Title:
Association of serum fetuin-A (AHSG) concentrations with arterial stiffness in patients on dialysis

MMH Hermans¹ ;MMH Hermans² ;MMH Hermans² ;MMH Hermans¹ ;MMH Hermans¹ ;MMH Hermans³ ;MMH Hermans⁴ ;MMH Hermans⁴ ;MMH Hermans⁵ ;MMH Hermans⁶ ;MMH Hermans² ;MMH Hermans¹

Maastricht Aachen Germany' ne '' ; 4. Department of Internal Medicine and Nephrology Elisabeth Hospital Tilburg ; 5. Department of Internal Medicine and Nephrology Catharina Hospital Eindhoven Maastricht

E-mail address corresponding author:
mherm@sint.azm.nl

Background:
An increase in arterial stiffness, as reflected by an increase in pulse wave velocity (PWV) or aortic augmentation index (AI) is an important predictor of cardiovascular mortality in dialysis patients. In addition to age, diabetes mellitus and disorders of calcium (Ca) and phosphate (P) metabolism, respectively, dysregulation of calcification inhibitors such as fetuin-A (α2-Heremans-Schmid-Glycoprotein; AHSG) is potentially involved in vascular pathology in dialysis patients. AHSG was recently found to be inversely related to mortality in dialysis patients. In this study, the relation between AHSG serum concentration and PWV and AI was investigated in dialysis patients.

Methods:
In a cross-sectional study we included 109 dialysis patients (28 peritoneal dialysis (PD), 81 haemodialysis (HD)), and 31 controls. Time-averaged values of serum albumin, Ca, P, and iPTH were included in multiregression analysis, as were high-sensitivity C-reactive protein (hsCRP), AHSG, age and mean arterial pressure (MAP) and dialysis modality. PWV and AI were measured by tonometry, (SphygmoCor). Brachial blood pressure was measured by oscillometry (Collin).

Results:
Mean AHSG concentration in dialysis patients (0.63±0.16 g/l) did not differ from controls (0.62±0.11 g/l). PWV was significantly higher in dialysis patients (9.9±2.97 m/s) compared to controls (7.9±1.5 m/s) (p<0.001). In univariate analysis in dialysis patients, AHSG levels were inversely and significantly related to both PWV (r=-0.256, p=0.007) and AI (r=-0.284, p=0.003). Analyzing patients with a hsCRP > 10mg/l the significance of the correlation between AHSG and PWV (r=-0.547, p=0.007) and AI (r=-0.615, p=0.002) further increased. In multivariate analysis age, MAP and diabetes mellitus however were the strongest predictors of PWV and AI. AHSG was significantly higher in PD compared to HD patients.

Conclusion:
In summary, in a cohort of dialysis patients serum AHSG levels were inversed related to arterial stiffness as measured with PWV and AI. In patients with elevated CRP levels the correlation was stronger. However, AHSG deficiency could not be identified as an independent predictor of vascular stiffness after adjustment for age, diabetes mellitus and MAP.

Subject:
Hemodialysis

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