Plasma neutrophil gelatinase-associated lipocalin and risk of cardiovascular disease: Findings from the PREVEND prospective cohort study

Kunutsor, Setor K; Flores‐Guerrero, Jose L.; Kieneker, Lyanne M.; Nilsen, Turid; Hidden, Clara; Sundrehagen, Erling; Seidu, Samuel; Dullaart, Robin; Bakker, Stephan J. L.

doi:10.1016/j.cca.2018.07.034

Cited by 10 publications

(3 citation statements)

References 53 publications

(65 reference statements)

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“…Furthermore, when we additionally adjusted our Cox proportional hazards regression models for eGFR at baseline, statistically significant relationships were abrogated. This is in line with other studies showing kidney function-dependency of NGAL concentrations across different patient populations [40][41][42]. The intimate relationship between NGAL levels and eGFR is sustained by studies that have shown that NGAL may represent a reliable biomarker of the severity of renal impairment, i.e., could represent a surrogate marker of kidney damage [11,43,44].…”

Section: Discussionsupporting

confidence: 90%

Plasma Neutrophil Gelatinase-Associated Lipocalin Associates with New-Onset Chronic Kidney Disease in the General Population

et al. 2023

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Circulating levels of neutrophil gelatinase-associated lipocalin (NGAL) have been associated with acute kidney injury and the severity and progression of chronic kidney disease (CKD). This study investigated its potential utility as a biomarker for the risk of new-onset CKD in a population-based cohort study. Individuals without CKD at baseline (n = 4660) who participated in the Prevention of REnal and Vascular ENd-stage Disease (PREVEND) prospective population-based cohort study in the Netherlands were included. Baseline plasma NGAL concentrations were investigated for their associations with new-onset CKD, defined as a composite outcome of an estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2, urinary albumin excretion (UAE) > 30 mg/24-h, or both. Mean (±SD) plasma NGAL concentrations were 104.0 (±34.7) μg/L and median eGFR was 96 [IQR: 85.3–105.8] mL/min/1.73 m2. After median follow-up of 8.3 [IQR: 7.8–8.9] years, 467 participants developed new-onset CKD. Plasma NGAL concentrations were significantly associated with an increased risk of new-onset CKD (hazard ratio [HR] per doubling 1.35 [95% CI: 1.11–1.63], p = 0.002), even after adjustment for potentially confounding factors (1.37 [1.09–1.73], p = 0.007) except baseline eGFR (1.09 [0.86–1.37], p = 0.490). In secondary analyses, plasma NGAL concentrations were significantly associated with new-onset CKD as defined by eGFR < 60 mL/min/1.73 m2 alone (adjusted HR per doubling 2.54 [1.69–3.80], p < 0.001), which was abrogated after adjustment for eGFR (1.05 [0.69–1.59], p = 0.828), also when UAE > 30 mg/24-h was set as individual outcome (1.05 [0.82–1.35], p = 0.705). Higher plasma NGAL concentrations are associated with an increased risk of developing CKD in the general population. This association is dependent on renal function, and mainly driven by new-onset CKD as defined by renal function decline.

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Section: Discussionsupporting

confidence: 90%

Plasma Neutrophil Gelatinase-Associated Lipocalin Associates with New-Onset Chronic Kidney Disease in the General Population

et al. 2023

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“…25 Besides, neutrophil gelatinase associated lipocalin (NGAL) which is a 25 kDa protein that attach the granulocytes, it correlated with drug induced AKI since; it is responsible for the renal inflammation during ischemia thus; NGAL serum level be a sign of acute renal injury. 26 Additionally, different cytokines such as interleukin, interferon, and colony stimulating factors play an important and integral role in the renal tubular damage and repair so; they are considered as biomarkers of kidney injury during drug induced AKI. 27 Cystatin-c is a low molecular weight protein excreted by glomerular filtration and high level of Cystatin-c is linked with reduction of GFR and glomerular filtration.…”

Section: Biomarkers Of Acute Kidney Injurymentioning

confidence: 99%

Diclofenac induced-acute kidney injury is linked with oxidative stress and pro-inflammatory changes in Sprague Dawley rats

Al-Kuraishy

Al-Gareeb

Hussien

2019

J. Contemp. Med. Sci.

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Objectives: Diclofenac induces oxidative stress in the body and became the main cause of nephrotoxicity and acute kidney injury (AKI). The traditional markers of AKI are blood urea and serum creatinine which are regarded as low sensitive and low specific in detection the early renal damage. Therefore, the aim of present study was to evaluate oxidative stress and pro-inflammatory biomarkers in diclofenac induced- AKI in rats. Methods: Twenty Sprague Dawley Male rat were used and randomly divided in to 2 groups. Group1 (n=10): Rats treated with distilled water plus normal saline for 12 days. Group2 (n=10) : Rats treated with distilled water plus diclofenac 15mg/kg for 12 days. Rat body weight, body mass index and estimated glomerular filtration rate (eGFR) were evaluated in both groups. Blood urea, serum creatinine, serum malondialdehyde (MDA), superoxide dismutase (SOD), glutathione reductase (GSH), Neutrophil Gelatinase Associated Lipocalin (NGAL) , kidney injury molecules (KIM-1) and Cystatin-c were estimated. Results: Diclofenac 15mg/kg led to significant AKI through elevation of blood urea and serum creatinine with significant reduction of eGFR. KIM-1 serum level was significantly elevated with high sensitivity and specificity compared to the other tested biomarkers. Conclusion: KIM-1 serum level is more sensitive and specific with high accuracy compared to the other renal biomarkers in diclofenac induced- AKI. Estimation of KIM-1 serum levels should be regarded as a cornerstone for early detection of AKI in high risk patients.

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“…Our study has a larger sample size and can therefore reveal the significant association between LCN-2 and stroke risk in the general population. In the Prevention of Renal and Vascular End-stage Disease study, a non-linear relationship was observed between LCN-2 and the risk of CVD, but LCN-2 was not associated with stroke in this study in Caucasians [ 23 ]. The apparent disagreement with our study may be related to population characteristics.…”

Section: Discussionmentioning

confidence: 88%

Association of beta-2-microglobulin, cystatin C and lipocalin-2 with stroke risk in the general Chinese population

et al. 2023

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Introduction Beta-2-microglobulin (B2M), cystatin C and lipocalin-2 (LCN-2) are established renal biomarkers, yet their roles in stroke have not been fully evaluated. We aimed to investigate the relationship of B2M, cystatin C, and LCN-2 with stroke risk in a general Chinese population. Methods We used ordinal regression to study the relationship between serum B2M, cystatin C, and LCN-2 with stroke risk in 1060 participants (mean age 45.4 ± 10.8 years, 46% male) from the Shenzhen-Hong Kong United Network on Cardiovascular Disease (SHUN-CVD) study. Stroke risk was classified into low-risk, middle-risk and high-risk groups according to the China National Stroke Screening Survey criteria. Serum biomarker levels were measured using immunoturbidimetric assays. Participants with valid data on serum biomarker levels and stroke risk were included in the analysis. Results The number of participants in the low-risk, middle-risk and high-risk stroke risk groups were 663, 143 and 254 respectively. Elevated serum B2M, cystatin C, and LCN-2 levels were associated with being male, overweight/obesity, hypertension, alcohol consumption and smoking. Serum B2M, cystatin C and LCN-2 levels were significantly associated with stroke risk in the overall population (B2M: β = 0.595, p < .001; cystatin C: β = 3.718, p < .001; LCN-2: β = 0.564, p < .001) after adjustment for age. Conclusion Elevated serum B2M, cystatin C and LCN-2 levels are associated with stroke risk. They may be novel biomarkers for clinicians to assess stroke risk. Key messages Serum beta-2-microglobulin, cystatin C and lipocalin-2 levels are significantly associated with stroke risk. Beta-2-microglobulin, cystatin C and lipocalin-2 may serve as useful biomarkers for stroke risk stratification in the general population.

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Plasma neutrophil gelatinase-associated lipocalin and risk of cardiovascular disease: Findings from the PREVEND prospective cohort study

Abstract: Evidence suggests a non-linear association between NGAL and CVD risk, which is dependent on inflammation and renal function.

Cited by 10 publications

References 53 publications

Plasma Neutrophil Gelatinase-Associated Lipocalin Associates with New-Onset Chronic Kidney Disease in the General Population

Plasma Neutrophil Gelatinase-Associated Lipocalin Associates with New-Onset Chronic Kidney Disease in the General Population

Diclofenac induced-acute kidney injury is linked with oxidative stress and pro-inflammatory changes in Sprague Dawley rats

Association of beta-2-microglobulin, cystatin C and lipocalin-2 with stroke risk in the general Chinese population

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