Serum fetuin-A in nondialyzed patients with diabetic nephropathy: Relationship with coronary artery calcification

Mehrotra, Rajnish; Westenfeld, Ralf; Christenson, Peter; Budoff, Matthew J.; Ipp, Eli; Takasu, Junichiro; Gupta, Ajay; Norris, Keith C.; Ketteler, Markus; Adler, Sharon G.

doi:10.1111/j.1523-1755.2005.00172.x

Cited by 144 publications

(128 citation statements)

References 43 publications

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“…The positive correlation between circulating fetuin-A and cholesterol levels in this cohort was also observed in a cohort of 222 prevalent hemodialysis patients (32) and supports the link between fetuin-A and dyslipidemia (33,34). Possible factors accounting for this correlation include regular physical activity, which participates in the maintenance of low levels of circulating fetuin-A together with lower plasma cholesterol and enhanced insulin sensitivity (35), nutritional status (25), weight control, and amount of liver fat (36,37). The negative correlation between fetuin-A levels and history of smoking, which has not been reported before, may reflect the consequences of tobacco smoking on liver function, physical activity, and/or weight loss (38).…”

Section: Discussionmentioning

confidence: 93%

Serum Fetuin-A Levels Are Associated with Vascular Calcifications and Predict Cardiovascular Events in Renal Transplant Recipients

Maréchal

Schlieper

Nguyen

et al. 2011

Clinical Journal of the American Society of Nephrology

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SummaryBackground and objectives Vascular calcifications predict cardiovascular disease, the major cause of death in renal transplant recipients (RTRs). We studied the determinants of fetuin-A, a potent circulating calcification inhibitor encoded by the AHSG gene, and tested its association with vascular calcifications and longterm survival and cardiovascular events (CVEs) in RTRs.Design, setting, participants, & measurements Two hundred seventy-seven prevalent RTRs from a single center were included. CVEs and deaths were prospectively recorded during a 5-year follow-up.Results Independent determinants of lower serum fetuin-A levels were lower plasma cholesterol, the AHSG rs4918 G allele, and history of smoking. Low serum fetuin-A level was a determinant of aortic calcifications (assessed using spiral CT). Low fetuin-A levels (Յ0.47 g/L, first quintile) were independently associated with CVEs and deaths (hazard ratio ϭ 1.83; 95% confidence interval, 1.07 to 3.04). The association was confirmed for all-cause mortality, and the major adverse cardiovascular endpoints were analyzed separately. Patients with low fetuin-A and high high-sensitivity C-reactive protein (Ͼ4.36 mg/L, fourth quintile) levels had a 3.5-fold increased risk of all-cause mortality and CVEs. In the presence of inflammation, CVE-free survival was influenced by common variants in the AHSG gene.Conclusions These data show that low fetuin-A levels are independently associated with aortic calcifications and a higher risk of CVEs and mortality. They support fetuin-A as a circulating biomarker able to identify RTRs at risk for vascular calcifications and CVEs.

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Section: Discussionmentioning

confidence: 93%

Serum Fetuin-A Levels Are Associated with Vascular Calcifications and Predict Cardiovascular Events in Renal Transplant Recipients

Maréchal

Schlieper

Nguyen

et al. 2011

Clinical Journal of the American Society of Nephrology

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“…Patients on peritoneal dialysis with low fetuin-A levels showed a clear association with the MIA syndrome as well as with mortality and cardiovascular events [84] . Both coronary and aortic calcifications were found to be related to low fetuin-A levels and in patients with diabetic nephropathy, a positive association between fetuin-A levels and coronary calcification score was demonstrated [85][86][87] . The theory, that fetuin-A up-regulation may serve as a systemic defense mechanism to counteract early VCs, is supported by a study, where immunhistochemistry showed fetuin-A depositions around areas of VC, correlating well with the degree of calcification [85] .…”

Section: Fetuin-amentioning

confidence: 99%

Arterial stiffness, vascular calcification and bone metabolism in chronic kidney disease

Nemcsik

Kiss²,

Tislér³

2012

WJN

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Patients with chronic kidney disease (CKD) have an extremely poor cardiovascular outcome. Arterial stiffness, a strong independent predictor of survival in CKD, is connected to arterial media calcification. A huge number of different factors contribute to the increased arterial calcification and stiffening in CKD, a process which is in parallel with impaired bone metabolism. This coincidence was demonstrated to be part of the direct inhibition of calcification in the vessels, which is a counterbalancing effect but also leads to low bone turnover. Due to the growing evidence, the definition of "CKD mineral bone disorder" was created recently, underlining the strong connection of the two phenomena. In this review, we aim to demonstrate the mechanisms leading to increased arterial stiffness and the up-to date data of the bone-vascular axis in CKD. We overview a list of the different factors, including inhibitors of bone metabolism like osteoprotegerin, fetuin-A, pyrophosphates, matrix Gla protein, osteopontin, fibroblast growth factor 23 and bone morphogenic protein, which seem to play role in the progression of vascular calcification and we evaluate their connection to impaired arterial stiffness in the mirror of recent scientific results.

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“…It is emphasized that an elevated serum fetuin-A level is a sensitive marker of macrovascular complications in diabetics such as coronary atherosclerosis 3,7 . Moreover, Mehrotra et al observed higher serum concentration of fetuin-A among patients with advanced diabetic nephropathy (stages III and IV based on GFR) than in diabetics without kidney disease 41 . Lorant et al found that serum fetuin-A levels were higher in patients without renal disease and with type 2 diabetes and peripheral arterial disease (PAD) than those in individuals with type 2 diabetes and without PAD (ref.…”

Section: The Link Between Fetuin-a and Type 2 Diabetes Mellitusmentioning

confidence: 99%

“…Singh et al suggested that the high concentrations of fetuin-A have been linked to cardiovascular complications in the non-renal patients 7 . In turn, Zhao et al reported that serum fetuin-A levels were independently associated with the presence and severity of coronary artery disease in participants with type 2 diabetes and Mehrotra et al described that fetuin-A concentrations were positively correlated with coronary artery calcifications in nondialized subjects with diabetic nephropathy 41,48 . On the other hand, some clinical studies have indicated the opposite trends-a decrease in fetuin-A levels have been associated with the presence of PAD in diabetics, an increased arterial stiffness, atherosclerotic plaque calcification and progression of cardiovascular disease 14,48 .…”

Section: Fetuin-a As a Marker Of Cardiovascular Diseasementioning

confidence: 99%

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Fetuin-A (AHSG) and its usefulness in clinical practice. Review of the literature

et al. 2015

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Serum fetuin-A in nondialyzed patients with diabetic nephropathy: Relationship with coronary artery calcification

Cited by 144 publications

References 43 publications

Serum Fetuin-A Levels Are Associated with Vascular Calcifications and Predict Cardiovascular Events in Renal Transplant Recipients

Serum Fetuin-A Levels Are Associated with Vascular Calcifications and Predict Cardiovascular Events in Renal Transplant Recipients

Arterial stiffness, vascular calcification and bone metabolism in chronic kidney disease

Fetuin-A (AHSG) and its usefulness in clinical practice. Review of the literature

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