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Overview of Neutrophil Gelatinase-Associated Lipocalin (NGAL) as a Biomarker in Nephrology

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Biomarkers in Kidney Disease

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Abstract

Neutrophil gelatinase-associated lipocalin (NGAL) is a small 25-kD peptide belonging to the lipocalin superfamily. It mainly binds to siderophores, iron-carrying molecules which are essential to bacterial and eukaryotic cells to meet their needs of this mineral and then ensure survival. Indeed, NGAL primarily acts as an innate nonspecific antibacterial factor, since it prevents bacteria to internalize iron thus inhibiting their growth. However, serum NGAL levels rise not only in the course of infective processes but also in other pathological conditions, as the result of an increased production and release from several tissues after an injury. Numerous experimental and clinical data support a role for NGAL as a biomarker in nephrology. It has been demonstrated that NGAL predicts the onset of acute kidney injury (AKI), closely correlates with the extent of renal impairment in patients with chronic kidney disease (CKD) irrespective of the underlying renal disease; it is higher in kidney transplant patients who will develop a delayed graft function (DGF) compared to those who will not experience this complication. Furthermore, NGAL predicts CKD progression and may represent a precocious marker of therapeutic response in different clinical situations. A number of studies also established the involvement of this molecule in carcinogenesis and progression of several human tumors, in the regulation of erythropoiesis and in the pathophysiology of cardiovascular diseases. The aim of the present review has been therefore to summarize all the most recent findings concerning the potential use of NGAL as a diagnostic and prognostic marker as well as a marker of therapeutic response in patients with renal diseases.

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Abbreviations

ADPKD:

Autosomal-dominant polycystic kidney disease

AKI:

Acute kidney injury

CIN:

Contrast-induced nephropathy

CKD:

Chronic kidney disease

CPB:

Cardiopulmonary bypass

CT:

Computed tomography

DGF:

Delayed graft function

ESRD:

End-stage renal disease

FABP:

Fatty acid-binding protein

FeNGAL:

Fractional excretion of NGAL

GFR:

Glomerular filtration rate

KIM-1:

Kidney injury molecule-1

NAG:

N-acetyl-β-d-glucosaminidase

NGAL:

Neutrophil gelatinase-associated lipocalin

PCI:

Percutaneous coronary intervention

shRNA:

Short hairpin RNA

sNGAL:

Serum NGAL

uNGAL:

Urinary NGAL

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Authors and Affiliations

  1. Department of Clinical and Experimental Medicine, University of Messina, Via Consolare Valeria n.1, 98124, Messina, Italy

    Valeria Cernaro, Antoine Buemi, Antonio Lacquaniti, Domenico Santoro & Michele Buemi

  2. CNR – Institute of Clinical Physiology, c/o EUROLINE, Via Vallone Petrara 55-57, 89124, Reggio Calabria, Italy

    Davide Bolignano

Authors
  1. Valeria Cernaro
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  2. Davide Bolignano
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  3. Antoine Buemi
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  4. Antonio Lacquaniti
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  5. Domenico Santoro
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  6. Michele Buemi
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Correspondence to Michele Buemi .

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  1. Department of Biomedical Sciences, University of Westminster, London, United Kingdom

    Vinood B. Patel

Definitions

Acute kidney injury (AKI)

Sudden decline, from 1 to 7 days, of renal function with retention of nitrogen products (urea, creatinine), metabolic acidosis, hyperkalemia, salt and water retention, decreased urine flow, and anuria.

Autosomal-dominant polycystic kidney disease (ADPKD)

The most common hereditary renal disease; it is characterized by the progressive cystic dilatation of renal tubules with volume increase of the kidneys and gradual progression to end-stage renal disease.

Biomarker

Molecular substance or characteristic that can be used as an indicator in a living organism. Its presence, absence, or modification, detectable and quantifiable using appropriate tests, are the expression of a normal or pathological biological process or the response to a certain pharmacological treatment.

Cold ischemia time

Time elapsed between the start of perfusion with cold solutions in the explantation operating room and the extraction of the organ from the ice in which it is preserved (or from other refrigerated systems of preservation) at the moment of transplantation.

Contrast-induced nephropathy (CIN)

Absolute (≥0.5 mg/dl) or relative increase (≥25 %) in serum creatinine level at 48–72 h after exposure to a contrast agent compared to serum creatinine at baseline.

Delayed graft function

Dialysis requirement during the first week after kidney transplantation.

Siderophores

Iron-carrying molecules which are essential to bacterial and eukaryotic cells to meet their needs of this mineral and then ensure survival.

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Cernaro, V., Bolignano, D., Buemi, A., Lacquaniti, A., Santoro, D., Buemi, M. (2015). Overview of Neutrophil Gelatinase-Associated Lipocalin (NGAL) as a Biomarker in Nephrology. In: Patel, V. (eds) Biomarkers in Kidney Disease. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-7743-9_16-1

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