Associations of serum fetuin-A with malnutrition, inflammation, atherosclerosis and valvular calcification syndrome and outcome in peritoneal dialysis patients.
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.
Wang
Angela Yee-Moon
AY
Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, New Territories, Hong Kong. awang@cuhk.edu.hk
Woo
Jean
J
Lam
Christopher Wai-Kei
CW
Wang
Mei
M
Chan
Iris Hiu-Shuen
IH
Gao
Ping
P
Lui
Siu-Fai
SF
Li
Philip Kam-Tao
PK
Sanderson
John E
JE
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
C556354:AHSG protein, human; D001798:Blood Proteins; D012709:Serum Albumin; D060749:alpha-2-HS-Glycoprotein; D002097:C-Reactive Protein