Received July 12, 2007
Accepted on October 18, 2007

ORIGINAL ARTICLES

Short-Term Treatment with Sevelamer Increases Serum Fetuin-A Concentration and Improves Endothelial Dysfunction in Chronic Kidney Disease Stage 4 Patients

Kayser Caglar ^*, Mahmut Ilker Yilmaz ^*||1, Mutlu Saglam , Erdinc Cakir , Cengizhan Acikel , Tayfun Eyileten ^*, Mujdat Yenicesu ^*, Yusuf Oguz ^*, Abdulgaffar Vural ^*, Juan Jesus Carrero ^||, Jonas Axelsson ^||, Bengt Lindholm ^||, and Peter Stenvinkel ^||

Departments of *Nephrology, Radiology, Biochemistry, Epidemiology, Gülhane School of Medicine, Etlik-Ankara, Turkey; and ||Division of Renal Medicine and Baxter Novum, Department of Clinical Science, Karolinska Institutet, Karolinska University Hospital, Huddinge, Stockholm, Sweden

¹ To whom correspondence should be addressed. E-mail: mahmutiyilmaz{at}yahoo.com.

	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 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 ( = 0.63, P < 0.001) and after ( = 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.