Serum levels of the atherosclerosis biomarker sTWEAK are decreased in type 2 diabetes and end-stage renal disease

Kralisch, Susan; Ziegelmeier, Michaela; Bachmann, Anette; Seeger, Jeannette; Lössner, Ulrike; Blüher, Matthias; Stümvoll, Michael; Faßhauer, Mathias

doi:10.1016/j.atherosclerosis.2007.10.022

Cited by 92 publications

(87 citation statements)

References 12 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…At the same time, we showed for the first time an independent relationship between sTWEAK levels and ED in 295 patients with CKD. These results therefore agree with previous reports on diminution in sTWEAK plasma levels in patients with CKD (26) and in HD patients (19).…”

Section: Discussionsupporting

confidence: 83%

Soluble TWEAK Plasma Levels as a Novel Biomarker of Endothelial Function in Patients with Chronic Kidney Disease

Yılmaz¹,

Carrero²,

Ortíz³

et al. 2009

Clinical Journal of the American Society of Nephrology

View full text Add to dashboard Cite

Background and objectives: Recently, we showed that soluble TNF-like weak inducer of apoptosis (sTWEAK) plasma levels are diminished in hemodialysis patients and had additive effects with IL-6 on survival. Because sTWEAK plasma level has been associated with the presence of chronic kidney disease (CKD) and cardiovascular disease, we hypothesized that in patients with CKD, sTWEAK levels may relate to the increased prevalence of endothelial dysfunction that usually accompanies the decline of estimated GFR (eGFR).Design, setting, participants, & measurements: We studied 295 patients with different stages of nondiabetic CKD (52% male; age 47 ؎ 12 yr), testing the association between sTWEAK plasma levels and CKD stage and the relationship between flow-mediated dilation (FMD) and sTWEAK concentrations. Fifty-five healthy volunteers (51% male; age 47 ؎ 11 yr) served as matched control subjects.Results: A gradual decrease in FMD was observed as eGFR decreased. Compared with healthy control subjects, sTWEAK plasma levels were diminished in all stages of CKD and correlated strongly with eGFR. FMD levels were associated with sTWEAK concentrations in univariate analysis. This association persisted after multivariate adjustment for eGFR levels, high-sensitivity C-reactive protein, diastolic BP, and sTWEAK, all of which were found to be significant and independent contributors to FMD.Conclusions: A decline in eGFR is accompanied by gradual reductions in sTWEAK plasma levels. Because sTWEAK strongly and independently correlated with FMD, our study suggests novel links between sTWEAK and endothelial dysfunction in patients with CKD.

show abstract

Section: Discussionsupporting

confidence: 83%

Soluble TWEAK Plasma Levels as a Novel Biomarker of Endothelial Function in Patients with Chronic Kidney Disease

Yılmaz¹,

Carrero²,

Ortíz³

et al. 2009

Clinical Journal of the American Society of Nephrology

View full text Add to dashboard Cite

show abstract

“…However, patients with CKD exhibit lower levels of sTWEAK than healthy controls (23). Whether TWEAK plays a role in the inflammation-atherosclerosis axis present in CKD currently remains unknown.…”

mentioning

confidence: 99%

Additive Effects of Soluble TWEAK and Inflammation on Mortality in Hemodialysis Patients

Carrero

Ortíz

Qureshi

et al. 2009

Clinical Journal of the American Society of Nephrology

106

View full text Add to dashboard Cite

Background and objectives: Chronic kidney disease (CKD) is characterized by an exceptionally high mortality rate, primarily due to cardiovascular disease. Reduced soluble TNF-like weak inducer of apoptosis (sTWEAK) plasma levels have been reported both in patients with subclinical atherosclerosis and CKD.Design, participants, & measurements: A cross-sectional study was conducted in 218 prevalent patients (121 men; 63 ؎ 14 yr) undergoing hemodialysis (HD). sTWEAK levels in relation with the patients' outcome were studied.Results: sTWEAK plasma levels were 208 [(165 to 272) pg/ml, median interquartile range], significantly lower than healthy controls (P < 0.0001). sTWEAK was negatively associated with inflammatory markers, such as C-reactive protein and IL-6. Overall mortality was assessed after an average follow-up of 31 mo, during which 81 patients died. After controlling for potential confounding variables, patients in the upper tertile of sTWEAK plasma levels had an increased risk of cardiovascular and all-cause mortality. A significant interaction effect between sTWEAK and IL-6 levels was found [synergy index: 2.19 (0.80, 5.93)]. Thus, the association of sTWEAK with mortality was strongest in patients with inflammation (defined as IL-6 > 7.0 pg/ml), in whom high sTWEAK strongly predicted cardiovascular and all-cause mortality. These results were confirmed in a second cohort of HD patients.Conclusions: The concurrent presence of elevated sTWEAK plasma concentrations and an inflammatory environment have additive effects on mortality in HD patients. Further studies on the potential different role of sTWEAK in health and disease are warranted.

show abstract

“…After that, the association of sTWEAK with CVD or CVD-related diseases has been extensively studied. sTWEAK concentrations are diminished in patients with coronary artery disease (14), abdominal aortic aneurysm (15), systolic heart failure (16), type 2 diabetes (17), and CKD (18).…”

Section: Introductionmentioning

confidence: 99%

Soluble TWEAK and Major Adverse Cardiovascular Events in Patients with CKD

Fernández‐Laso

Sastre

Valdivielso

et al. 2016

Clinical Journal of the American Society of Nephrology

View full text Add to dashboard Cite

Background and objectives Soluble TNF-like weak inducer of apoptosis (sTWEAK) is a proinflammatory cytokine belonging to the TNF superfamily. sTWEAK concentrations have been associated with the presence of CKD and cardiovascular disease (CVD). We hypothesized that sTWEAK levels may relate to a higher prevalence of atherosclerotic plaques, vascular calcification, and cardiovascular outcomes observed in patients with CKD.Design, setting, participants, & measurements A 4-year prospective, multicenter, longitudinal study was conducted in 1058 patients with CKD stages 3-5D (mean age =58613 years old; 665 men) but without any history of CVD from the NEFRONA Study (a study design on the prevalence of surrogate markers of CVD). Anklebrachial index and B-mode ultrasound were performed to detect the presence of carotid and/or femoral atherosclerotic plaques together with biochemical measurements and sTWEAK assessment. Patients were followed for cardiovascular outcomes (follow-up of 3.1361.15 years).Results Patients with more advanced CKD had lower sTWEAK levels. sTWEAK concentrations were independently and negatively associated with carotid intima-media thickness. sTWEAK levels were lower in patients with carotid atherosclerotic plaques but not in those with femoral plaques. After adjustment by confounders, the odds ratio (OR) for presenting carotid atherosclerotic plaques in patients in the lowest versus highest tertile of sTWEAK was 4.18 (95% confidence interval [95% CI], 2.89 to 6.08; P,0.001). Furthermore, sTWEAK levels were lower in patients with calcified carotid atherosclerotic plaques. The OR for presenting calcified carotid plaques was 1.77 (95% CI, 1.06 to 2.93; P=0.02) after multivariable adjustment. After the followup, 41 fatal and 68 nonfatal cardiovascular events occurred. In a Cox model, after controlling for potential confounding factors, patients in the lowest tertile of sTWEAK concentrations had a higher risk of fatal and nonfatal cardiovascular events (hazard ratio [HR], 2.40; 95% CI, 1.33 to 4.33; P=0.004) and cardiovascular mortality (HR, 2.67; 95% CI, 1.05 to 6.76; P=0.04).Conclusions Low sTWEAK levels were associated with the presence of carotid atherosclerotic plaques in patients with CKD. Additionally, lower sTWEAK levels were associated with a higher risk of cardiovascular morbidity and mortality.

show abstract

Serum levels of the atherosclerosis biomarker sTWEAK are decreased in type 2 diabetes and end-stage renal disease

Cited by 92 publications

References 12 publications

Soluble TWEAK Plasma Levels as a Novel Biomarker of Endothelial Function in Patients with Chronic Kidney Disease

Soluble TWEAK Plasma Levels as a Novel Biomarker of Endothelial Function in Patients with Chronic Kidney Disease

Additive Effects of Soluble TWEAK and Inflammation on Mortality in Hemodialysis Patients

Soluble TWEAK and Major Adverse Cardiovascular Events in Patients with CKD

Contact Info

Product

Resources

About