Neutrophil gelatinase-associated lipocalin as a biomarker of cardiovascular disease: a systematic review
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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.
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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, 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, 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, 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.
Abstract
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.
About the authors
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.
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, 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, 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, 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.
©2012 by Walter de Gruyter Berlin Boston
Articles in the same Issue
- Masthead
- Masthead
- Editorials
- Neutrophil gelatinase-associated lipocalin (NGAL): the laboratory perspective
- Neutrophil gelatinase-associated lipocalin (NGAL): the clinician’s perspective
- Serum creatinine and the search for new biomarkers of acute kidney injury (AKI): the story continues
- Interference of new oral anticoagulants with frequently used coagulation tests
- Reviews
- Neutrophil gelatinase-associated lipocalin (NGAL) as biomarker of acute kidney injury: a review of the laboratory characteristics and clinical evidences
- Neurophil gelatinase-associated lipocalin as a new biomarker in laboratory medicine
- Neutrophil gelatinase-associated lipocalin as a biomarker of cardiovascular disease: a systematic review
- Opinion Paper
- Collective opinion paper on findings of the 2011 convocation of experts on laboratory quality
- Guidelines and Recommendations
- Proposals for the mitigation of the environmental impact of clinical laboratories
- General Clinical Chemistry and Laboratory Medicine
- Improvement in the performance of external quality assessment in Korean HIV clinical laboratories using unrecalcified human plasma
- Validation of a new generation POCT glucose device with emphasis on aspects important for glycemic control in the hospital care
- Evaluation of NGAL Test™, a fully-automated neutrophil gelatinase-associated lipocalin (NGAL) immunoassay on Beckman Coulter AU 5822
- Variation of serum and urinary neutrophil gelatinase associated lipocalin (NGAL) after strenuous physical exercise
- Analytic and clinical validation of a standardized cystatin C particle enhanced turbidimetric assay (PETIA) to estimate glomerular filtration rate
- Compensating for the influence of total serum protein in the Schwartz formula
- Interference of the new oral anticoagulant dabigatran with frequently used coagulation tests
- Testing for lupus anticoagulants – fresh or frozen?
- Effect of coagulation factors on discrepancies in International Normalized Ratio results between instruments
- Mobile Laboratory Unit: a disruptor solution for hemostasis management during major surgery. Usage in the context of face transplantation
- Comparison of capillary electrophoregram among heterozygous Hb Hope, Hb Hope/α-thalassemia-1 SEA type deletion and Hb Hope/β0-thalassemia
- Aberrant lamellar body counts noted on the Beckman Coulter Unicel DxH 800
- Plasma betaine concentrations correlate with plasma cortisol but not with C-reactive protein in an elderly population
- Determinants of the essential one-carbon metabolism metabolites, homocysteine, S-adenosylmethionine, S-adenosylhomocysteine and folate, in cerebrospinal fluid
- Application of a modified precipitation method for the measurement of small dense LDL-cholesterol (sd-LDL-C) in a population in southern Brazil
- Cancer Diagnostics
- BCR-ABL fusion protein detection in peripheral blood and bone marrow samples of adult precursor B-cell acute lymphoblastic leukemia patients using the flow cytometric immunobead assay
- Clinical and pathological features of B-cell non-Hodgkin lymphomas lacking the surface expression of immunoglobulin light chains
- Statistical learning confirms the diagnostic significance of the anemia panel in breast cancer
- Letters to the Editor
- Neutrophil gelatinase-associated lipocalin: comparison of the use of EDTA and heparin plasma
- Time- and temperature-dependent stability of troponin standard reference material 2921 in serum and plasma
- Triplex PCR amplicons genotyping by high resolution melting using Rotor Gene 6000 platform
- Effect of high RNA concentrations in real time reverse transcription quantitative polymerase chain reaction (RT-qPCR) yields
- Detection of differential protein expression in cerebrospinal fluid of patients with multiple sclerosis through two-dimensional differential in gel electrophoresis
- Phosphate inhibits calcium oxalate crystal growth and crystallization through reducing free calcium ions: a morphological analysis and calcium consumption assay
- Congress Abstracts
- 4th Slovenian Congress of Clinical Chemistry with international participation and 20th International Symposium of the Slovenian Association for Clinical Chemistry and Croatian Society of Medical Biochemists
- Congress of Clinical Chemistry and Laboratory Medicine / 9th Annual Meeting of the German Society for Clinical Chemistry and Laboratory Medicine (DGKL)
- Erratum
- Erratum to: Plasma betaine concentrations correlate with plasma cortisol but not with C-reactive protein in an elderly population
Articles in the same Issue
- Masthead
- Masthead
- Editorials
- Neutrophil gelatinase-associated lipocalin (NGAL): the laboratory perspective
- Neutrophil gelatinase-associated lipocalin (NGAL): the clinician’s perspective
- Serum creatinine and the search for new biomarkers of acute kidney injury (AKI): the story continues
- Interference of new oral anticoagulants with frequently used coagulation tests
- Reviews
- Neutrophil gelatinase-associated lipocalin (NGAL) as biomarker of acute kidney injury: a review of the laboratory characteristics and clinical evidences
- Neurophil gelatinase-associated lipocalin as a new biomarker in laboratory medicine
- Neutrophil gelatinase-associated lipocalin as a biomarker of cardiovascular disease: a systematic review
- Opinion Paper
- Collective opinion paper on findings of the 2011 convocation of experts on laboratory quality
- Guidelines and Recommendations
- Proposals for the mitigation of the environmental impact of clinical laboratories
- General Clinical Chemistry and Laboratory Medicine
- Improvement in the performance of external quality assessment in Korean HIV clinical laboratories using unrecalcified human plasma
- Validation of a new generation POCT glucose device with emphasis on aspects important for glycemic control in the hospital care
- Evaluation of NGAL Test™, a fully-automated neutrophil gelatinase-associated lipocalin (NGAL) immunoassay on Beckman Coulter AU 5822
- Variation of serum and urinary neutrophil gelatinase associated lipocalin (NGAL) after strenuous physical exercise
- Analytic and clinical validation of a standardized cystatin C particle enhanced turbidimetric assay (PETIA) to estimate glomerular filtration rate
- Compensating for the influence of total serum protein in the Schwartz formula
- Interference of the new oral anticoagulant dabigatran with frequently used coagulation tests
- Testing for lupus anticoagulants – fresh or frozen?
- Effect of coagulation factors on discrepancies in International Normalized Ratio results between instruments
- Mobile Laboratory Unit: a disruptor solution for hemostasis management during major surgery. Usage in the context of face transplantation
- Comparison of capillary electrophoregram among heterozygous Hb Hope, Hb Hope/α-thalassemia-1 SEA type deletion and Hb Hope/β0-thalassemia
- Aberrant lamellar body counts noted on the Beckman Coulter Unicel DxH 800
- Plasma betaine concentrations correlate with plasma cortisol but not with C-reactive protein in an elderly population
- Determinants of the essential one-carbon metabolism metabolites, homocysteine, S-adenosylmethionine, S-adenosylhomocysteine and folate, in cerebrospinal fluid
- Application of a modified precipitation method for the measurement of small dense LDL-cholesterol (sd-LDL-C) in a population in southern Brazil
- Cancer Diagnostics
- BCR-ABL fusion protein detection in peripheral blood and bone marrow samples of adult precursor B-cell acute lymphoblastic leukemia patients using the flow cytometric immunobead assay
- Clinical and pathological features of B-cell non-Hodgkin lymphomas lacking the surface expression of immunoglobulin light chains
- Statistical learning confirms the diagnostic significance of the anemia panel in breast cancer
- Letters to the Editor
- Neutrophil gelatinase-associated lipocalin: comparison of the use of EDTA and heparin plasma
- Time- and temperature-dependent stability of troponin standard reference material 2921 in serum and plasma
- Triplex PCR amplicons genotyping by high resolution melting using Rotor Gene 6000 platform
- Effect of high RNA concentrations in real time reverse transcription quantitative polymerase chain reaction (RT-qPCR) yields
- Detection of differential protein expression in cerebrospinal fluid of patients with multiple sclerosis through two-dimensional differential in gel electrophoresis
- Phosphate inhibits calcium oxalate crystal growth and crystallization through reducing free calcium ions: a morphological analysis and calcium consumption assay
- Congress Abstracts
- 4th Slovenian Congress of Clinical Chemistry with international participation and 20th International Symposium of the Slovenian Association for Clinical Chemistry and Croatian Society of Medical Biochemists
- Congress of Clinical Chemistry and Laboratory Medicine / 9th Annual Meeting of the German Society for Clinical Chemistry and Laboratory Medicine (DGKL)
- Erratum
- Erratum to: Plasma betaine concentrations correlate with plasma cortisol but not with C-reactive protein in an elderly population
