Neutrophil Gelatinase-associated Lipocalin as a Cardiovascular Biomarker

Neutrophil gelatinase-associated lipocalin (NGAL) is a 25 kDa glycoprotein found in many tissues, and has attracted increasing attention as a biomarker for the early diagnosis of acute kidney injury (AKI). In the kidney, it is produced and released in response to ischaemic insults, and thus may also play a role in diagnostic and prognostic evaluation and management of patients with AKI, including those with acute cardiorenal syndromes. In the cardiovascular system, NGAL has been implicated in endothelial apoptosis and atherosclerosis, as well as in the thrombi associated with abdominal aortic aneurysms. This review explores the novel roles of NGAL in the cardiovascular system, and highlights some of the key research findings in this rapidly evolving field.

Download Full-text

Comparison of urine and serum neutrophil gelatinase-associated lipocalin after open and endovascular thoraco-abdominal aortic surgery and their meaning as indicators of acute kidney injury

VASA ◽

10.1024/0301-1526/a000736 ◽

2019 ◽

Vol 48 (1) ◽

pp. 79-87 ◽

Cited By ~ 4

Author(s):

Alexander Gombert ◽

Lukas Martin ◽

Ann Christina Foldenauer ◽

Clara Krajewski ◽

Andreas Greiner ◽

...

Keyword(s):

Acute Kidney Injury ◽

Serum Creatinine ◽

Kidney Injury ◽

Aortic Aneurysms ◽

Urine Ngal ◽

Neutrophil Gelatinase Associated Lipocalin ◽

Abdominal Aortic ◽

Potential Biomarker ◽

Significant Difference ◽

Neutrophil Gelatinase

Abstract. Background: Neutrophil gelatinase-associated lipocalin (NGAL) has been described as a potential biomarker of acute kidney injury (AKI) in different settings, but its behaviour under influence of open and endovascular repair of thoraco-abdominal aortic aneurysms (TAAA) has not been assessed yet. In this study, the course of NGAL was observed and differences of serum- (sNGAL) and urine-NGAL (uNGAL) levels following TAAA repair, especially with regard to AKI, were evaluated. Patients and methods: In this retrospective single centre study, 52 patients (mean age 64.5 years, [43–85 years]), including 39 (75 %) men, were enrolled (2014–2015, 13.2 months mean follow-up). Levels of sNGAL and uNGAL were measured perioperatively for 48 hours on intensive care unit. Twenty-three patients were treated by endovascular and 29 by open TAAA-repair. Results: Logistic regression revealed an increase in NGAL (sNGAL p = 0.0263, uNGAL p = 0.0080) corresponding with an increase in serum creatinine within the first 48 hours. Fourteen patients (26.9 %) developed AKI and 11 (21.1 %) required dialysis. The course of NGAL differed significantly (uNGAL p < .0001, sNGAL p = 0.0002) between patients suffering from AKI requiring dialysis and patients without AKI. The predictive power of uNGAL was three times higher than that of sNGAL (estimate of the regression slope 0.1382 vs. 0.0460). No significant difference between patients undergoing open or endovascular TAAA repair regarding the perioperative course of sNGAL and uNGAL was observed. Conclusion: serum-NGAL and urine-NGAL correlate with serum creatinine levels and AKI requiring dialysis. Furthermore, the postoperative course of sNGAL and uNGAL after open and endovascular TAAA repair is not significantly different. Taken together, the results indicate that uNGAL and, to a lesser extent, sNGAL could be considered biomarkers for early detection of perioperative AKI after open and endovascular TAAA surgery.

Download Full-text

Presence of NGAL/MMP-9 complexes in human abdominal aortic aneurysms

Thrombosis and Haemostasis ◽

10.1160/th06-11-0638 ◽

2007 ◽

Vol 98 (08) ◽

pp. 427-433 ◽

Cited By ~ 64

Author(s):

Chaoyong Zhu ◽

Angela Silveira ◽

Anne-Louise Hemdahl ◽

Anders Hamsten ◽

Ulf Hedin ◽

...

Keyword(s):

Elective Surgery ◽

Abdominal Aortic Aneurysms ◽

Aortic Aneurysms ◽

Intraluminal Thrombus ◽

Neutrophil Gelatinase Associated Lipocalin ◽

Reducing Conditions ◽

Aneurysm Wall ◽

Abdominal Aortic ◽

Aneurysm Growth ◽

Neutrophil Gelatinase

SummaryIt has been suggested that the intraluminal thrombus of abdominal aortic aneurysms (AAAs) predisposes for AAA enlargement and rupture.The growth of theAAA is dependent on proteolytic degradation of elastin. Here, we analysed whether the neutrophil gelatinase-associated lipocalin (NGAL) is expressed within the thrombus and the aneurysm wall. NGAL can bind to metalloproteinase- 9 (MMP-9) and inhibit its degradation,thereby preserving enzymatic activity. Biopsies were obtained from thrombus- free and thrombus-covered aneurysm wall and the intraluminal thrombus from patients undergoing elective surgery for AAA. Immunohistochemistry and real-time PCR were used to study NGAL and MMP-9 expression. Immunoprecipitation, gel zymography,Western blot and ELISA were used to detect and quantify NGAL/MMP-9 complexes. NGAL was detected in the thrombus, the interface between the thrombus and the underlying wall and in the wall itself.Double staining showed that neutrophils are the major source of NGAL expression. Immunoprecipitation of MMP-9 with antibody against NGAL showed that complexes of NGAL and active MMP-9 were present in thrombus, the interface fluid and the aneurysm wall.Western blot analyses using non-reducing conditions and gel zymography demonstrated that high-molecular-weight complexes of NGAL/MMP-9 were present within the different regions.The concentration of the NGAL/MMP-9 complex was highest in the luminal part of the thrombus. In conclusion, NGAL in complex with activated MMP-9 is present in AAA wall and thrombus. Neutrophil-derived NGAL could enhance the proteolytic activity associated with AAA, but the importance of this mechanism for aneurysm growth remains to be shown.

Download Full-text

The Potential Role of Neutrophil Gelatinase-Associated Lipocalin in the Development of Abdominal Aortic Aneurysms

Annals of Vascular Surgery ◽

10.1016/j.avsg.2018.11.006 ◽

2019 ◽

Vol 57 ◽

pp. 210-219 ◽

Cited By ~ 2

Author(s):

Menno E. Groeneveld ◽

Joyce A. Struik ◽

René J.P. Musters ◽

Geert J. Tangelder ◽

Pieter Koolwijk ◽

...

Keyword(s):

Potential Role ◽

Abdominal Aortic Aneurysms ◽

Aortic Aneurysms ◽

Neutrophil Gelatinase Associated Lipocalin ◽

Abdominal Aortic ◽

Neutrophil Gelatinase

Download Full-text

Clinical Application Neutrophil Gelatinase-Associated Lipocalin and Kidney Injury Molecule-1 as Indicators of Inflammation Persistence and Acute Kidney Injury in Children with Urinary Tract Infection

BioMed Research International ◽

10.1155/2013/947157 ◽

2013 ◽

Vol 2013 ◽

pp. 1-9 ◽

Cited By ~ 4

Author(s):

Stanislava Petrovic ◽

Natasa Bogavac-Stanojevic ◽

Amira Peco-Antic ◽

Ivana Ivanisevic ◽

Jelena Kotur-Stevuljevic ◽

...

Keyword(s):

Acute Kidney Injury ◽

Urinary Tract Infection ◽

Urinary Tract ◽

Tract Infection ◽

Kidney Injury ◽

The Novel ◽

Neutrophil Gelatinase Associated Lipocalin ◽

Significant Difference ◽

Kidney Injury Molecule 1 ◽

Neutrophil Gelatinase

Background. The aim of this study was to examine the novel renal biomarkers neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1) to assist pediatricians in the assessment of longer duration of inflammation and acute kidney injury (AKI) development during urinary tract infection (UTI).Methods. The patients enrolled in the study comprised 50 children (mean age was 6 months) with UTI. NGAL in serum and urine (sNGAL and uNGAL, resp.) and KIM-1 in urine were measured by enzyme-linked immunosorbent assays.Results. uNGAL levels in subjects with longer duration of inflammation were higher (115.37 ng/mL) than uNGAL levels in subjects with shorter duration of inflammation (67.87 ng/mL,P=0.022). Difference in sNGAL and KIM-1 levels was not significant (P=0.155andP=0.198, resp.). Significant difference was seen in KIM-1 excretion among groups with and without AKI (P=0.038). KIM-1 was not able to discriminate between subjects with and without AKI (area under the curves (AUC) = 0.620,P=0.175).Conclusions. uNGAL cannot be used for screening of the duration of inflammation during UTI. Accuracy of KIM-1 in screening of AKI development in children with UTI is low. We suggest larger studies to check the negative predictive value of KIM-1 for the development of AKI.

Download Full-text

Evaluation of urinary neutrophil gelatinase-associated lipocalin and urinary kidney injury molecule-1 as biomarkers of renal function in cancer patients treated with cisplatin

Journal of Oncology Pharmacy Practice ◽

10.1177/1078155220901756 ◽

2020 ◽

Vol 26 (7) ◽

pp. 1643-1649

Author(s):

Elliyeh Ghadrdan ◽

Sholeh Ebrahimpour ◽

Sanambar Sadighi ◽

Samira Chaibakhsh ◽

Zahra Jahangard-Rafsanjani

Keyword(s):

Acute Kidney Injury ◽

Serum Creatinine ◽

Characteristic Curve ◽

Kidney Injury ◽

Acute Kidney Injury Network ◽

The Novel ◽

Urinary Ngal ◽

Neutrophil Gelatinase Associated Lipocalin ◽

Kidney Injury Molecule 1 ◽

Neutrophil Gelatinase

Introduction Cisplatin-associated acute kidney injury (AKI) is the major limitation to the use of cisplatin-based chemotherapy regimens. Serum creatinine as a traditional marker did not increase in a timely enough fashion in AKI patients. Therefore, recently, the novel markers such as neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1) were considered for early detection of AKI. The aim of this study was to compare the sensitivity and specificity of urinary NGAL and KIM-1 with serum creatinine in cisplatin related AKI. Methods Patients ≥18 years with solid tumors who received cisplatin-based chemotherapy were included. Urine samples were collected 0, 6 and 24 h after cisplatin infusion and the urinary NGAL, KIM-1, and creatinine concentrations were evaluated. NGAL and KIM-1 concentrations were adjusted based on urine creatinine to eliminate hydration effects. Serum creatinine levels were assessed at the base and 72 h after cisplatin administration. Results Seven out of the 35 recruited patients (20%) suffered from AKI defined by Acute Kidney Injury Network criteria. In AKI patients, the ratio of urinary KIM-1–creatinine at 24 h compared to baseline (24 h/baseline) and NGAL–creatinine 24 h/baseline were significantly higher than those of non-AKI group ( p = 0.037 and 0.047 respectively). The area under the receiver-operating characteristic curve for KIM-1–creatinine 24 h/baseline and NGAL–creatinine 24 h/baseline were 0.78 (0.59–0.96, p = 0.032) and 0.77 (0.57–0.97, p = 0.036) respectively. Conclusions Our findings showed that the changes in urinary NGAL–creatinine and KIM-1–creatinine ratios, 24 h after cisplatin administration can be utilized to predict AKI in cisplatin recipients.

Download Full-text

Immediate postoperative plasma neutrophil gelatinase-associated lipocalin to predict acute kidney injury after major open abdominal aortic surgery: A prospective observational study

Anaesthesia Critical Care & Pain Medicine ◽

10.1016/j.accpm.2017.09.006 ◽

2018 ◽

Vol 37 (4) ◽

pp. 327-334

Author(s):

Philippe Guerci ◽

Jean-Louis Claudot ◽

Emmanuel Novy ◽

Nicla Settembre ◽

Jean-Marc Lalot ◽

...

Keyword(s):

Acute Kidney Injury ◽

Observational Study ◽

Prospective Observational Study ◽

Aortic Surgery ◽

Kidney Injury ◽

Abdominal Aortic Surgery ◽

Neutrophil Gelatinase Associated Lipocalin ◽

Abdominal Aortic ◽

Neutrophil Gelatinase

Download Full-text

Development of monoclonal antibodies and simplified sandwich ELISA for canine neutrophil gelatinase-associated lipocalin A detection

10.21203/rs.2.22511/v1 ◽

2020 ◽

Author(s):

Jun Cao ◽

Bo Tang ◽

Xinyu Zhang ◽

Xiaoli Xia ◽

Huaichang Sun

Keyword(s):

Monoclonal Antibodies ◽

Sandwich Elisa ◽

Kidney Injury ◽

The Novel ◽

E Coli ◽

Neutrophil Gelatinase Associated Lipocalin ◽

Hybridoma Cell Lines ◽

Neutrophil Gelatinase ◽

Canine Diseases ◽

Good Agreement

Abstract Background Acute kidney injury (AKI) is one of the most common canine diseases with a high mortality rate. Neutrophil gelatinase-associated lipocalin (NGAL) is the novel biomarker for early diagnosis of renal injury. Only few sandwich ELISA kits are commercially available, all of which require the use of expensive enzyme-conjugated secondary or biotinylated antibody. The aims of this study were to develop high affinity monoclonal antibodies (mAbs) and simplified sandwich ELISA for canine NGAL detection. Results Recombinant canine NGAL was expressed in E. coli and purified to a high purity. Six hybridoma cell lines were generated by immunization of mice with the purified protein, all of which secreted high titers of specific mAbs. By screening 36 different antibody combinations, a pair of mAbs with high additivity and P/N ratio was selected as the capture and detection antibodies. By conjugation of the detection mAb with horse radish peroxidase, a simplified sandwich ELISA was developed with a correlation coefficient of 0.9939, detection limit of 8.28 ng/mL. The parallel test of 42 samples from healthy and AKI dogs showed the good agreement in NGAL concentrations detected by the simplified sandwich ELISA and commercial ELISA kit. Conclusions We developed canine NGAL-specific monoclonal antibodies and simplified sandwich ELISA. The simplified sandwich ELISA could replace the commercial ELISA kits for canine NGAL detection with the advantages of reduced cost and detection time.

Download Full-text