Yonsei Med J.  2016 Jul;57(4):942-949. 10.3349/ymj.2016.57.4.942.

AST-120 Improves Microvascular Endothelial Dysfunction in End-Stage Renal Disease Patients Receiving Hemodialysis

• Ryu JH
• Yu M
• Lee S
• Ryu DR
• Kim SJ
• Kang DH
• Choi KB

• KMID: 2374127
• DOI: http://doi.org/10.3349/ymj.2016.57.4.942

Abstract

PURPOSE
Endothelial dysfunction (ED) is a pivotal phenomenon in the development of cardiovascular disease (CVD) in patients receiving hemodialysis (HD). Indoxyl sulfate (IS) is a known uremic toxin that induces ED in patients with chronic kidney disease. The aim of this study was to investigate whether AST-120, an absorbent of IS, improves microvascular or macrovascular ED in HD patients.
MATERIALS AND METHODS
We conducted a prospective, case-controlled trial. Fourteen patients each were enrolled in respective AST-120 and control groups. The subjects in the AST-120 group were treated with AST-120 (6 g/day) for 6 months. Microvascular function was assessed by laser Doppler flowmetry using iontophoresis of acetylcholine (Ach) and sodium nitroprusside (SNP) at baseline and again at 3 and 6 months. Carotid arterial intima-media thickness (cIMT) and flow-mediated vasodilation were measured at baseline and 6 months. The Wilcoxon rank test was used to compare values before and after AST-120 treatment.
RESULTS
Ach-induced iontophoresis (endothelium-dependent response) was dramatically ameliorated at 3 months and 6 months in the AST-120 group. SNP-induced response showed delayed improvement only at 6 months in the AST-120 group. The IS level was decreased at 3 months in the AST-120 group, but remained stable thereafter. cIMT was significantly reduced after AST-120 treatment. No significant complications in patients taking AST-120 were reported.
CONCLUSION
AST-120 ameliorated microvascular ED and cIMT in HD patients. A randomized study including a larger population will be required to establish a definitive role of AST-120 as a preventive medication for CVD in HD patients.

Keyword

AST-120; hemodialysis; microvascular circulation; endothelial dysfunction; laser-Doppler flowmetry; indoxyl sulfate

MeSH Terms

Acetylcholine
Adult
Carbon/*therapeutic use
Cardiovascular Diseases/etiology/*prevention & control
Carotid Intima-Media Thickness
Endothelium, Vascular/*physiopathology
Female
Humans
Iontophoresis
Kidney Failure, Chronic/complications/*physiopathology/*therapy
Laser-Doppler Flowmetry
Male
Microcirculation/physiology
Middle Aged
Nitroprusside
Oxides/*therapeutic use
Prospective Studies
*Renal Dialysis
Young Adult
Acetylcholine
Carbon
Nitroprusside
Oxides

Figure

• 

  Fig. 1 Changes in microcirculatory vascular dysfunction assessed by iontophoresis with LDF between control and AST-120 groups. (A) The acetylcholine (Ach)-induced response was significantly improved after both 3 months (M) and 6 M of AST-120 treatment compared to baseline, but was worsened in the control group. (B) The nitroprusside (NSP)-induced response was not different for either 3 M or 6 M of AST-120 treatment. Vascular response was described as the ratio of perfusion units of responsive flow compared with basal flow. *p=0.005 vs. iontophoresis of 0 M, †p=0.001 vs. iontophoresis of 0 M.

• 

  Fig. 2 Comparison of macrocirculatory vascular dysfunction assessed by brachial flow-mediated vasodilation between the control and AST-120 groups. Both endothelium-dependent vasodilation (A) and endothelium-independent vasodilation (B) were not significantly changed in either group after 6 months compared to baseline.

• 

  Fig. 3 Changes in carotid intima-media thickness (cIMT) between the control and AST-120 groups. cIMT was significantly reduced after 6 months in the AST-120 treatment group.*p<0.01 vs. cIMT at baseline.

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