Pharmacological actions of indoxyl sulfate and ast-120 that should be recognized for the strategic treatment of patients with chronic kidney disease

Abstract

Although there are many uremic substances in the body, the most studied and well-known molecule that predominantly binds to plasma proteins is indoxyl sulfate (IS). Many research groups have reported IS to have toxic effects on the kidney and cardiovascular system. It is difficult to remove IS with regular hemodialysis or hemodiafiltration. On the other hand, AST-120 has the capacity to bind to indole, which is a precursor of IS in the intestinal tract and excrete it in feces. IS production in the liver is efficiently suppressed by AST-120 administration. However, large-scale clinical studies have not shown that AST-120 suppresses hard endpoints such as doubling serum creatinine, end-stage renal disease, and death. In patients with accelerated chronic kidney disease (CKD) progression, AST-120 is expected to suppress those hard renal endpoints, but only when compliance to treatment is high. It is necessary to validate the renal protective effect of AST-120, as expected from the basic study on IS, including more patients with slowly progressive CKD in a large-scale clinical study in the future.