Abstract: TH-PO420

ACF-TEI, a Novel Oral Adsorbent, Shows Potent Adsorption Effect on Uremic Toxin in the Rat Model and the System Mimicked Human Gastrointestinal Tract

Session Information

Category: Nutrition, Inflammation, and Metabolism

  • 1401 Nutrition, Inflammation, Metabolism

Authors

  • Shimoyama, Hiroshi, Teijin Pharma Limited, Tokyo, Japan
  • Nishiwaki, Yasumi, Teijin Pharma Limited, Tokyo, Japan
  • Murakami, Takashi, Teijin Pharma Limited, Tokyo, Japan
  • Takahashi, Yoshimasa, Teijin Pharma Limited, Tokyo, Japan
  • Kobayashi, Tsunefumi, Teijin Pharma Limited, Tokyo, Japan
Background

Uremic toxins (UTs), such as indoxyl sulfate (IS) and p-cresyl sulfate (PCS), accumulate in the blood of patients with impaired renal function. Since several studies have demonstrated a link between serum UTs levels and clinical outcomes, they draw much attention as key factors in the progression of chronic kidney diseases (CKDs) and cardiovascular diseases. Thus, adsorbing UTs in the intestinal tract and excreting with feces is effective for inhibiting the progression of CKDs and delaying the introduction of dialysis treatment. We have identified a novel oral UTs adsorbent, ACF-TEI, which has more potent adsorption profiles to UTs than existing adsorbents. In this study, we examined in vitro adsorption capacities of ACF-TEI to several UTs and the reducing effect of ACF-TEI on serum UTs in CKD model rats. In addition, to estimate the effectiveness of ACF-TEI in human, we evaluated the effect of ACF-TEI on UT adsorption in a system that mimicked human gastrointestinal (GI) tract.

Methods

ACF-TEI was mixed with solutions of indole, the precursor of IS produced by enterobacteria, or other UTs and reacted, then the adsorption capacity was calculated. ACF-TEI was administered orally to bilateral nephrectomized rats, and then concentrations of serum IS and PCS were measured. Adsorption of indole in the human GI tract was estimated using dynamic multi-compartmental GI tract model.

Results

ACF-TEI showed higher adsorption capacity to indole and other UTs than existing adsorbent. In the bilateral nephrectomized rats, ACF-TEI dose-dependently reduced serum IS and PCS levels and the effects were more potent than the existing adsorbents. In the dynamic multi-compartmental GI tract model, ACF-TEI reduced colonic indole concentration at lower doses than the existing adsorbents.

Conclusion

ACF-TEI adsorbed various UTs and showed the potent effects not only in the rodent model but also in the human GI tract mimicked system. Therefore, in clinical, ACF-TEI is expected to show potent UTs reducing effect and to be beneficial for patients with CKDs.