Review of the efficacy of AST-120 (KREMEZIN^®) on renal function in chronic kidney disease patients

Abstract

AST-120 (KREMEZIN®) consists of oral, spherical carbon particles that adsorb uremic toxins and their precursors within the gastrointestinal tract, allowing them to be excreted in the feces. Uremic toxins such as indoxyl sulfate and p-cresyl sulfate are abundant in the blood of chronic kidney disease (CKD) patients and are related to the progression of both CKD and cardiovascular disease. AST-120 was approved in Japan in 1991 followed by Korea (2004), Taiwan (2007) and the Philippines (2010) for treating uremic symptoms and prolonging the time to initiation of dialysis in patients with progressive CKD. In this review, we provide an overview of the past clinical data on AST-120 from 1982 to 2013. The effect of AST-120 for renal events was not supported in the primary analysis of randomized clinical trials. However, post-hoc analyses revealed significant differences between the AST-120 and control groups in the second Japanese phase III trial and in the multinational Evaluating Prevention of Progression in CKD (EPPIC) trials. Furthermore, inhibitory effects on the progression of CKD, as represented by amelioration in the estimated glomerular filtration rate (eGFR) decline and serum creatinine (sCr) elevation were suggested. These results suggest that AST-120 delays the decline in renal function. In addition, AST-120 may prolong the time to the initiation of dialysis, especially in patients with progressive CKD. For further verification of the clinical efficacy of AST-120, future study inclusion criteria should be determined carefully, defining progressive CKD using markers such as declines in eGFR and sCr elevation.

Indoxyl sulfate and high-density lipoprotein cholesterol in early stages of chronic kidney disease

“…This negative correlation exits between IS and HDL-c independent of GFR. Thus clinically, methods to reduce serum IS level (e.g., avoidance of hypervolemia induced microbiome and intestinal permeability changes, and use of uremic toxin adsorbent such as the oral charcoal adsorbent AST-120 [44,45]) might improve HDL-c metabolic disorder. Detailed mechanisms need to be further investigated.…”

Inflammation and Premature Ageing in Chronic Kidney Disease

“…Conversely, the inhibition of uremic toxins should have beneficial effects on ageing markers. As an example drug, the oral sorbent AST-120 adsorbs uremic toxins and their precursors within the gastrointestinal tract [56]. AST-120 dose-dependently decreases circulating indoxyl sulfate [56] and was, therefore, tested in several clinical trials [56].…”

“…As an example drug, the oral sorbent AST-120 adsorbs uremic toxins and their precursors within the gastrointestinal tract [56]. AST-120 dose-dependently decreases circulating indoxyl sulfate [56] and was, therefore, tested in several clinical trials [56]. Results of these trials were heterogenous depending on the prespecified primary endpoints, follow-up period, as well as baseline characteristics of the included subjects.…”

Gut-Derived Protein-Bound Uremic Toxins

“…A number of preclinical and randomized controlled studies have tested this strategy and results are mixed, with clinical and post-hoc analyses showing toxin reductions [ 159 , 160 , 161 ] and others, particularly the primary randomized controlled trial, showing no proof of utility for CKD [ 162 , 163 ]. Regardless, AST-120 has been approved for CKD treatment in Korea, Taiwan, and the Philippines, and is believed to prolong the time to the initiation of dialysis [ 161 ]. Phosphate binders like sevelamer and nicotinamide that sequester phosphate in the GI tract, are believed to improve inflammatory status and may enhance the clearance of uremic toxins.…”