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Kidney Week

Abstract: TH-PO290

Excessive Salt Intake Increases Peritoneal Local Production of Interleukin-6 and Baseline Peritoneal Solute Transport Rate in Subtotal Nephrectomized Mice

Session Information

Category: Dialysis

  • 703 Dialysis: Peritoneal Dialysis

Authors

  • Ito, Yasuhiko, Aichi Medical University, Nagakute, Aichi, Japan
  • Sun, Ting, Nagoya University, Nagoya, Japan
  • Suzuki, Yasuhiro, Nagoya University, Nagoya, Japan
  • Tawada, Mitsuhiro, Nagoya University, Nagoya, Japan
  • Nobata, Hironobu, Aichi Medical University, Nagakute, Aichi, Japan
  • Kinashi, Hiroshi, Aichi Medical University, Nagakute, Aichi, Japan
  • Yamaguchi, Makoto, Aichi Medical University, Nagakute, Aichi, Japan
  • Katsuno, Takayuki, Aichi Medical University, Nagakute, Aichi, Japan
  • Maruyama, Shoichi, Nagoya University, Nagoya, Japan
  • Mizuno, Masashi, Nagoya University, Nagoya, Japan
Background

Baseline peritoneal permeability varies between patients before exposure to peritoneal dialysis fluid. Dialysate interleukin (IL)-6 was an indicator of peritoneal transport function. Besides, we previously reported upregulation of peritoneal IL-6 level in uremic mice with salt loading. The present study aims to investigate the peritoneal transport and the role of IL-6 in uremic mice with salt loading.

Methods

Sham-operated (Sham) and subtotal nephrectomized (Nx) mice were randomly given tap water or 1% salt (NaCl)-containing water. After 8 weeks, 4.25% glucose-based peritoneal equilibration test was performed to evaluate peritoneal function. Locally overexpressed IL-6 was functionally blocked by rat anti mouse IL-6 receptor antibody (MR16-1) in another study to examine the role of IL-6 in this process.

Results

A significant elevation of D/P Cr and a decrease of D/D0 glucose were observed in Nx+salt group. There was also enhanced angiogenesis and macrophage infiltration in the peritoneum of Nx+salt mice, along with elevated VEGF-A and MCP-1 concentration in the dialysate. Compared to Nx+water group, the increased concentration of effluent but not serum IL-6 and soluble IL-6 receptor α suggested a strong local production in Nx+salt group. IL-6 was expressed in mesothelial cell layer and CD68-positive macrophages in peritoneum of Nx+salt mice. Elevation of peritoneal phosphorylated stat3 indicated an increment of IL-6 signaling. Blockade of IL-6 signaling by MR16-1 alleviated macrophage infiltration and angiogenesis as well as rescued peritoneal transport function in Nx+salt mice. In mesothelial cells, incubation with additional 40mM NaCl in the medium upregulated the expression of IL-6, along with the translocation into the nucleus of transcription factor tonicity-responsive enhancer binding protein (TonEBP), the only known transcription factor responding to high tonicity. Upregulation of IL-6 under hypertonicity induced by NaCl was also observed in mouse peritoneal-derived macrophages and bone marrow-derived M1 macrophages.

Conclusion

These findings suggest that high salt intake under uremic condition could increase peritoneal local IL-6 production leading to higher peritoneal solute transport rate.