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Clinical Chemistry and Laboratory Medicine (CCLM)

Published in Association with the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM)

Editor-in-Chief: Plebani, Mario

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Volume 50, Issue 9 (Sep 2012)


Neutrophil gelatinase-associated lipocalin as a biomarker of cardiovascular disease: a systematic review

Dinna N. Cruz
  • Corresponding author
  • Department of Nephrology Dialysis and Transplantation, San Bortolo Hospital, Vicenza, Italy
  • International Renal Research Institute (IRRIV), Vicenza, Italy
  • Email
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Sergio Gaiao
  • Nephrology Research and Development Unit, Faculty of Medicine, University of Porto, Hospital de São João, Porto, Portugal
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Alan Maisel
  • Department of Medicine and Cardiology, San Diego VA Medical Center and University of California, San Diego, CA, USA
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Claudio Ronco
  • Department of Nephrology Dialysis and Transplantation, San Bortolo Hospital, Vicenza, Italy
  • International Renal Research Institute (IRRIV), Vicenza, Italy
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Prasad Devarajan
  • Division of Nephrology and Center for Acute Care Nephrology, Cincinnati Children’s Hospital Medical Center, University of Cincinnati School of Medicine, Cincinnati, OH, USA
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
Published Online: 2012-07-07 | DOI: https://doi.org/10.1515/cclm-2012-0307


Background: Neutrophil gelatinase-associated lipocalin (NGAL) is a biomarker of acute kidney injury (AKI). Recently, elevated NGAL levels have also been reported in heart failure, coronary heart disease, and stroke. Other studies demonstrate that NGAL is upregulated in failing myocardium and in atherosclerotic plaque. Our aim was to synthesize the current evidence on NGAL and cardiovascular disease (CVD), and to clarify the prognostic significance of systemic NGAL levels in CVD.

Methods: We performed a systematic review to identify experimental and human studies on NGAL and CVD. We excluded articles which specifically dealt with AKI or renal endpoints.

Results: We identified 22 studies, including both animal and human data. NGAL is highly expressed in the heart, both in failing myocardium and myocarditis, and is also expressed in atherosclerotic plaques. Areas of co-localization of NGAL and matrix metalloproteinase (MMP)-9 exhibited increased MMP-9 proteolytic activity. Systemic NGAL levels correlated with renal function and severity of CVD in several, but not all, studies. An association between elevated systemic NGAL levels and clinical outcomes (e.g., death, hospital readmissions) were reported in six CVD studies, but these had limited adjustment for potential confounders.

Conclusions: There is ample literature to support a putative role of NGAL in the pathophysiology of CVD, but at present there is insufficient data regarding the clinical utility of systemic NGAL levels in the management of CVD. Available evidence regarding NGAL as a predictor of outcomes in CVD is very limited.

This article offers supplementary material which is provided at the end of the article.

Keywords: atherosclerosis; biomarkers; brain natriuretic peptide (BNP); cardiovascular disease; cerebrovascular disease; coronary artery disease; heart failure; matrix metalloproteinase; myocarditis; neutrophil gelatinase associated lipocalin (NGAL); stroke

About the article

Dinna N. Cruz

Dinna N. Cruz, MD, MPH, is Director for Research at the Department of Nephrology, Dialysis and Transplantation at San Bortolo Hospital and the International Renal Research Institute Vicenza (IRRIV) in Vicenza, Italy. As a nephrologist and epidemiologist, her research interests and expertise include extracorporeal blood purification techniques, acute kidney injury and the cardio-renal syndromes. She has authored over several peer-reviewed publications on various aspects of renal and cardiorenal disease in prestigious international journals and has contributed chapters to key international nephrology textbooks. She serves as Associate Editor for Blood Purification and Clinical Kidney Journal and as a reviewer for a number of high ranking Nephrology, ICU, and Internal Medicine journals.

Sergio Gaiao

Sérgio Gaião, MD is a nephrologist and is currently working at the General Intensive Care Unit in Hospital São João, Porto, Portugal. During his nephrology training, he did a research fellowship with the International Renal Research Institute of Vicenza (IRRIV). He also lectures in Critical Care Nephrology at the Faculty of Medicine, University of Porto. He is dedicated to clinical research, specifically biomarkers of acute kidney injury and renal replacement therapy, in part in collaboration with IRRIV.

Alan Maisel

Alan Maisel, MD, is a Professor of Medicine at the University of California, San Diego. He is the Director of the Coronary Care Unit and Heart Failure Program at the VA San Diego Healthcare System in La Jolla, California. He is an associate editor of the Journal of the American College Cardiology. Dr. Maisel is considered one of the world’s experts on cardiac biomarkers and has over 150 scientific publications. He has authored several ground-breaking publications that have paved the way for the development of diagnostic tools for patients with congestive heart failure.

Claudio Ronco

Claudio Ronco, MD, is Director of the Department of Nephrology, Dialysis and Transplantation at San Bortolo Hospital and the International Renal Research Institute Vicenza (IRRIV) in Vicenza, Italy. He is Editor-in-Chief of Blood Purification and the former President of the International Society for Hemodialysis (ISHD). He is a member of the council of several scientific societies. He has co-authored 650 papers, 36 book chapters, 45 books and seven monographic journal issues and has delivered more than 450 lectures at international meetings and universities.

Prasad Devarajan

Prasad Devarajan, MD, is the Williams Endowed Chair, Professor of Pediatrics and Developmental Biology, Director of Nephrology and Hypertension, Director of Clinical Laboratories, and CEO of the Dialysis Unit at Cincinnati Children’s Hospital Medical Center and University of Cincinnati. He has authored over 200 peer-reviewed publications. He has been continuously funded by the National Institutes of Health and several other foundations for more than 25 years. His major research interests lie in using proteomic and functional genomic approaches for the discovery of pathogenetic pathways, diagnostic biomarkers, and novel therapies of acute kidney injury and chronic kidney disease. His laboratory has pioneered the discovery, translation, and validation of NGAL as a biomarker of acute kidney injury.

Corresponding author: Dinna N. Cruz, MD, MPH, Department of Nephrology, San Bortolo Hospital, Viale Rodolfi 37, 36100 Vicenza, Italy Phone: +39 0444 753650, Fax: +39 0444 753973

Received: 2012-05-15

Accepted: 2012-05-30

Published Online: 2012-07-07

Published in Print: 2012-09-01

Citation Information: Clinical Chemistry and Laboratory Medicine (CCLM), ISSN (Online) 1437-4331, ISSN (Print) 1434-6621, DOI: https://doi.org/10.1515/cclm-2012-0307.

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