Nakayama Masaaki, Watanabe Kimio, Hayashi Yoshimitsu, Terawaki Hiroyuki, Zhu Wan-Jun, Kabayama Shigeru, Ito Sadayoshi
Contrib Nephrol. 2018;196:162-170. doi: 10.1159/000485717. Epub 2018 Jul 24.
Improved biocompatibility of peritoneal dialysis solution (PDS) is crucial for peritoneal membrane preservation, thereby ensuring long-term peritoneal dialysis (PD) and preventing encapsulating peritoneal sclerosis. We previously reported the protective effect of molecular hydrogen (H2) on mesothelial cells from PDS in nonuremic rats.
In the present study, we examined the effect of H2-containing PDS (commercially available neutral pH type) regarding the protection of peritoneal tissue in experimental chronic kidney disease rats. Furthermore, we conducted a 2-week clinical trial in which H2-containing PDS was used in place of standard PDS and its feasibility was examined. In the experimental study, test solutions were injected through the subcutaneous port into the abdomen for 3 weeks. Histological study revealed a significant increase in the number of mesothelial cells and a significant decrease in peritoneal thickness in the H2-PD group as compared to the control and PD groups. Also, results of immunostaining analysis revealed increased vimentin and apoptotic cells in the membrane of the PD group, indicating that H2 may play a role in ameliorating PDS-induced peritoneal injury and preserving peritoneal integrity. In the clinical trial with 6 prevalent PD patients, all subjects completed the study with no adverse effects. Moreover, there were substantial changes in surrogate markers, such as increased CA125 and mesothelin, in the effluent in selected cases, suggesting enhanced mesothelial regeneration by H2. Key Message: H2-enriched PDS is a candidate novel PDS with improved biocompatibility. Further, our results support the significance of H2-PD clinical trials in the future.
改善腹膜透析液（PDS）的生物相容性对于保护腹膜至关重要，从而确保长期腹膜透析（PD）并预防包裹性腹膜硬化。我们之前报道了分子氢（H2）对非尿毒症大鼠PDS诱导的间皮细胞的保护作用。
在本研究中，我们研究了含H2的PDS（市售中性pH型）对实验性慢性肾脏病大鼠腹膜组织的保护作用。此外，我们进行了一项为期2周的临床试验，用含H2的PDS替代标准PDS，并检验其可行性。在实验研究中，将测试溶液通过皮下端口注入腹部，持续3周。组织学研究显示，与对照组和PD组相比，H2-PD组间皮细胞数量显著增加，腹膜厚度显著降低。此外，免疫染色分析结果显示PD组腹膜中波形蛋白和凋亡细胞增加，表明H2可能在减轻PDS诱导的腹膜损伤和维持腹膜完整性方面发挥作用。在6例维持性PD患者的临床试验中，所有受试者均完成研究，且无不良反应。此外，在部分病例的腹透液中，替代标志物有显著变化，如CA125和间皮素增加，提示H2可促进间皮细胞再生。关键信息：富H2的PDS是一种具有改善生物相容性的新型PDS候选产品。此外，我们的结果支持未来H2-PD临床试验的重要性。
