Uremic toxins such as
indoxyl sulfate contribute to the pathogenesis of
chronic kidney disease (CKD) by promoting glomerulosclerosis and interstitial
fibrosis with loss of nephrons and vascular damage.
AST-120, an orally administered intestinal sorbent, adsorbs
indole, a precursor of
indoxyl sulfate, thereby reducing serum and urinary concentrations of
indoxyl sulfate.
AST-120 has been available in Japan since 1991, and subsequently Korea (2005), and the Philippines (2010) as an agent to prolong the time to initiation of
hemodialysis and for improvement of uremic symptoms in patients with CKD. A Medline search was performed to identify data supporting clinical experience with
AST-120 for managing CKD. Prospective open-label and double-blind trials as well as retrospective analyses were included. In prospective trials and retrospective analyses,
AST-120 has been shown to prolong the time to initiation of
hemodialysis, and slow decline in glomerular filtration rate and the increase serum
creatinine. In an initial randomized, double-blind, placebo-controlled trial in the United States,
AST-120 was associated with a significant dose-dependent reduction in serum
indoxyl sulfate levels and a decrease in
uremia-related malaise. The Evaluating Prevention of Progression in CKD (EPPIC) trials, two double-blind, placebo-controlled trials undertaken in North America/Latin America and Europe, are evaluating the efficacy of
AST-120 for preventing the progression of CKD. The results of the EPPIC trials will further define the role of
AST-120 in this debilitating condition.