Sevelamer, FGF-23 and Endothelial Dysfunction in Chronic Kidney Disease (CKD)
Condition: We Investigated the Relationship Between Plasma FGF23 Levels and Endothelial Dysfunction in a Sizable Series of Incident Stage 3-4 CKD Patients.
Study type: Interventional
Phase: Phase 4

Summary: 
      Vascular calcification and endothelial dysfunction (ED) contribute to the development of
      cardiovascular disease (CVD) in patients with chronic kidney disease (CKD). Sevelamer, a
      non-calcium based phosphate binder, has been shown to attenuate cardiovascular calcification
      in CKD patients while the exact mechanism has not been clarified.

      This study was designed to investigate the effect of short-term sevelamer treatment on both
      serum FGF23 levels concentrations and ED seen in CKD patients.

      The researchers investigated the relationship between plasma FGF23 levels and the forearm
      blood flow response to ischemia in the forearm in a sizable series of incident stage 3-4 CKD
      patients.
    

Detailed description: 
      CKD stage 4 patients older than 18 years of age and willing to participate to the study were
      screened. Those who had serum phosphorus > 5.5 mg/dl were evaluated for the study. Patients
      with diabetes mellitus, history of coronary artery disease, smokers and those taking statins
      or renin-angiotensin blockers were excluded because of the effect of these factors on
      endothelial dysfunction. Of 192 screened patients 100 met the study criteria and were
      included in this study. Thirty-seven healthy subjects were studied as controls. The ethical
      committee of Gulhane School of Medicine approved the study and written informed consent was
      obtained from all patients.

      Study design:

      This was a randomized study conducted from 2008 through 2010 in Gulhane School of Medicine.
      The Outpatient Clinic of Department of Nephrology is a tertiary referral center. At
      admission, most patients were untreated (including phosphate binders) or treated only with
      antihypertensive agents. After the first evaluation, patients receiving phosphate binders
      (n=17) underwent a 2-week washout period. Patients who developed a phosphate level >5.5 mg/dl
      during this period were included in the study. Patients were randomly assigned in 1:1 ratio
      to receive sevelamer (Renagel capsule) or calcium acetate (Phos Ex tablet). The treatment
      phase was 8 weeks. During the study period serum calcium and phosphorus concentration were
      measured every 2 weeks and the dose of phosphate binders were titrated to achieve a serum
      phosphorus concentration < 5.5 mg/dl. The starting dose for sevelamer was 1-2 capsules (800
      mg) three times a day and for calcium acetate (1000 mg) 1 tablet three times a day. The
      medications were given with meal and the doses were increased as needed. Patients were not
      given calcitriol during the study period.

      Fasting blood samples were taken before and after the study to measure serum creatinine,
      serum albumin, hs-CRP, insulin, 25 (OH) Vit D, iPTH, lipid profile and serum FGF-23
      concentration. Additionally, flow-mediated dilatation (FMD) and Intima Media Thickness (IMT)
      were also evaluated before and after the study.
    

Intervention name(s): Sevelamer; calcium acetate
Intervention type(s): Drug; Drug
Intervention description(s): The starting dose for sevelamer was 1-2 capsules (800 mg) three times a day; calcium acetate (1000 mg) 1 tablet three times a day
Intervention MeSH terms: Calcium; Sevelamer; Calcium acetate
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single
Primary purpose: Prevention
Keywords: FGF-23, endothelial dysfunction, sevelamer