Soluble CD154 Is a Unique Predictor of Nonfatal and Fatal Atherothrombotic Events in Patients Who Have End-Stage Renal Disease and Are on Hemodialysis

Hocher, Berthold; Liefeldt, Lutz; Quaschning, Thomas; Kalk, Philipp; Ziebig, Reinhard; Godes, Michael; Relle, Katharina; Asmus, G.; Stasch, Johannes-Peter

doi:10.1681/asn.2006070684

Cited by 17 publications

(13 citation statements)

References 38 publications

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“…In asymptomatic patients with low-grade carotid stenosis, increased sCD40L concentrations predict the risk of an adverse cardiovascular event (126 ). In patients with endstage renal disease on hemodialysis, increased concentrations of sCD40L strongly and independently predict (relative risk 6.8) nonfatal and fatal atherothrombotic events (127 ).…”

Section: Soluble Cd40 Ligandmentioning

confidence: 99%

Inflammation in Atherosclerosis: From Vascular Biology to Biomarker Discovery and Risk Prediction

Packard

Libby²

2008

Clinical Chemistry

799

588

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Recent investigations of atherosclerosis have focused on inflammation, providing new insight into mechanisms of disease. Inflammatory cytokines involved in vascular inflammation stimulate the generation of endothelial adhesion molecules, proteases, and other mediators, which may enter the circulation in soluble form. These primary cytokines also induce production of the messenger cytokine interleukin-6, which stimulates the liver to increase production of acute-phase reactants such as C-reactive protein. In addition, platelets and adipose tissue can generate inflammatory mediators relevant to atherothrombosis. Despite the irreplaceable utility of plasma lipid profiles in assessment of atherosclerotic risk, these profiles provide an incomplete picture. Indeed, many cardiovascular events occur in individuals with plasma cholesterol concentrations below the National Cholesterol Education Program thresholds of 200 mg/dL for total cholesterol and 130 mg/dL for low-density lipoprotein (LDL) cholesterol. The concept of the involvement of inflammation in atherosclerosis has spurred the discovery and adoption of inflammatory biomarkers for cardiovascular risk prediction. C-reactive protein is currently the best validated inflammatory biomarker; in addition, soluble CD40 ligand, adiponectin, interleukin 18, and matrix metalloproteinase 9 may provide additional information for cardiovascular risk stratification and prediction. This review retraces the biology of atherothrombosis and the evidence supporting the role of inflammatory biomarkers in predicting primary cardiovascular events in this biologic context.

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Section: Soluble Cd40 Ligandmentioning

confidence: 99%

Inflammation in Atherosclerosis: From Vascular Biology to Biomarker Discovery and Risk Prediction

Packard

Libby²

2008

Clinical Chemistry

799

588

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“…Interestingly, in chronic kidney disease circulating CD40 levels are elevated 10, 11 and are associated with impaired immunity, presumably by binding circulating sCD40L and preventing its interaction with tissue bound CD40 11 . Soluble CD40L levels do not appear to be elevated in end-stage renal disease (ESRD) per se, however, the levels are elevated in ESRD patients with coronary artery disease (CAD) or that have atherothrombotic events 12, 13 .…”

Section: Introductionmentioning

confidence: 99%

Effect of CD40 and sCD40L on Renal Function and Survival in Patients With Renal Artery Stenosis

et al. 2013

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Activation of the CD40 receptor on the proximal tubular epithelium of the kidney results in fibrosis and inflammation in experimental models of kidney injury. Soluble CD40 ligand is released by activated platelets. The role of CD40-soluble CD40 ligand in patients with ischemic renal disease is unknown. Plasma levels of CD40 and soluble CD40 ligand were measured by enzyme linked immunosorbent assay in a single center cohort of 60 patients with renal artery stenosis recruited from Salford Royal Hospital, Manchester, UK. A natural log transformation of CD40 and soluble CD40 ligand was performed to normalize the data. Estimated glomerular filtration rate was used as the primary indicator of renal function. By univariate analysis low baseline levels of circulating CD40 (R2=0.06, p<0.05) and baseline creatinine (R2=0.08, p=0.022) were associated with loss of kidney function at one-year follow-up, whereas soluble CD40 ligand was not (R2=0.02, p=ns). In a multiple linear regression model CD40 (p<0.02) and baseline creatinine (p<0.01) continued to be significantly associated with a decline in renal function (model R2=0.17, p<0.005). Baseline CD40 levels were somewhat lower in patients who died during follow-up (survivors, 7.3 ± 0.9 pg/ml, n=48 vs. non-survivors, 6.7 ± 1.0 pg/ml, n=12, p=0.06). The CD40/soluble CD40 ligand signaling cascade may be a novel mechanism contributing to the development and progression of renal injury in patients with atherosclerotic renal artery stenosis.

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“…From the initial cohort of 245 prevalent patients [28][29][30] , 230 plasma probes were available for the current study. These 230 patients on maintenance haemodialysis were followed prospectively for 52 months.…”

Section: Resultsmentioning

confidence: 99%

“…Cut-off values were calculated for the whole study population and for men and women separately. Those cut-off values were used to transform individual continuous parameters into binary endpoints as described before [28] .…”

Section: Discussionmentioning

confidence: 99%

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Gender-Dependent Impact of Risk Factors for Cardiovascular and Non-Cardiovascular Mortality in End-Stage Renal Disease Patients on Haemodialysis

Hocher

Kalk²,

Godes³

et al. 2008

Kidney Blood Press Res

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We investigated whether mortality risk factors are gender dependent in haemodialysis patients. Patients (n = 230; 118 women, 112 men) on haemodialysis were followed for 52 months to assess the incidence of death due to cardiovascular or non-cardiovascular causes. Survival was compared by Cox regression analysis using age, diabetes, pre-existing coronary disease, troponin T and C-reactive protein as covariates. In total, 120 participants (52.2%) died within the 52 months of follow-up: 57 patients died of cardiovascular disease, 35 patients died of infectious diseases. Cox regression revealed that age, pre-existing coronary heart disease and troponin T were independent all-cause mortality risk factors for both sexes. Analyzing men and women separately revealed that diabetes and C-reactive protein seemed to be a stronger risk factors for all-cause mortality in women. Cardiovascular mortality was predicted by troponin T in women (relative risk = 5.16, 95% CI: 1.67–15.88; p = 0.004), but not in men (relative risk = 1.69; 95% CI: 0.72–3.96; p = 0.23). Our study showed for the first time that the impact of risk factors in predicting death due to cardiovascular disease is clearly gender dependent.

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Soluble CD154 Is a Unique Predictor of Nonfatal and Fatal Atherothrombotic Events in Patients Who Have End-Stage Renal Disease and Are on Hemodialysis

Cited by 17 publications

References 38 publications

Inflammation in Atherosclerosis: From Vascular Biology to Biomarker Discovery and Risk Prediction

Inflammation in Atherosclerosis: From Vascular Biology to Biomarker Discovery and Risk Prediction

Effect of CD40 and sCD40L on Renal Function and Survival in Patients With Renal Artery Stenosis

Gender-Dependent Impact of Risk Factors for Cardiovascular and Non-Cardiovascular Mortality in End-Stage Renal Disease Patients on Haemodialysis

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