title: Associations of serum fetuin-A with malnutrition, inflammation, atherosclerosis and valvular calcification syndrome and outcome in peritoneal dialysis patients.
abstract: BACKGROUND
  Fetuin-A (alpha2-Heremans Schmid glycoprotein) has recently been identified as a circulating inhibitor of calcification and is regulated as a negative acute phase protein. However, its relationships with cardiac valvular calcification and atherosclerosis and outcome have not been evaluated in peritoneal dialysis (PD) patients.
  
  
  METHODS
  We performed a prospective follow-up study in 238 PD patients with echocardiography done at baseline to detect cardiac valvular calcification and biochemical analysis performed for serum fetuin-A, albumin and C-reactive protein (CRP).
  
  
  RESULTS
  Baseline serum fetuin-A concentration was (mean+/-SD) 0.309+/-0.068 g/l (normal range 0.4-0.95). Across the three tertiles of increasing serum fetuin-A, a significant trend effect was observed for age (P = 0.023), diabetes (P = 0.008), background atherosclerotic vascular disease (P = 0.010), cardiac valvular calcification (P = 0.002), serum albumin (P<0.001), subjective global assessment (P = 0.005) and CRP (P<0.001). Adjusting for CRP and calcium x phosphorus product, every 0.01 g/l increase in serum fetuin-A remained independently associated with a 6% decrease in the risk of valvular calcification (95% confidence intervals, 0.90-0.99; P = 0.028). Furthermore, serum fetuin-A showed a significant decrease across the four groups of patients with increasing components of the malnutrition, inflammation, atherosclerosis/calcification (MIAC) syndrome (P<0.001) and was the lowest among patients with all components of the MIAC syndrome (0.263+/-0.055 g/l) and highest among those who do not have the MIAC syndrome at all (0.338+/-0.063 g/l). Lower serum fetuin-A was associated with greater all-cause mortality (P = 0.0011) and fatal and non-fatal cardiovascular events (P = 0.0017), but its significance was lost when atherosclerotic vascular disease, valvular calcification, inflammation and malnutrition were included in the model.
  
  
  CONCLUSIONS
  Serum fetuin-A showed important associations with valvular calcification, atherosclerosis, malnutrition and inflammation, and was linked to mortality and cardiovascular events in PD patients via its close relationships with the MIAC syndrome.
authors.affiliation: Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, New Territories, Hong Kong. awang@cuhk.edu.hk
authors.forename: Angela Yee-Moon
authors.initials: AY
authors.lastname: Wang
authors.forename: Jean
authors.initials: J
authors.lastname: Woo
authors.forename: Christopher Wai-Kei
authors.initials: CW
authors.lastname: Lam
authors.forename: Mei
authors.initials: M
authors.lastname: Wang
authors.forename: Iris Hiu-Shuen
authors.initials: IH
authors.lastname: Chan
authors.forename: Ping
authors.initials: P
authors.lastname: Gao
authors.forename: Siu-Fai
authors.initials: SF
authors.lastname: Lui
authors.forename: Philip Kam-Tao
authors.initials: PK
authors.lastname: Li
authors.forename: John E
authors.initials: JE
authors.lastname: Sanderson
mesh_terms: D001161:Arteriosclerosis / Q000097:blood* / Q000209:etiology; D001798:Blood Proteins / Q000378:metabolism*; D002097:C-Reactive Protein / Q000378:metabolism; D002114:Calcinosis / Q000097:blood / Q000209:etiology; D004452:Echocardiography; D005260:Female; D005500:Follow-Up Studies; D006349:Heart Valve Diseases / Q000097:blood* / Q000209:etiology; D006801:Humans; D007249:Inflammation / Q000097:blood* / Q000209:etiology; D007676:Kidney Failure, Chronic / Q000628:therapy*; D008297:Male; D044342:Malnutrition / Q000097:blood*; D008875:Middle Aged; D010530:Peritoneal Dialysis; D011446:Prospective Studies; D012709:Serum Albumin / Q000378:metabolism; D015996:Survival Rate; D013577:Syndrome; D060749:alpha-2-HS-Glycoprotein
chemical_list: C556354:AHSG protein, human; D001798:Blood Proteins; D012709:Serum Albumin; D060749:alpha-2-HS-Glycoprotein; D002097:C-Reactive Protein