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Clinical Chemistry and Laboratory Medicine (CCLM)

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

1, 2 / Sergio Gaiao3 / Alan Maisel4 / Claudio Ronco1, 2 / Prasad Devarajan5

1Department of Nephrology Dialysis and Transplantation, San Bortolo Hospital, Vicenza, Italy

2International Renal Research Institute (IRRIV), Vicenza, Italy

3Nephrology Research and Development Unit, Faculty of Medicine, University of Porto, Hospital de São João, Porto, Portugal

4Department of Medicine and Cardiology, San Diego VA Medical Center and University of California, San Diego, CA, USA

5Division of Nephrology and Center for Acute Care Nephrology, Cincinnati Children’s Hospital Medical Center, University of Cincinnati School of Medicine, Cincinnati, OH, USA

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

Citation Information: Clinical Chemistry and Laboratory Medicine (CCLM). Volume 50, Issue 9, Pages 1533–1545, ISSN (Online) 1437-4331, ISSN (Print) 1434-6621, DOI: https://doi.org/10.1515/cclm-2012-0307, July 2012

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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.

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

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