Background and objectives: Vascular calcification and endothelial dysfunction contribute to the development of cardiovascular disease in patients with chronic kidney disease (CKD). Sevelamer, a non–calcium-based phosphate binder, has been shown to attenuate cardiovascular calcification in CKD patients, although the exact mechanism has not been clarified. This study was designed to investigate the effect of short-term sevelamer treatment on both serum fetuin-A concentrations and endothelial dysfunction seen in CKD patients. Design, setting, participants, & measurements: Fifty nondiabetic stage 4 CKD patients whose phosphate levels were ≥5.5 mg/dl were enrolled in this 8-wk randomized prospective study. Thirty-six healthy volunteers served as matched controls. Patients were treated with either sevelamer (n = 25, 12 males) or calcium acetate (n = 25, 13 males). Fetuin-A, high-sensitivity C-reactive protein, Ca × PO₄ product, flow-mediated dilation (FMD), insulin, and homeostasis model assessment (HOMA) were obtained at baseline and after the treatment period. Results: As expected, CKD patients had significantly lower levels of fetuin-A and FMD, and significantly higher levels of intact parathyroid hormone, Ca × PO₄ product, and high-sensitivity C-reactive protein than controls (P < 0.001 for all). The use of sevelamer led to a significant increase in the fetuin-A concentration with improvement in FMD, whereas no significant difference was observed in the calcium acetate group. In a multiple regression analysis, FMD levels were independently related to fetuin-A both before (β = 0.63, P < 0.001) and after (β = 0.38, P = 0.004) treatment. Conclusions: This small, randomized, prospective study shows that short-term sevelamer treatment significantly increases fetuin-A levels and improves FMD in nondiabetic stage 4 CKD patients.

Background . Endothelial dysfunction (ED) is common in patients with moderate to advanced chronic kidney disease (CKD). Recently, visfatin, a protein with insulin-mimetic properties, was shown to be associated with sVCAM-1. Thus, we hypothesised that visfatin may be a marker of ED in CKD. Methods . We studied 406 patients with different stages of non-diabetic CKD (50% males, 46 ± 12 years), testing the relationship between flow-mediated dilatation (FMD), assessed by high resolution brachial ultrasonography, and plasma adiponectin and visfatin concentrations. Eighty healthy volunteers (50% males, 46 ± 11 years) served as matched controls. Results . Compared to healthy controls, ED was observed in all stages of CKD (Stages 1–5) and correlated strongly with the reduction in estimated glomerular filtration rate (eGFR). Whereas visfatin concentrations were found to be increased in all but CKD stages 1 and 2, adiponectin levels were found to be increased in all patients but CKD stage 1. Visfatin and adiponectin levels were strongly correlated with eGFR (rho = −0.62 and rho = −0.72, respectively, P < 0.001 for both). FMD levels were negatively correlated with both visfatin and adiponectin levels (rho = −0.53 and, rho = −0.57, respectively, P < 0.001 for both). In a multiple regression model, eGFR levels (Beta = 0.74, P < 0.001), visfatin (Beta = −0.15, P < 0.001), age (Beta = 0.06, P < 0.01), adiponectin (Beta = 0.09, P < 0.05), HOMA-IR (Beta = 0.07, P < 0.05) and hsCRP (Beta = −0.08, P < 0.05) were all found to be significantly related to FMD. Conclusions . We conclude that the circulating levels of visfatin and adiponectin are associated with ED in all stages of CKD, independently of inflammation and insulin resistance.