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 >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 ؋ PO 4 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 ؋ PO 4 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.

Vascular Toxicity of Phosphate in Chronic Kidney Disease

“…Caglar et al studied 50 nondiabetic, hyperphosphatemic patients at CKD stage 4 and observed that an 8-week course of treatment with sevelamer was associated with less inflammation, higher fetuin-A levels and better endothelial function, compared with calcium acetate. 25 Yilmaz et al for their part recently reported, in a similar cohort, a modulation of FGF23 levels by phosphate binders, independently associated with improvement of endothelial function. 26 …”

Arterial stiffness, vascular calcification and bone metabolism in chronic kidney disease

“…We demonstrated its beneficial effect for arterial stiffness parameters in dialysis patients previously [124] . A recent study in nondiabetic CKD patients demonstrated a significant increase in fetuin-A after treatment with sevelamer [125] . According to these results, sevelamer may attenuate the progression of arterial pathology in CKD, at least partly through the elevation of fetuin-A.…”

Correlation Between Intestinal Colony Numbers and Inflammation Markers (TNF-Alpha, IL-6, High-Sensitive CRP) Following the Use of Sevelamer in Rats with Kidney Failure

“…5/6 nephrectomy was performed under general anesthesia with ligation of one of the extrarenal branches of left renal artery and right nephrectomy. 7 The special food containing high phosphate (P) and high P+ sevelamer were manufactured in MBD Yem Ticaret in Gebze-Kocaeli. Eighteen rats were included in the study and were divided into three groups.…”

“…6 Endothelial dysfunction was shown to be a risk factor in apparently healthy patients for the development of atherosclerosis years before atheromatosis plaques were formed. 7 Furthermore, administration of the sevelamer to maintenance hemodialyis patients is associated with a significant decrease in hs-CRP, IL-6 and serum endotoxin levels. On the other hand, increased translocation of endotoxin to the systemic circulation was shown to be correlated with inflammation in various animal models.…”