Short-term treatment with sevelamer increases serum fetuin-a concentration and improves endothelial dysfunction in chronic kidney disease stage 4 patients

Abstract

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 > or =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 x 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 x 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 (beta = 0.63, P < 0.001) and after (beta = 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.

Trial registration: ClinicalTrials.gov NCT00486772.

Figures

Figure 1.

Flow chart of patients enrolled in trial.

Figure 2.

Fetuin-A, high-sensitivity C-reactive protein (hsCRP), and flow-mediated dilation (FMD) levels in calcium acetate and sevelamer groups before and after 8 wk of treatment.

Figure 3.

Scatter plot shows the significant positive relationship between the change in fetuin-A and FMD.