Department of Nephrology and Renal Replacement Therapy, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Department of Nephrology and Rheumatology, Aichi Medical University, Nagakute, Japan.
Nephrol Dial Transplant. 2019 Dec 1;34(12):2031-2042. doi: 10.1093/ndt/gfz045.
High peritoneal transport is associated with high mortality and technical failure in peritoneal dialysis (PD). Baseline peritoneal solute transport rate (PSTR) as measured by the peritoneal equilibration test (PET) within 6 months after PD initiation varies between patients. Sodium is reported to be stored in the skin or muscle of dialysis patients. This study investigated whether excessive salt intake in uremic mice caused peritoneal alterations without exposure to PD fluid.
Sham-operated (Sham) and subtotal nephrectomized (Nx) mice were randomly given tap water or 1% sodium chloride (NaCl)-containing water for 8 weeks. PET was then performed to evaluate peritoneal function. Human mesothelial cell line Met-5A was used for in vitro studies.
We observed higher PSTR in Nx mice with 1% NaCl-containing drinking water (Nx + salt) compared with those with tap water (Nx + water), along with enhanced angiogenesis and inflammation in the peritoneum. Blockade of interleukin (IL)-6 signaling rescued peritoneal transport function in Nx + salt mice. In cultured Met-5A, additional NaCl in the medium upregulated IL-6 as well as vascular endothelial growth factor-A, associated with increased expression and nuclear translocation of tonicity-responsive enhancer binding protein (TonEBP). Knockdown of TonEBP lowered the induction caused by high tonicity. Peritoneal TonEBP expression was higher in Nx + salt mice, while removal of high-salt diet lowered TonEBP level and improved peritoneal transport function.
Excessive dietary salt intake caused peritoneal membrane functional and structural changes under uremic status. TonEBP regulated hypertonicity-related inflammatory changes and might play a crucial role in high baseline peritoneal transport.
高腹膜转运与腹膜透析（PD）中的高死亡率和技术失败相关。在 PD 开始后 6 个月内通过腹膜平衡试验（PET）测量的基础腹膜溶质转运率（PSTR）在患者之间有所不同。据报道，钠储存在透析患者的皮肤或肌肉中。本研究旨在调查尿毒症小鼠中过量的盐摄入是否在没有暴露于 PD 液的情况下引起腹膜改变。
假手术（Sham）和部分肾切除（Nx）小鼠被随机给予自来水或含 1%氯化钠（NaCl）的水 8 周。然后进行 PET 以评估腹膜功能。用人间皮细胞系 Met-5A 进行体外研究。
我们观察到，与饮用自来水（Nx+水）的 Nx 小鼠相比，饮用含 1%NaCl 饮用水（Nx+盐）的 Nx 小鼠的 PSTR 更高，同时腹膜中的血管生成和炎症增强。阻断白细胞介素（IL）-6 信号转导可挽救 Nx+盐小鼠的腹膜转运功能。在培养的 Met-5A 中，培养基中额外的 NaCl 上调了 IL-6 和血管内皮生长因子-A，与张力反应增强子结合蛋白（TonEBP）的表达和核转位增加有关。TonEBP 的敲低降低了高渗透压引起的诱导。Nx+盐小鼠的腹膜 TonEBP 表达更高，而去除高盐饮食可降低 TonEBP 水平并改善腹膜转运功能。
在尿毒症状态下，过量的饮食盐摄入可引起腹膜膜功能和结构改变。TonEBP 调节高渗透压相关的炎症变化，可能在高基础腹膜转运中起关键作用。
