Effects of AST-120 on Blood Concentrations of Protein-Bound Uremic Toxins and Biomarkers of Cardiovascular Risk in Chronic Dialysis Patients

Abstract

Background: Removal of protein-bound uremic toxins by dialysis therapy is limited. The effect of oral adsorbent AST-120 in chronic dialysis patients has rarely been investigated. Methods: AST-120 was administered 6.0 g/day for 3 months in 69 chronic dialysis patients. The blood concentrations of indoxyl sulfate, p-cresol sulfate and biomarkers of cardiovascular risk were determined before and after AST-120 treatment. Results: AST-120 significantly decreased both the total and free forms of indoxyl sulfate and p-cresol sulfate ranging from 21.9 to 58.3%. There were significant simultaneous changes of the soluble tumor necrosis factor-like weak inducer of apoptosis (sTWEAK, 24% increase), malondialdehyde (14% decrease) and interleukin-6 (19% decrease). A significant association between the decrease of indoxyl sulfate and changes of sTWEAK and interleukin-6 was noted. Conclusions: AST-120 effectively decreased indoxyl sulfate and p-cresol sulfate levels in both total and free forms. AST-120 also improved the profile of cardiovascular biomarkers.

Indoxyl Sulfate Induces IL-6 Expression in Vascular Endothelial and Smooth Muscle Cells through OAT3-Mediated Uptake and Activation of AhR/NF-κB Pathway

“…AST-120 was administered 6.0 g/day for 3 months in dialysis patients, and significantly decreased serum levels of IS and IL-6 [24]. Thus, the present findings that IS induces IL-6 production in vascular cells might explain the suppressive effects of AST-120 on serum IL-6 levels.…”

Gut Microbiota-Dependent Trimethylamine N -Oxide (TMAO) Pathway Contributes to Both Development of Renal Insufficiency and Mortality Risk in Chronic Kidney Disease

“…For example, lactobacillus acidophilus or bifidobacterium have been reported to reduce inflammatory signaling associated with the microbiota-derived metabolites that accumulate in CKD 36–39 , in addition to modestly improving renal function 40, 41 . Similarly, prebiotic compound use to interrupt pathways that lead to gut microbiota derived uremic toxins such as indoxyl sulfate and p-cresyl sulfate has shown some efficacy in both human and animal trials of CKD 5, 42 . Further studies are warranted to see whether dietary interventions, or disruption of the meta-organismal pathway involving TMAO production, may retard development of CKD, progression of renal functional impairment among subjects with CKD, and adverse CVD event risks in subjects with CKD.…”

“…Bacterial structural components such as lipopolysaccharide 3 , and metabolites such as indoxyl sulfate, p-cresyl sulfate, amines, and ammonia, have been identified as potential microbial byproducts capable of initiating pro-inflammatory cytokine/chemokine cascades seen in the setting of CKD and end stage renal disease 4 . Thus, it has been hypothesized that gut-microbiota derived uremic toxins may serve as both therapeutic targets and/or assessment tools for renal diseases in this vulnerable population 1, 5–7 . However, demonstration of a role for these uremic toxins in CVD pathogenesis has been indirect.…”

Tryptophan metabolism, its relation to inflammation and stress markers and association with psychological and cognitive functioning: Tasmanian Chronic Kidney Disease pilot study

“…The intestinal absorption of indoles may be reduced by the orally-administered carbon-adsorbent AST-120. Adding this pharmaceutical to the standard therapy of CKD patients showed reduced serum levels of indoxyl sulfate [32, 66], improvement in some of the uraemia symptoms [66] and a decrease in markers for cardiovascular disease [67]. Although clinical trials showed that treatment with AST-120 resulted in more gradual disease progression [66, 68], its overall benefit is yet to be proven [68, 69].…”