Vascular access calcification predicts mortality in hemodialysis patients

Schlieper, Georg; Krüger, Thilo; Djurić, Živka; Damjanović, Tatjana; Marković, Nataša; Schurgers, Leon J.; Brandenburg, Vincent; Westenfeld, Ralf; Dimković, Siniša; Ketteler, Markus; Grootendorst, Diana C.; Dekker, Friedo W.; Floege, Jürgen; Dimković, Nada

doi:10.1038/ki.2008.458

Cited by 80 publications

(65 citation statements)

References 19 publications

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“…Valvular calcifications were determined by one single observer using echocardiography with an Aspen-ACUSON device (Mountain View, CA) equipped with a 2.5-MHz probe and calcified carotid plaques were defined as echogenic structures showing protrusion into the lumen with focal widening that was 50% greater than the intima media thickness (IMT) of adjacent sites. 27 In addition to single calcification sites, we calculated two semiquantitative calcification scores. 12 First, we determined the Adragao score by analyzing conventional x-rays of the pelvis and hands.…”

Section: Mgp Species Studies Interpretationmentioning

confidence: 99%

“…It has been shown for the Adragao score that patients with a score of 0 to 2 have a better prognosis than those with a score of 3 to 8. 11,12 Moreover, the presence of calcifications of the heart valves 28 and the AV fistula 27 have been shown to be a mortality risk factor. Bellasi et al 29 reported that simple measures of cardiovascular calcification had a very good correlation with more sophisticated measurements obtained with CT.…”

Section: Mgp Species Studies Interpretationmentioning

confidence: 99%

“…27 Briefly, pulse wave velocity was assessed using one carotid and one femoral sensor simultaneously to determine the velocity of the pulse in relation to the distance between the femoral artery and the suprasternal notch (Complior SP system; Artech Medical, Pantin, France). Two measurements were performed by two trained observers.…”

Section: Assessment Of Cardiovascular Parametersmentioning

confidence: 99%

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Circulating Nonphosphorylated Carboxylated Matrix Gla Protein Predicts Survival in ESRD

Schlieper¹,

Westenfeld²,

Krüger³

et al. 2011

Journal of the American Society of Nephrology

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213

181

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The mechanisms for vascular calcification and its associated cardiovascular mortality in patients with ESRD are not completely understood. Dialysis patients exhibit profound vitamin K deficiency, which may impair carboxylation of the calcification inhibitor matrix gla protein (MGP). Here, we tested whether distinct circulating inactive vitamin K-dependent proteins associate with all-cause or cardiovascular mortality. We observed higher levels of both desphospho-uncarboxylated MGP (dp-ucMGP) and desphospho-carboxylated MGP (dp-cMGP) among 188 hemodialysis patients compared with 98 agematched subjects with normal renal function. Levels of dp-ucMGP correlated with those of protein induced by vitamin K absence II (PIVKA-II; r ϭ 0.62, P Ͻ 0.0001). We found increased PIVKA-II levels in 121 (64%) dialysis patients, indicating pronounced vitamin K deficiency. Kaplan-Meier analysis showed that patients with low levels of dp-cMGP had an increased risk for all-cause and cardiovascular mortality. Multivariable Cox regression confirmed that low levels of dp-cMGP increase mortality risk (all-cause: HR, 2.2; 95% CI, 1.1 to 4.3; cardiovascular: HR, 2.7; 95% CI, 1.2 to 6.2). Furthermore, patients with higher vascular calcification scores showed lower levels of dp-cMGP. In 17 hemodialysis patients, daily supplementation with vitamin K2 for 6 weeks reduced dp-ucMGP levels by 27% (P ϭ 0.003) but did not affect dp-cMGP levels. In conclusion, the majority of dialysis patients exhibit pronounced vitamin K deficiency. Lower levels of circulating dp-cMGP may serve as a predictor of mortality in dialysis patients. Whether vitamin K supplementation improves outcomes requires further study. 22: 387-395, 201122: 387-395, . doi: 10.1681 Dialysis patients show an increased total and cardiovascular mortality. 1 Cardiovascular calcifications are well-established mortality predictors in ESRD patients. 2 Calcification is not only a passive but an actively regulated process dependent on calcification inhibitors. 3 Fetuin-A, a liver-derived protein, acts as a systemic calcification inhibitor, 4 and low serum levels have been shown to predict mortality in dialysis patients. 5 Matrix gla protein (MGP) is produced by vascular smooth muscle cells and acts locally in the vascular wall. 6 MGP can be modified by ␥-glutamate carboxylation and serine phosphorylation. The function of phosphorylation is not yet known, but recent data suggest that it plays a role in regulating the secretion of proteins into the extracellular environ- J Am Soc Nephrol

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Section: Mgp Species Studies Interpretationmentioning

confidence: 99%

Section: Mgp Species Studies Interpretationmentioning

confidence: 99%

Section: Assessment Of Cardiovascular Parametersmentioning

confidence: 99%

See 1 more Smart Citation

Circulating Nonphosphorylated Carboxylated Matrix Gla Protein Predicts Survival in ESRD

Schlieper¹,

Westenfeld²,

Krüger³

et al. 2011

Journal of the American Society of Nephrology

Self Cite

213

181

View full text Add to dashboard Cite

show abstract

“…Increased vascular calcification is a major cause of increased morbidity and mortality in dialysis patients (36,37). Vascular calcification is an active cell-mediated process and likely reflects a transformation of vascular smooth muscle cells to osteoblast-like cells.…”

Section: Inflammation As a Catalyst Of The Vascular Calcification Promentioning

confidence: 99%

Persistent Inflammation as a Catalyst for Other Risk Factors in Chronic Kidney Disease

Carrero¹,

Stenvinkel²

2009

Clinical Journal of the American Society of Nephrology

182

131

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Because inflammation by now is a "traditional" finding that predicts poor outcome and cardiovascular events in the vast majority of patients with ESRD, it could be argued that inflammatory biomarkers should not longer be considered "novel" risk factors. In this review, we forward the hypothesis that, in addition to putative direct proatherogenic effects, persistent inflammation may serve as a catalyst and, in the toxic uremic milieu, modulate the effects of other concurrent vascular and nutritional risk factors. We discuss some recent observational studies, suggesting that the presence of persistent inflammation magnifies the risk for poor outcome via mechanisms related to self-enhancement of the inflammatory cascade and exacerbation of both the wasting and the vascular calcification processes. Because persistent inflammation may be the silent culprit of other commonly observed pathophysiologic alterations in chronic kidney disease, it is imperative that inflammatory markers be regularly monitored and therapeutic attempts be made to target persistent low-grade inflammation in this patient group.

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“…Similarly, in hemodialysis patients OPG levels were found to be strongly associated with aortic or carotid-to-femoral PWV independently of traditional and uremia-related risk factors including markers of inflammation [25,26,30] . However, other studies in adults and children on hemodialysis treatment were unable to confirm the above findings [19,31] .…”

Section: Opg and Vascular Calcifications In Ckd Patientsmentioning

confidence: 81%

Receptor activator of nuclear factor κB ligand/osteoprotegerin axis and vascular calcifications in patients with chronic kidney disease

Spartalis

Papagianni

2016

WJN

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Vascular calcifications are commonly observed in patients with chronic kidney disease (CKD) and contribute to the excessive cardiovascular morbidity and mortality rates observed in these patients populations. Although the pathogenetic mechanisms are not yet fully elucidated, recent evidence suggests a link between bone metabolism and the development and progression of vascular calcifications. Moreover, accumulating data indicate that receptor activator of nuclear factor κB ligand/osteoprotegerin axis which plays essential roles in the regulation of bone metabolism is also involved in extra-osseous bone formation. Further studies are required to establish the prognostic significance of the above biomarkers as predictors of the presence and severity of vascular calcifications in CKD patients and of cardiovascular morbidity and mortality. Moreover, randomized clinical trials are needed to clarify whether inhibition of osteoclast activity will protect from vascular calcifications. Core tip: Vascular calcifications are commonly observed in chronic kidney disease patients and recently mounting evidence suggest that Receptor activator of nuclear factor κB ligand/osteoprotegerin axis controls both bone metabolism and extra-osseous bone formation. Further studies are required to establish the role of these biomarkers as predictors of the presence and severity of vascular calcifications and of cardiovascular morbidity and mortality. Moreover, randomized clinical trials are needed to clarify whether inhibition of osteoclast activity will protect from vascular calcifications.Spartalis M, Papagianni A. Receptor activator of nuclear factor κB ligand/osteoprotegerin axis and vascular calcifications in patients EDITORIAL 1 January 6, 2016|Volume 5|Issue 1|

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Vascular access calcification predicts mortality in hemodialysis patients

Cited by 80 publications

References 19 publications

Circulating Nonphosphorylated Carboxylated Matrix Gla Protein Predicts Survival in ESRD

Circulating Nonphosphorylated Carboxylated Matrix Gla Protein Predicts Survival in ESRD

Persistent Inflammation as a Catalyst for Other Risk Factors in Chronic Kidney Disease

Receptor activator of nuclear factor κB ligand/osteoprotegerin axis and vascular calcifications in patients with chronic kidney disease

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