Soluble TWEAK independently predicts atherosclerosis in renal transplant patients

Türkmen, Kültiğin; Tonbul, Halil Zeki; Erdur, Fatih Mehmet; Toker, Aysun; Bıyık, Zeynep; Özbiner, Hüseyin; Gaipov, Abduzhappar; Gul, Elvin Enes; Kayrak, Mehmet; Solak, Yalçın; Özbek, Orhan; Türk, Süleyman; Covic, Adrian

doi:10.1186/1471-2369-14-144

Cited by 23 publications

(21 citation statements)

References 34 publications

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“…sTWEAK was negatively and independently associated with c-IMT in agreement with previous studies on asymptomatic subjects (13) and patients with CKD not on dialysis (28,29). However, positive association between sTWEAK and c-IMT has been reported in patients with transplants and CKD (30), which could be because of the presence of special therapy regimens used in patients with transplants and CKD.…”

Section: Discussionmentioning

confidence: 93%

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

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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.

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Section: Discussionmentioning

confidence: 93%

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

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“…Thus, c-IMT was inversely associated to sTWEAK in asymptomatic subjects [11] and in patients with chronic kidney disease [17e19]. However, this association has not been confirmed in other patient populations and, indeed, positive correlation between sTWEAK and c-IMT has been reported [20,21]. On the other hand, it has been reported that sTWEAK concentrations are negatively associated with flowmediated dilation (FMD) in patients with CKD, persisting after adjustment for factors related to FMD [17,22,23].…”

Section: Introductionmentioning

confidence: 92%

Soluble TWEAK levels predict the presence of carotid atherosclerotic plaques in subjects free from clinical cardiovascular diseases

et al. 2015

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“…Numerous low-powered cross-sectional ultrasound studies of carotid arteries have been performed in patients with renal transplants (28)(29)(30)(31)(32). The vast majority of these studies considered isolated biomarkers (mainly biomarkers of inflammation) (29,31,32) or just a limited set of purported risk factors. Longitudinal studies have several advantages over cross-sectional studies for exploring causation.…”

Section: Discussionmentioning

confidence: 99%

“…Among nonclassic risk factors, CRP (9) and biomarkers of CKD-MBD (10) undergo dramatic changes after transplantation, and FGF23 and 1,25(OH) 2 vitamin levels approach the normal range in most patients, whereas serum PTH often remains mildly to moderately elevated (27). Numerous low-powered cross-sectional ultrasound studies of carotid arteries have been performed in patients with renal transplants (28)(29)(30)(31)(32). The vast majority of these studies considered isolated biomarkers (mainly biomarkers of inflammation) (29,31,32) or just a limited set of purported risk factors.…”

Section: Discussionmentioning

confidence: 99%

A Longitudinal Study of Inflammation, CKD-Mineral Bone Disorder, and Carotid Atherosclerosis after Renal Transplantation

Yılmaz

Sönmez

Sağlam

et al. 2015

Clinical Journal of the American Society of Nephrology

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Background and objectives The role of reversibility of nontraditional risk factors, like inflammation and CKDmineral bone disorder, in the reduction of cardiovascular risk after renal transplantation is still scarcely defined.Design, setting, participants, and measurements The longitudinal relationship between C-reactive protein, CKDmineral bone disorder biomarkers, and intima media thickness was investigated in a series of 178 patients (age=32610 years) with stage 5 CKD maintained on chronic dialysis who underwent echo-color Doppler studies of the carotid arteries before and after renal transplantation. Smokers and patients with diabetes were excluded from the study. In all patients, immunosuppression was performed by a standard regimen on the basis of calcineurin inhibitors. Healthy controls were specifically selected to match the age and sex distribution of the patients. Biochemical and intima media thickness assessments were repeated 6 months after transplantation.Results Before transplantation, intima media thickness in patients with stage 5 CKD on dialysis (average=0.960.2 mm) was higher (P,0.001) than in well matched healthy controls (0.660.1 mm) and reduced substantially (222%; 95% confidence interval, 224% to 220%) after transplantation (P=0.001). GFR (multivariable-adjusted b=0.23; P,0.001), C-reactive protein (b=0.15; P,0.001), and fibroblast growth factor 23 (b=0.28; P,0.001) were the strongest independent correlates of intima media thickness before transplantation. Similarly, longitudinal changes in the same biomarkers were the sole independent correlates of simultaneous changes in intima media thickness (C-reactive protein: b=0.25; fibroblast growth factor 23: b=0.26; P,0.001 for both) after renal transplantation. The evolution of intima media thickness after transplantation was largely independent of classic risk factors, including BP, LDL cholesterol, and insulin resistance, as measured by homeostatic model assessment.Conclusions Intima media thickness improves after renal transplantation. Such an improvement associates with parallel changes in serum C-reactive protein and fibroblast growth factor 23. These observations are in keeping with the hypothesis that the decline in cardiovascular risk after transplantation, in part, depends on partial resolution of nontraditional cardiovascular risk factors, like inflammation and CKD-mineral bone disorder.

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Soluble TWEAK independently predicts atherosclerosis in renal transplant patients

Cited by 23 publications

References 34 publications

Soluble TWEAK and Major Adverse Cardiovascular Events in Patients with CKD

Soluble TWEAK and Major Adverse Cardiovascular Events in Patients with CKD

Soluble TWEAK levels predict the presence of carotid atherosclerotic plaques in subjects free from clinical cardiovascular diseases

A Longitudinal Study of Inflammation, CKD-Mineral Bone Disorder, and Carotid Atherosclerosis after Renal Transplantation

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