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Abstract: FR-PO603

Protective Effect of an Oral Adsorbent AST-120 on Podocyte Injury

Session Information

Category: Diabetes

  • 501 Diabetes Mellitus and Obesity: Basic - Experimental

Authors

  • Aoki, Rieko, KUREHA CORPORATION, Tokyo, Japan
  • Fujieda, Ayako, KUREHA CORPORATION, Tokyo, Japan
  • Ezawa, Atsuko, KUREHA CORPORATION, Tokyo, Japan
  • Iijima, Hiroko, KUREHA CORPORATION, Tokyo, Japan
  • Yamashita, Yusuke, KUREHA CORPORATION, Tokyo, Japan
  • Kikuchi, Kaori, KUREHA CORPORATION, Tokyo, Japan
  • Kato, Mariko, KUREHA CORPORATION, Tokyo, Japan
  • Itoh, Yoshiharu, KUREHA CORPORATION, Tokyo, Japan
Background

Diabetic nephropathy is a major complication of diabetes and the leading cause of end-stage renal disease. An oral adsorbent AST-120 has been used clinically in Japan as a medicine for patients with chronic kidney disease (CKD) to slow down the progression of CKD. However, there is little evidence to support therapeutic efficacy of AST-120 for early stage overt diabetic nephropathy. Previously, we showed that the administration of AST-120 reduced the proteinuria and suppressed podocyte foot process effacement on SHR/NDmcr-cp (SHR/ND) rats, rodent model of metabolic syndrome/ type 2 diabetes. We also showed that AST-120 prevented the decrease of renal function and suppressed the levels of serum uremic toxins in unilateral nephrectomized (UNX) SHR/ND rats.
In this study, we investigated whether the renal tissues of UNX SHR/ND rats were ameliorated by the administration of AST-120 and whether uremic toxins induced deleterious effects on the cultured podocyte cells in vitro.

Methods

Male SHR/ND rats, aged 8 weeks, underwent either UNX (n=20) or sham (n=6) surgery under anesthesia. Half of UNX rats were administered 8% AST-120 for 30 weeks in their diet, and serum and 24-hour urine samples were collected for biomedical studies. The gene expression of podocyte markers and fibrosis makers by real-time PCR in renal tissues from UNX-SHR/ND rats treated with or without AST-120. In vitro study, we evaluated effects of uremic toxins on the cytotoxicity and reactive oxygen species (ROS) production of mouse podocyte cells.

Results

AST-120-administered UNX-SHR/ND rats showed significantly lower levels of urinary protein excretion, serum creatinine, serum uremic toxins such as indole acetic acid (IAA) and kidney weight than UNX-SHR/ND rats. Nephrin, as a podocyte marker, in renal tissues was higher expressed in AST-120-administered UNX-SHR/ND rats than in UNX-SHR/ND rats. Plasminogen activator inhibitor-1 was lower expressed in AST-120-administered UNX SHR/ND rats. In vitro study, indoxy sulfate (IS) and IAA induced ROS production and the cytotoxicity of mouse podocyte cells, and N-acetyl-L-cysteine inhibited this effect.

Conclusion

These results indicate that the administration of AST-120 from the early stage of diabetic nephropathy has renoprotective effects. One of the mechanisms of the effect may be the reduction of uremic toxin by AST-120.