Oral Charcoal Adsorbents Attenuate Neointima Formation of Arteriovenous Fistulas.

Yu-Chung Shih,Chih-Cheng Wu,Shen-Chih Wang,Po-Hsun Huang,Jun-Yang Liou,Der-Cherng Tarng

doi:10.3390/toxins12040237

Abstract

Chronic kidney disease (CKD) accelerates the development of neointima formation at the anastomosis site of arteriovenous (AV) fistulas. Accumulation of certain uremic toxins has a deleterious effect on the cardiovascular system. The oral charcoal adsorbent, AST-120, reduces circulating and tissue uremic toxins, but its effect on neointima formation at an AV fistula is unknown. To understand the effect of CKD and AST-120 on neointima formation, we created AV fistulas (common carotid artery to the external jugular vein in an end-to-side anastomosis) in mice with and without CKD. AST-120 was administered in chow before and after AV fistula creation. Administration of AST-120 significantly decreased serum indoxyl sulfate levels in CKD mice. CKD mice had a larger neointima area than non-CKD mice, and administration of AST-120 in CKD mice attenuated neointima formation. Both smooth muscle cell and fibrin components were increased in CKD mice, and AST-120 decreased both. RNA expression of MMP-2, MMP-9, TNFα, and TGFβ was increased in neointima tissue of CKD mice, and AST-120 administration neutralized the expression. Our results provided in vivo evidence to support the role of uremic toxin-binding therapy on the prevention of neointima formation. Peri-operative AST-120 administration deserves further investigation as a potential therapy to improve AV fistula patency.

Highlights

Arteriovenous (AV) fistula dysfunction, such as stenosis and thrombosis, is a major cause of morbidity and mortality among hemodialysis patients
Native AV fistulas are the best vascular access of choice owing to the low incidence of stenosis, thrombosis, or infection as compared to prosthetic grafts or central vein catheters
AV fistulas are usually created for end-stage renal disease (ESRD) patients for the maintenance of hemodialysis

Summary

Introduction

Arteriovenous (AV) fistula dysfunction, such as stenosis and thrombosis, is a major cause of morbidity and mortality among hemodialysis patients. Native AV fistulas are the best vascular access of choice owing to the low incidence of stenosis, thrombosis, or infection as compared to prosthetic grafts or central vein catheters. AV fistulas are usually created for end-stage renal disease (ESRD) patients for the maintenance of hemodialysis. In addition to inflammation and oxidative stress, compelling evidence suggests that the uremic milieu itself plays a critical role in the development of vascular diseases. Indoxyl sulfate (IS), p-cresyl sulfate (PCS), and indole-3 acetic acid are common uremic toxins and have been implicated in a variety of vascular dysfunction [6]. The impact of these uremic toxins on AV fistula stenosis or thrombosis has not been extensively investigated

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