Shirai Yoko, Miura Kenichiro, Ike Takeshi, Sasaki Kensuke, Ishizuka Kiyonobu, Horita Shigeru, Taneda Sekiko, Hirano Daishi, Honda Kazuho, Yamaguchi Yutaka, Masaki Takao, Hattori Motoshi
Department of Pediatric Nephrology, Tokyo Women's Medical University, Tokyo, Japan.
Department of Nephrology, Hiroshima University Hospital, Hiroshima, Japan.
Kidney Int Rep. 2022 Sep 3;7(11):2431-2445. doi: 10.1016/j.ekir.2022.08.013. eCollection 2022 Nov.
Neutral-pH dialysate has been reported to be beneficial to prevent the peritoneal pathological changes in adult peritoneal dialysis (PD) patients, but its use is controversial in pediatric PD patients. In addition, the impact of cumulative dialytic glucose exposure has not been examined.
Pediatric PD patients using conventional fluids (conventional group, = 31) or those using neutral-pH fluids (neutral-pH group, = 33) were compared. Clinical risk factors for peritoneal pathological changes in the neutral-pH group were analyzed using generalized linear modeling. Furthermore, the mechanisms of peritoneal pathological changes were explored using immunohistochemical studies and cultured cells.
The median (interquartile range) duration of dialysis was 3.2 (1.7-5.3) years in overall patients. After propensity score matching, the conventional group showed increased thickening of the submesothelial compact (SMC) zone and lower luminal-to-vessel diameter (L/V) ratio than the neutral-pH group. In the neutral-pH group, the cumulative dialytic glucose exposure was an independent risk factor for greater thickness of the SMC zone (odds ratio [OR], 1.54; 95% confidence interval [CI], 1.16-2.05) and higher submesothelial microvessel density (OR, 1.29; 95% CI, 1.01-1.64). Immunohistochemical study showed that cumulative dialytic glucose exposure correlated with the proportion of the tissue expressing hypoxia inducible factor -1α (HIF-1α) and vascular endothelial growth factor-α (VEGF-α). In human peritoneal mesothelial cells, high glucose significantly increased HIF-1α and VEGF-α expressions.
Cumulative dialytic glucose exposure is an independent risk factor for peritoneal fibrosis and angiogenesis in pediatric patients undergoing PD using neutral-pH fluids, which might be associated with greater VEGF-α production by myofibroblasts implying a hypoxic response.
据报道，中性pH值透析液有助于预防成年腹膜透析（PD）患者的腹膜病理改变，但在儿科PD患者中其使用存在争议。此外，累积透析葡萄糖暴露的影响尚未得到研究。
比较使用传统透析液的儿科PD患者（传统组，n = 31）和使用中性pH值透析液的患者（中性pH值组，n = 33）。使用广义线性模型分析中性pH值组腹膜病理改变的临床危险因素。此外，通过免疫组织化学研究和培养细胞探索腹膜病理改变的机制。
总体患者的透析中位（四分位间距）时间为3.2（1.7 - 5.3）年。倾向得分匹配后，传统组与中性pH值组相比，其间皮下致密（SMC）区增厚增加，管腔与血管直径（L/V）比值降低。在中性pH值组中，累积透析葡萄糖暴露是SMC区厚度增加（优势比[OR]，1.54；95%置信区间[CI]，1.16 - 2.05）和间皮下微血管密度升高（OR，1.29；95% CI，1.01 - 1.64）的独立危险因素。免疫组织化学研究表明，累积透析葡萄糖暴露与表达缺氧诱导因子-1α（HIF-1α）和血管内皮生长因子-α（VEGF-α）的组织比例相关。在人腹膜间皮细胞中，高糖显著增加HIF-1α和VEGF-α表达。
对于使用中性pH值透析液的儿科PD患者，累积透析葡萄糖暴露是腹膜纤维化和血管生成的独立危险因素，这可能与肌成纤维细胞产生更多VEGF-α有关，提示存在缺氧反应。
