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Abstract: FR-PO122

Superiority of ACF-TEI, a Novel Uremic Toxin Adsorbent, to Classical Oral Adsorbent in In Vitro and In Vivo Adsorption Profiles

Session Information

Category: CKD (Non-Dialysis)

  • 1903 CKD (Non-Dialysis): Mechanisms

Authors

  • Shirakura, Takashi, TEIJIN Pharma Limited, Hino, Tokyo, Japan
  • Shimoyama, Hiroshi, TEIJIN Pharma Limited, Hino, Tokyo, Japan
  • Nishiwaki, Yasumi, TEIJIN Pharma Limited, Hino, Tokyo, Japan
  • Hase, Kumiko, TEIJIN Pharma Limited, Hino, Tokyo, Japan
  • Takahashi, Yoshimasa, TEIJIN Pharma Limited, Hino, Tokyo, Japan
  • Nomura, Johji, TEIJIN Pharma Limited, Hino, Tokyo, Japan
  • Kobayashi, Tsunefumi, TEIJIN Pharma Limited, Hino, Tokyo, Japan
Background

Uremic toxins (UTs) such as indoxyl sulfate (IS) accumulate in the blood of patients with impaired renal function. Since several observation studies have demonstrated a link between serum UT levels and clinical outcomes, UTs have much attention as key factors in the progression of chronic kidney diseases (CKDs) and cardiovascular diseases. Spherical activated carbon (AST-120) adsorbs UTs and those precursors such as indole in the intestinal tract and excretes them out of the body with feces, leading to reduce serum UT levels. Therefore AST-120 is effective in improving symptoms of uremia and delaying the introduction to dialysis in CKD patients. However, the oral adsorbents comprising AST-120 have insufficient adsorption performance and need to be taken at high daily doses. To improve their compliance and efficacy, we focused on activated carbon fiber (ACF) and have identified a novel and potent oral UT adsorbent, ACF-TEI. In this study, we analyzed in vitro adsorption profiles of ACF-TEI and compared in vivo efficacy of ACF-TEI and AST-120 on serum IS levels. We also evaluated the effects of ACF-TEI on renal fibrosis in rat model of kidney injury.

Methods

As for the in vitro adsorption profiles, we examined the adsorption of precursors including indole and p-cresol, and digestive enzymes. In in vivo studies, we compared the effects of ACF-TEI and AST-120 on serum IS concentrations in rat model of CKD and dog model treated with tryptophan, a precursor of indole. To evaluate the effects on renal fibrosis, cisplatin-induced nephrotoxicity (CDDP) model were used.

Results

Compared with AST-120, ACF-TEI showed more potent capacity and speed in adsorbing the UT precursors. ACF-TEI had a low capacity to adsorb digestive enzymes and the capacity was comparable to that of AST-120. In rats and dogs, ACF-TEI reduced serum IS levels more potent than AST-120. ACF-TEI decreased serum and renal IS levels, urinary excretion of KIM-1, and a-SMA expression in CDDP model.

Conclusion

The adsorption capacity and efficiency of ACF-TEI were superior to AST-120. In addition, ACF-TEI reduced the serum IS levels more potent than AST-120 in in vivo models. Thus, ACF-TEI is expected to show more beneficial effects than AST-120 in clinical.