b	SCr >0.5 mg/dL or >25% within 48 h	47/4	1.00	100	100
Lacquaniti et al.35	2013	NGAL	IV	S U	NA	NA	120/NA	0.99 0.99	NA NA	NA NA
Nakamura et al.38	2006	L-FABP	IA	U	Monoclonal Abs^a	SCr >0.5 mg/dL or >25% within 2–5 days	66/13	NA	NA	NA
Bachorzewska-Gajewska et al.41	2009	L-FABP	IA	U	ELISA^a	SCr >25% in 48 h	25/0	NA	NA	NA
Bulent Gul et al.39	2008	IL-18	IA	U	ELISA^a	SCr >0.5 mg/dL or >25%	157/15	NA	NA	NA
Ling et al.17	2008	IL-18	IA	U	ELISA^a	SCr >0.5 mg/dL or >25%	150/13	0.75	20	96
Bachorzewska-Gajewska et al.16	2007	CysC	IA	S	Nephelometric immunoassay^a	SCr >25% within 48 h	100/11	NA	NA	NA
Kato et al.40	2008	CysC	IA	S	Nephelometric immunoassay^a	SCr >0.5 mg/dL or >25% within 48 h	87/18	0.93	63	98
Briguori et al.42	2010	CysC	IA	S	Nephelometric immunoassay^a	SCr 0.3 mg/dL 48 h PP or RRT	410/34	0.92	39	100
Ishibashi et al.43	2010	CysC	IA	S	Nephelometric immunoassay^a	SCr >0.5 mg/dL or >25% within 48 h	100/18	>0.50	68	96
Shaker et al.19	2010	CysC	IA	S	NA	SCr >25%	30/2	NA	NA	NA

Notes: IA: intra-arterial, IV: intravenous, U: urine, P: plasma, S: serum, CIN: contrast-induced nephropathy, AUC-ROC: area under the receiver-operating characteristic curve, PPV: positive predictive value, NPV: negative predictive value, Abs: antibodies, SCr: serum creatinine, NA: not applicable or not available, NGAL: neutrophil gelatinase-associated lipocalin, ELISA: enzyme-linked immunosorbent assay, L-FABP: Liver-type fatty acid-binding protein, IL-18: interleukin 18, CysC: cystatin C, PP: post-procedure, RRT: renal replacement therapy.

^aResearch-based assay, ^bStandardized clinical laboratory platform (Triage kit [Biosite, San Diego, CA] or ARCHITECT platform [Abbott, Abbott Park, IL]).

*Study conducted in children.

Table 4. Urinary versus plasma/serum NGAL diagnostics.

	Pro	Contra
Urine	• Non-invasive nature of sample collection • Reduced number of interfering proteins • Potential for development of self-testing kits	• Lack of sample in case of oligoanuria • NGAL concentration may be influenced by hydration status or diuretic therapy or by co-existing urinary tract infection, as well as by co-existing CKD or in case of proteinuria
Plasma/Serum	• Sample available even in case of oligoanuria • Not influenced by hydration status or diuretic therapy or by co-existing urinary tract infection or proteinuria	• Invasive nature of sample collection • NGAL concentration may be influenced by co-existing CKD, hypertension, systemic infection, inflammatory conditions and malignancies

Note: NGAL: neutrophil gelatinase-associated lipocalin, CKD: chronic kidney disease.

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