Impacts of Indoxyl Sulfate and p-Cresol Sulfate on Chronic Kidney Disease and Mitigating Effects of AST-120

Abstract

Uremic toxins, such as indoxyl sulfate (IS) and p-cresol, or p-cresyl sulfate (PCS), are markedly accumulated in the organs of chronic kidney disease (CKD) patients. These toxins can induce inflammatory reactions and enhance oxidative stress, prompting glomerular sclerosis and interstitial fibrosis, to aggravate the decline of renal function. Consequently, uremic toxins play an important role in the worsening of renal and cardiovascular functions. Furthermore, they destroy the quantity and quality of bone. Oral sorbent AST-120 reduces serum levels of uremic toxins in CKD patients by adsorbing the precursors of IS and PCS generated by amino acid metabolism in the intestine. Accordingly, AST-120 decreases the serum IS levels and reduces the production of reactive oxygen species by endothelial cells, to impede the subsequent oxidative stress. This slows the progression of cardiovascular and renal diseases and improves bone metabolism in CKD patients. Although large-scale studies showed no obvious benefits from adding AST-120 to the standard therapy for CKD patients, subsequent sporadic studies may support its use. This article summarizes the mechanisms of the uremic toxins, IS, and PCS, and discusses the multiple effects of AST-120 in CKD patients.

Oral Charcoal Adsorbents Attenuate Neointima Formation of Arteriovenous Fistulas

“…Our study demonstrated that adsorbents of uremic toxins administered in the perioperative period could attenuate neointima formation and improve patency of AV fistula. AST-120 was developed in 1982 as an oral carbonaceous adsorbent for the binding of IS and PCS precursors in the gastrointestinal tract [38]. It could effectively decrease serum IS and PCS levels in CKD patients without major side effects.…”

Measurement of gut microbial metabolites in cardiometabolic health and translational research

“…40 Both indoxyl sulfate and FIGURE 1 Crosstalk between gut microbial metabolites and organs beyond the gut through the gut-systemic axis ↑foam cell formation, ↓reverse cholesterol transport, ↑platelet aggregation potential. Target receptor remains unknown 33,34 Indoxyl sulfate Tryptophan Uremic toxin proposed to aggravate chronic renal disease, CVD, as well as CKD related bone disorders 21,35 Enter proximal renal tubular cell through organic anion transporter and cause oxidative stress by activating ROS system 21,35 p-Cresol sulfate Tyrosine, phenylalanine…”

“…Uremic toxin ↑cardiovascular mortality in CKD patients. Elevated in urine of colorectal cancer patients 21,36 Exhibits genotoxicity, cytotoxicity in vitro and induces renal interstitial fibrosis and glomerulosclerosis in mice model 21,36 Indolepropionic acid Tryptophan Negatively correlated with low-grade inflammation and type II diabetes mellitus development. Potential antituberculosis effect [37][38][39] Bind to pregame X receptor in intestinal cells and improve mucosal homeostasis and gut barrier function [37][38][39] Imidazole 18 Phytochemicals from plant foods can also be modified by gut microbiota to produce compounds with higher levels of bioactivity.…”

“…These small bioactive molecules, such as short‐chain fatty acids (SCFAs), trimethylamine N ‐oxide (TMAO), imidazole propionate, conjugated linoleic acid, and s‐equol, are derived mainly from the gut microbiota metabolism of dietary components such as dietary fibers, amino acids, fatty acids, and phytochemicals . Studies have suggested that gut microbiota‐derived metabolites play key roles in health maintenance and disease progression . They may also serve as novel biomarkers in clinical diagnosis and prognosis .…”

“…[15][16][17][18][19] Studies have suggested that gut microbiotaderived metabolites play key roles in health maintenance and disease progression. [20][21][22] They may also serve as novel biomarkers in clinical diagnosis and prognosis. [23][24][25] In this article, we discuss and highlight some of the most important literature about the mass spectrometrybased analysis of gut microbial metabolites and their relationships to translational research for future clinical applications.…”