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


METHODS
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.
Department of Nephrology, Gülhane School of Medicine, Etlik-Ankara, Turkey.
Kayser
K
Caglar
Mahmut Ilker
MI
Yilmaz
Mutlu
M
Saglam
Erdinc
E
Cakir
Cengizhan
C
Acikel
Tayfun
T
Eyileten
Mujdat
M
Yenicesu
Yusuf
Y
Oguz
Abdulgaffar
A
Vural
Juan Jesus
JJ
Carrero
Jonas
J
Axelsson
Bengt
B
Lindholm
Peter
P
Stenvinkel
D000085:Acetates / Q000008:administration & dosage / Q000009:adverse effects; D000328:Adult; D001798:Blood Proteins / Q000378:metabolism*; D002097:C-Reactive Protein / Q000378:metabolism; D002114:Calcinosis / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism; D002118:Calcium / Q000097:blood; D017610:Calcium Compounds / Q000008:administration & dosage / Q000009:adverse effects; D002614:Chelating Agents / Q000008:administration & dosage* / Q000009:adverse effects; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism; D006706:Homeostasis / Q000187:drug effects / Q000502:physiology; D006801:Humans; D008875:Middle Aged; D010710:Phosphates / Q000097:blood; D011073:Polyamines / Q000008:administration & dosage* / Q000009:adverse effects; D011446:Prospective Studies; D051436:Renal Insufficiency, Chronic / Q000150:complications* / Q000378:metabolism; D000069603:Sevelamer; D016896:Treatment Outcome; D014652:Vascular Diseases / Q000188:drug therapy* / Q000209:etiology* / Q000378:metabolism; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology; D060749:alpha-2-HS-Glycoprotein
C556354:AHSG protein, human; D000085:Acetates; D001798:Blood Proteins; D017610:Calcium Compounds; D002614:Chelating Agents; D010710:Phosphates; D011073:Polyamines; D060749:alpha-2-HS-Glycoprotein; D002097:C-Reactive Protein; D000069603:Sevelamer; D002118:Calcium; C120662:calcium acetate