Serum neutrophil gelatinase-associated lipocalin is associated with cardiovascular events in patients with chronic kidney disease.
BACKGROUND
Neutrophil gelatinase-associated lipocalin (NGAL) is a member of the lipocalin family best known as a novel and early marker of acute kidney injury (AKI). Recent data suggest that NGQueryAL is not only a marker of AKI, but also an important player in the vascular remodeling, atherosclerotic plaque stability and thrombus formation. We conducted this study to investigate the association of serum NGAL levels with fatal and composite (fatal and non-fatal) cardiovascular events (CVE) in a cohort of patients with stage 1-5 CKD.


METHODS
This was an observational cohort study in which serum NGAL was obtained from 298 CKD (stages 1-5) patients. Fatal and composite CVE were recorded for a median 41 months. We examined alteration of serum NGAL through CKD groups as well as association with inflammatory markers. We also performed a Cox regression analysis to determine the association of NGAL with predefined clinical outcomes.


RESULTS
The median value of NGAL was 50.5 ng/mL (IR 47.6-54.9 ng/mL), and higher NGAL values were recorded in diabetic patients. In a multiple linear regression model, including all univariate associates of NGAL, only log eGFR, log hs-CRP and log HDL cholesterol maintained an independent association with log NGAL. During the observational period, 30 patients died due to cardiovascular causes and 69 non-fatal CVE were registered. In the fully adjusted model, we observed a 2.08-fold increase in the risk of fatal CVE and a 1.50-fold increase in the risk of fatal and non-fatal CVE for each increment of 1 SD in log NGAL values.


CONCLUSIONS
This is the first study that shows that serum NGAL is associated with cardiovascular events (fatal and non-fatal) in patients with CKD, independently of traditional risk factors, renal function and inflammation.
Division of Nephrology, Department of Internal Medicine, Sakarya University Medical School, Sakarya, Turkey. yalcinsolakmd@gmail.com.
Yalcin
Y
Solak
Department of Nephrology, Gülhane School of Medicine, Ankara, Turkey.
Mahmut Ilker
MI
Yilmaz
Nephrology Clinic, Dialysis and Renal Transplant Center, 'C.I. PARHON' University Hospital, and 'Grigore T. Popa' University of Medicine, Iasi, Romania.
Dimitrie
D
Siriopol
Department of Radiology, Gülhane School of Medicine, Ankara, Turkey.
Mutlu
M
Saglam
Department of Nephrology, Gülhane School of Medicine, Ankara, Turkey.
Hilmi Umut
HU
Unal
Department of Biochemistry, Gülhane School of Medicine, Ankara, Turkey.
Halil
H
Yaman
Department of Nephrology, Gülhane School of Medicine, Ankara, Turkey.
Mahmut
M
Gok
Department of Nephrology, Gülhane School of Medicine, Ankara, Turkey.
Hakki
H
Cetinkaya
Department of Extracorporeal Hemocorrection, National Scientific Medical Research Center, Astana, Kazakhstan.
Abduzhappar
A
Gaipov
Department of Nephrology, Gülhane School of Medicine, Ankara, Turkey.
Tayfun
T
Eyileten
Nephrology Clinic, Dialysis and Renal Transplant Center, 'C.I. PARHON' University Hospital, and 'Grigore T. Popa' University of Medicine, Iasi, Romania.
Sebahattin
S
Sari
Department of Emergency, Gulhane School of Medicine, Ankara, Turkey.
Ali Osman
AO
Yildirim
Department of Nephrology, Necmettin Erbakan University Meram School of Medicine, Konya, Turkey.
Halil Zeki
HZ
Tonbul
Division of Nephrology, Department of Internal Medicine, Selcuk University School of Medicine, Konya, Turkey.
Suleyman
S
Turk
Nephrology Clinic, Dialysis and Renal Transplant Center, 'C.I. PARHON' University Hospital, and 'Grigore T. Popa' University of Medicine, Iasi, Romania.
Adrian
A
Covic
Division of Nephrology, Department of Medicine, Koc University School of Medicine, Istanbul, Turkey.
Mehmet
M
Kanbay
D000209:Acute-Phase Proteins; D000328:Adult; D019540:Area Under Curve; D002097:C-Reactive Protein / Q000378:metabolism; D002318:Cardiovascular Diseases / Q000097:blood* / Q000453:epidemiology / Q000401:mortality; D008076:Cholesterol, HDL / Q000097:blood; D003327:Coronary Disease / Q000453:epidemiology; D016757:Death, Sudden, Cardiac / Q000453:epidemiology; D003920:Diabetes Mellitus / Q000097:blood; D005260:Female; D005919:Glomerular Filtration Rate; D006801:Humans; D016014:Linear Models; D000071068:Lipocalin-2; D054834:Lipocalins / Q000097:blood*; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000097:blood / Q000453:epidemiology; D058729:Peripheral Arterial Disease / Q000097:blood / Q000453:epidemiology; D015995:Prevalence; D016016:Proportional Hazards Models; D011446:Prospective Studies; D011518:Proto-Oncogene Proteins / Q000097:blood*; D012372:ROC Curve; D051436:Renal Insufficiency, Chronic / Q000097:blood* / Q000503:physiopathology; D020521:Stroke / Q000453:epidemiology
D000209:Acute-Phase Proteins; D008076:Cholesterol, HDL; C489506:LCN2 protein, human; D000071068:Lipocalin-2; D054834:Lipocalins; D011518:Proto-Oncogene Proteins; D002097:C-Reactive Protein
Cardiovascular disease; Chronic kidney disease; Mortality; NGAL; Prediction