Kidney Week

Abstract: SA-PO0276

Renoprotective Mechanisms via Parasympathetic Nervous System Stimulation in Cisplatin-Induced AKI

Session Information

• AKI: Mechanisms - Cell Signaling
  October 24, 2026 | Location: Exhibit Hall A, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Acute Kidney Injury

• 103 AKI: Mechanisms

Authors

• Ashizawa, Kanoko, Nagasaki Daigaku Daigakuin Ishiyakugaku Sogo Kenkyuka, Nagasaki, Nagasaki Prefecture, Japan

Kanoko Ashizawa, MD

• Umene, Ryusuke, Nagasaki Daigaku Daigakuin Ishiyakugaku Sogo Kenkyuka, Nagasaki, Nagasaki Prefecture, Japan

Ryusuke Umene, MD, PhD

• Washimine, Norito, Nagasaki Daigaku Daigakuin Ishiyakugaku Sogo Kenkyuka, Nagasaki, Nagasaki Prefecture, Japan

Norito Washimine, MD

• Wu, Chia-Hsien, Nagasaki Daigaku Daigakuin Ishiyakugaku Sogo Kenkyuka, Nagasaki, Nagasaki Prefecture, Japan

Chia-Hsien Wu, PhD

• Nakamura, Yasuna, Nagasaki Daigaku Daigakuin Ishiyakugaku Sogo Kenkyuka, Nagasaki, Nagasaki Prefecture, Japan

Yasuna Nakamura, MD, PhD

• Nishino, Tomoya, Nagasaki Daigaku Daigakuin Ishiyakugaku Sogo Kenkyuka, Nagasaki, Nagasaki Prefecture, Japan

Tomoya Nishino, MD, PhD

• Inoue, Tsuyoshi, Nagasaki Daigaku Daigakuin Ishiyakugaku Sogo Kenkyuka, Nagasaki, Nagasaki Prefecture, Japan

Tsuyoshi Inoue, MD, PhD

Group or Team Name

• Department of Nephrology

Background

Acute kidney injury (AKI) increases the risks of chronic kidney disease, cardiovascular diseases, and mortality. Cisplatin is a widely used chemotherapeutic agent and causes AKI in approximately 30% of treated patients, which leads to treatment discontinuation. However, effective therapies for cisplatin-induced AKI remain lacking. Recently, the anti-inflammatory and renoprotective effects mediated by the parasympathetic nervous system have gained attention. While the cholinergic anti-inflammatory pathway mediated by α7 nicotinic acetylcholine receptors (α7nAChR) on macrophages has been established, direct renoprotective pathways in the kidney remain poorly understood. This study aims to clarify the renoprotective effects of direct renal parasympathetic stimulation in cisplatin-induced AKI.

Methods

Nicotine (a nicotinic acetylcholine receptor agonist) was administered to wild-type and proximal tubule-specific α7nAChR knockout (KO) mice in a cisplatin-induced AKI model. Renal function, tubular injury markers, inflammatory cytokine expression of kidney tissues, and histological findings were evaluated. RNA sequencing of whole kidneys was performed in wild-type mice across four groups with or without cisplatin and nicotine treatment. In vitro, HK-2 (human proximal tubular epithelial cell line) cells were treated with cisplatin and GTS-21 (selective α7nAChR agonist), and tubular injury markers, inflammatory cytokines, and nuclear factor-κB (NF-κB) nuclear translocation were assessed.

Results

Nicotine attenuated cisplatin-induced AKI in wild-type mice, as evidenced by reduced plasma creatinine levels, tubular injury markers, inflammatory cytokine expression, and histological damage. In contrast, these effects tended to be diminished in KO mice. RNA sequencing analysis revealed upregulation of amino acid metabolism-related genes by nicotine. In HK-2 cells, GTS-21 reduced cisplatin-induced expression of tubular injury markers and inflammatory cytokines, and suppressed NF-κB nuclear translocation.

Conclusion

These findings suggest that parasympathetic nervous system stimulation directly activates renal α7nAChRs and protects against cisplatin-induced AKI. The protective effects may involve improved amino acid metabolism and suppression of NF-κB pathway activation. Further studies are required to clarify the underlying mechanisms and develop novel therapeutic strategies.