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.
Highlights
Mortality rates among cardiovascular and chronic kidney disease (CKD) patients are very high, which may be related to the high disease burden and inadequate quality of CKD therapy [1]
Recent reports indicate that when renal function deteriorates, oxidative stress induced by excessive uremic toxins can lead to enhanced expression of DNA methyltransferase (DNMT) proteases, which results in hyper-methylation and alternative splicing of the Klotho gene, causing it to lose its physiological function [38]
These results suggested that continuous usage of AST-120 may be beneficial to chronic renal failure patients before the dialysis stage [113]
Summary
Mortality rates among cardiovascular and chronic kidney disease (CKD) patients are very high, which may be related to the high disease burden and inadequate quality of CKD therapy [1]. Administering probiotics during CKD is an alternative method to attenuate the conversion of amino acids to IS and PCS. Active charcoal is another oral adsorbent, which is a nonspecific binder for organic toxins [11]. The study observed end-stage renal disease (ESRD) patients (over 80 years of age) who hesitated to start dialysis; they were prescribed a combination treatment of a very low protein diet and oral activated charcoal (15 g twice daily). A low protein diet and oral activated charcoal may be an alternative therapeutic method for ESRD patients aged above 80 years [12]. We will discuss many basic and clinical aspects of the uremic toxins, IS and PCS, and administration of AST-120 in CKD patients
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