Fetuin-A is not associated with mortality in chronic kidney disease

Ix, Joachim H.; Shlipak, Michael G.; Sarnak, Mark J.; Beck, Gerald J.; Greene, Tom; Wang, X.; Kusek, John W.; Collins, Allan J.; Levey, Andrew S.; Menon, Vandana

doi:10.1038/sj.ki.5002549

Cited by 33 publications

(27 citation statements)

References 39 publications

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Section: Discussionmentioning

confidence: 54%

“…In addition, data from a recent study including a larger number of patients with less severe impairment of renal function do not support the conclusion that low fetuin-A levels are associated with increased all-cause or cardiovascular mortality. 35 Notably, adjustment for creatinine levels (that were essentially in the normal range in this study) did not influence the association between fetuin-A and risk of CVD.Because circulating fetuin-A is a well-described inhibitor of calcification, 33,36 increased vascular calcification in patients with renal disease who display low fetuin-A levels is likely to be the mechanism for increased mortality. Two additional studies mainly or exclusively performed in coronary heart disease *RRs were adjusted for sex, smoking status, BMI, waist circumference, alcohol intake, education, sports, prevalent hypertension, prevalent diabetes mellitus, total cholesterol, HDL cholesterol, and log transformed hs-CRP.…”

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confidence: 59%

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Plasma Fetuin-A Levels and the Risk of Myocardial Infarction and Ischemic Stroke

et al. 2008

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Background-Fetuin-A, a protein almost exclusively secreted by the liver, induces insulin resistance and subclinical inflammation in rodents. Circulating fetuin-A levels are elevated in humans with metabolic syndrome and insulin resistance, conditions that are associated with increased risk of cardiovascular disease. Methods and Results-We investigated the association between fetuin-A levels and the risk of future myocardial infarction (MI) and ischemic stroke (IS) in a case-cohort study based on the European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam Study comprising 27 548 middle-aged subjects of the general population. Fetuin-A levels were measured in plasma of 227 individuals who developed MI, in 168 who developed IS, and in 2198 individuals who remained free of cardiovascular events during a mean follow-up of 8.2Ϯ2.2 years. Individuals in the highest compared with the lowest quintile of plasma fetuin-A had significantly increased risks of MI (relative risk, 3.80; 95% confidence interval, 2.37 to 6.10; P for trend Ͻ0.0001) and IS (relative risk, 3.93; 95% confidence interval, 2.17 to 7.12; P for trend Ͻ0.0001) after adjustment for sex and age. Additional adjustment for smoking status, body mass index, waist circumference, alcohol consumption, educational attainment, physical activity, hypertension, diabetes mellitus, total and high-density lipoprotein cholesterol, and C-reactive protein only moderately attenuated these risks (MI: relative risk, 3.25; 95% confidence interval, 2.01 to 5.28; P for trend Ͻ0.0001; IS: relative risk, 3.78; 95% confidence interval, 2.06 to 6.94; P for trend Ͻ0.0001). Conclusions-Our data provide evidence for a link between high plasma fetuin-A levels and an increased risk of MI and IS.Therefore, more research is warranted to determine the role of fetuin-A in the pathophysiology of cardiovascular disease. Key Words: atherosclerosis Ⅲ cerebral infarction Ⅲ coronary disease Ⅲ risk factors I nsulin resistance, abdominal obesity, and other components of the metabolic syndrome are established risk factors of cardiovascular diseases (CVD). 1 Recent evidence suggests that nonalcoholic fatty liver disease adds independently of established cardiovascular risk factors to risk of atherosclerosis and CVD. 2 Nonalcoholic fatty liver disease is present in the majority of patients with the metabolic syndrome, and it is increasingly common in the general population. 3 The severity of nonalcoholic fatty liver disease is related to the extent of atherosclerosis. 4 -6 Clinical Perspective p 2562Fatty liver status contributes to dyslipidemia, hyperglycemia, and subclinical inflammation, 2 all known as risk factors of CVD, 7,8 and may induce production and secretion of other factors involved in the pathophysiology of atherosclerosis.Such a candidate is the glycoprotein fetuin-A, also referred to as ␣ 2 -Heremans-Schmid glycoprotein, which is almost exclusively expressed and secreted by the liver, particularly under hepatic steatosis. 9 Fetuin-A is a natural inhibitor of the in...

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Section: Discussionmentioning

confidence: 54%

mentioning

confidence: 59%

Plasma Fetuin-A Levels and the Risk of Myocardial Infarction and Ischemic Stroke

et al. 2008

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“…It is plausible that inflammation and fetuin-A are factors in a shared pathophysiologic pathway, whereby chronic inflammation contributes to deficiency of fetuin-A, promoting dystrophic calcification and higher mortality risk (46). Lower fetuin-A levels have not been consistently associated with mortality or cardiovascular disease in populations not undergoing dialysis (16,(48)(49)(50)(51). In this study, we observed a threshold effect whereby only levels ,0.5 g/L were associated with increasing mortality, which may account for apparently conflicting results.…”

Section: Discussionmentioning

confidence: 99%

Biomarkers of Vascular Calcification and Mortality in Patients with ESRD

Scialla

Kao

Crainiceanu

et al. 2014

Clinical Journal of the American Society of Nephrology

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Background Vascular calcification is common among patients undergoing dialysis and is associated with mortality. Factors such as osteoprotegerin (OPG), osteopontin (OPN), bone morphogenic protein-7 (BMP-7), and fetuin-A are involved in vascular calcification.Design, setting, participants, & measurements OPG, OPN, BMP-7, and fetuin-A were measured in blood samples from 602 incident dialysis patients recruited from United States dialysis centers between 1995 and 1998 as part of the Choices for Healthy Outcomes In Caring for ESRD Study. Their association with all-cause and cardiovascular mortality were assessed using Cox proportional hazards models adjusted for demographic characteristics, comorbidity, serum phosphate, and calcium. An interaction with diabetes was tested because of its known association with vascular calcification. Predictive accuracy of selected biomarkers was explored by C-statistics in nested models with training and validation subcohorts.Results Higher OPG and lower fetuin-A levels were associated with higher mortality over up to 13 years of follow-up (median, 3.4 years). The adjusted hazard ratios (HR) for highest versus lowest tertile were 1.49 (95% confidence interval [95% CI], 1.08 to 2.06) for OPG and 0.69 (95% CI, 0.52 to 0.92) for fetuin-A. In stratified models, the highest tertile of OPG was associated with higher mortality among patients without diabetes (HR, 2.42; 95% CI, 1.35 to 4.34), but not patients with diabetes (HR, 1.26; 95% CI, 0.82 to 1.93; P for interaction=0.001). In terms of cardiovascular mortality, higher fetuin-A was associated with lower risk (HR, 0.85 per 0.1 g/L: 95% CI, 0.75 to 0.96). In patients without diabetes, higher OPG was associated with greater risk (HR for highest versus lowest tertile, 2.91; 95% CI, 1.06 to 7.99), but not in patients with diabetes or overall. OPN and BMP-7 were not independently associated with outcomes overall. The addition of OPG and fetuin-A did not significantly improve predictive accuracy of mortality.Conclusions OPG and fetuin-A may be risk factors for all-cause and cardiovascular mortality in patients undergoing dialysis, but do not improve risk prediction.

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“…Decreased serum levels of fetuin-A have been associated with a worse cardiovascular calcification status (22,23). In HD patients, lower fetuin-A serum levels correlated with increased mortality in some (24 -26) but not all (27) studies. In a trial of patients with stage 4 CKD and without diabetes, significantly increased concentrations of serum fetuin-A were noted after short-term treatment with sevelamer but not with calcium acetate (28).…”

Section: Effects Of Phosphate Binders On Biomarkersmentioning

confidence: 99%

Ten-Year Experience with Sevelamer and Calcium Salts as Phosphate Binders

Raggi

Vukičević

Moysés

et al. 2010

Clinical Journal of the American Society of Nephrology

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Most patients with chronic kidney disease experience abnormalities in serum calcium, phosphorus, parathyroid hormone, and vitamin D metabolism. These can lead to vascular calcification (VC), which has been associated with increased risk for cardiovascular disease and mortality. Although hyperphosphatemia is believed to be a risk factor for mortality and VC, no randomized trial was ever designed to demonstrate that lowering phosphate reduces mortality. Nonetheless, binders have been used extensively, and the preponderance of evidence shows that sevelamer slows the development of VC whereas calcium salts do not. Four studies have demonstrated a slower progression of VC with sevelamer than with calcium-containing binders, although a fifth study showed nonsuperiority. Conversely, the results on mortality with sevelamer have been variable, and data on calcium-based binders are nonexistent. Improved survival with sevelamer was demonstrated in a small randomized clinical trial, whereas a larger randomized trial failed to show a benefit. In addition, preclinical models of renal failure and preliminary clinical data on hemodialysis patients suggest a potential benefit for bone with sevelamer. Meanwhile, several randomized and observational studies suggested no improvement in bone density and fracture rate, and a few noted an increase in total and cardiovascular mortality in the general population given calcium supplements. Although additional studies are needed, there are at least indications that sevelamer may improve vascular and bone health and, perhaps, mortality in hemodialysis patients, whereas data on calcium-based binders are lacking.

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Fetuin-A is not associated with mortality in chronic kidney disease

Cited by 33 publications

References 39 publications

Plasma Fetuin-A Levels and the Risk of Myocardial Infarction and Ischemic Stroke

Plasma Fetuin-A Levels and the Risk of Myocardial Infarction and Ischemic Stroke

Biomarkers of Vascular Calcification and Mortality in Patients with ESRD

Ten-Year Experience with Sevelamer and Calcium Salts as Phosphate Binders

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