Kidney Week

Abstract: SA-PO0422

Neuroimmune Regulation via the Cholinergic Anti-Inflammatory Pathway Mitigates Peritoneal Injury Induced by Inflammation and High-Salt Stress in Peritoneal Dialysis

Session Information

• Home Dialysis: Science and Cases, from Lab to Living Room
  November 08, 2025 | Location: Exhibit Hall, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Dialysis

• 802 Dialysis: Home Dialysis and Peritoneal Dialysis

Authors

• Umene, Ryusuke, Department of Physiology of Visceral Function and Body Fluid, Graduate School ofBiomedical Sciences, Nagasaki University, Nagasaki, Japan

Ryusuke Umene, MD, PhD

• Washimine, Norito, Department of Physiology of Visceral Function and Body Fluid, Graduate School ofBiomedical Sciences, Nagasaki University, Nagasaki, Japan

Norito Washimine, MD

• Wu, Chia-Hsien, Department of Physiology of Visceral Function and Body Fluid, Graduate School ofBiomedical Sciences, Nagasaki University, Nagasaki, Japan

Chia-Hsien Wu, PhD

• Nakamura, Yasuna, Department of Physiology of Visceral Function and Body Fluid, Graduate School ofBiomedical Sciences, Nagasaki University, Nagasaki, Japan

Yasuna Nakamura, MD, PhD

• Nishino, Tomoya, Department of Nephrology, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan

Tomoya Nishino, MD, PhD

• Inoue, Tsuyoshi, Department of Physiology of Visceral Function and Body Fluid, Graduate School ofBiomedical Sciences, Nagasaki University, Nagasaki, Japan

Tsuyoshi Inoue, MD, PhD

Background

Peritoneal dysfunction remains a major limitation of long-term peritoneal dialysis (PD), often exacerbated by inflammation and fibrosis. Acute bacterial peritonitis and chronic high salt exposure both exacerbate peritoneal inflammation, leading to peritoneal dysfunction. However, controlling this inflammation remains challenging, highlighting the need for novel therapeutic strategies. The cholinergic anti-inflammatory pathway (CAP), mediated by vagus nerve and α7 nicotinic acetylcholine receptors (α7nAChR) on macrophages, is a promising neuroimmune mechanism modulating inflammation. This study investigated whether CAP activation preserves peritoneal function through the neuroimmune system.

Methods

C57BL/6J mice were subjected to intraperitoneal LPS (10 mg/kg) or received 0.9% saline as drinking water for 4 weeks. CAP was activated via nicotine or GTS-21 (α7nAChR agonist). Peritoneal inflammation was assessed by ELISA (TNF-α protein) and qPCR (Tnf, Il1b, Tgfb1 mRNA). Macrophage polarization (Nos2, Arg1) and peritoneal function (D/P creatinine via PET) were evaluated.
In vitro, RAW264.7 (macrophages), MeT-5A (mesothelial cells), and NIH/3T3 (fibroblasts) were stimulated with LPS or NaCl (+20, +40, +60 mM). α7nAChR agonists were applied, and inflammatory and fibrotic gene expression was analyzed by qPCR and ELISA.

Results

In vivo, both LPS and high salt increased TNF-α, Tnf, Il1b, and Tgfb1 levels. CAP activation suppressed these markers, reduced Nos2 and increased Arg1 expression, and significantly lowered D/P creatinine, indicating improved peritoneal transport function.
In vitro, α7nAChR agonists reduced TNF-α in RAW264.7 cells, TNF and IL-6 in MeT-5A cells, and Col1a1 and Tgfb1 in NIH/3T3 fibroblasts. These findings support two CAP-mediated protective pathways: (1) anti-inflammatory macrophage modulation and (2) direct suppression of mesothelial cell activation.

Conclusion

CAP activation preserves peritoneal function in PD by targeting both immune and structural cell compartments under infectious and salt-induced stress. These dual mechanisms highlight CAP as a promising therapeutic target for prolonging peritoneal membrane viability in long-term PD.

Digital Object Identifier (DOI)

• doi: 10.1681/ASN.2025t30qx8m7