Document Detail


Association of low fetuin-A (AHSG) concentrations in serum with cardiovascular mortality in patients on dialysis: a cross-sectional study.
MedLine Citation:
PMID:  12642050     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: Vascular calcification is the most prominent underlying pathological finding in patients with uraemia, and is a predictor of mortality in this population. Fetuin-A (alpha2-Heremans Schmid glycoprotein; AHSG) is an important circulating inhibitor of calcification in vivo, and is downregulated during the acute-phase response. We aimed to investigate the hypothesis that AHSG deficiency is directly related to uraemic vascular calcification. METHODS: We did a cross-sectional study in 312 stable patients on haemodialysis to analyse the inter-relation of AHSG and C-reactive protein (CRP) and their predictive effect on all-cause and cardiovascular mortality, over a period of 32 months. Subsequently, we tested the capacity of serum to inhibit CaxPO4 precipitation in patients on long-term dialysis (n=17) with apparent soft-tissue calcifications, and in those on short-term dialysis (n=8) without evidence of calcifications and cardiovascular disease. FINDINGS: AHSG concentrations in serum were significantly lower in patients on haemodialysis (mean 0.66 g/L [SD 0.28]) than in healthy controls (0.72 [0.19]). Low concentrations of the glycoprotein were associated with raised amounts of CRP and with enhanced cardiovascular (p=0.031) and all-cause mortality (p=0.0013). Sera from patients on long-term dialysis with low AHSG concentrations showed impaired ex-vivo capacity to inhibit CaxPO4 precipitation (mean IC50: 9.0 microL serum [SD 3.1] vs 7.5 [0.8] in short-term patients and 6.4 [2.6] in controls). Reconstitution of sera with purified AHSG returned this impairment to normal. Interpretation AHSG deficiency is associated with inflammation and links vascular calcification to mortality in patients on dialysis. Activated acute-phase response and AHSG deficiency might account for accelerated atherosclerosis in uraemia.
Authors:
Markus Ketteler; Philipp Bongartz; Ralf Westenfeld; Joachim Ernst Wildberger; Andreas Horst Mahnken; Roland Böhm; Thomas Metzger; Christoph Wanner; Willi Jahnen-Dechent; Jürgen Floege
Publication Detail:
Type:  Journal Article; Multicenter Study; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Lancet     Volume:  361     ISSN:  0140-6736     ISO Abbreviation:  Lancet     Publication Date:  2003 Mar 
Date Detail:
Created Date:  2003-03-18     Completed Date:  2003-04-04     Revised Date:  2009-11-03    
Medline Journal Info:
Nlm Unique ID:  2985213R     Medline TA:  Lancet     Country:  England    
Other Details:
Languages:  eng     Pagination:  827-33     Citation Subset:  AIM; IM    
Affiliation:
Department of Nephrology and Immunology, University Hospital Aachen, Aachen, Germany. mketteler@ukaachen.de
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MeSH Terms
Descriptor/Qualifier:
Blood Proteins / deficiency*,  metabolism
Calcinosis / etiology
Cardiovascular Diseases / blood,  mortality*
Case-Control Studies
Cross-Sectional Studies
Female
Germany
Humans
Male
Middle Aged
Renal Dialysis*
Chemical
Reg. No./Substance:
0/Blood Proteins; 0/alpha2HS glycoprotein

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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